Sample records for platelet plug formation

  1. Frictional Fluid Dynamics and Plug Formation in Multiphase Millifluidic Flow (United States)

    Dumazer, Guillaume; Sandnes, Bjørnar; Ayaz, Monem; Mâløy, Knut Jørgen; Flekkøy, Eirik Grude


    We study experimentally the flow and patterning of a granular suspension displaced by air inside a narrow tube. The invading air-liquid interface accumulates a plug of granular material that clogs the tube due to friction with the confining walls. The gas percolates through the static plug once the gas pressure exceeds the pore capillary entry pressure of the packed grains, and a moving accumulation front is reestablished at the far side of the plug. The process repeats, such that the advancing interface leaves a trail of plugs in its wake. Further, we show that the system undergoes a fluidization transition—and complete evacuation of the granular suspension—when the liquid withdrawal rate increases beyond a critical value. An analytical model of the stability condition for the granular accumulation predicts the flow regime.

  2. Microstructure Formation and Degradation Mechanism of Cementitious Plugging Agent Slurries

    Institute of Scientific and Technical Information of China (English)

    YAN Peiyu; ZHOU Yongxiang; YANG Zhenjie; QIN Jian


    The hydration products and microstructure of class G oil well cement and a newly developed plugging agent (YLD) slurries cured in the simulated temperature and pressure environment, which was of similar temperature and pressure with those at the bottom of oil well in a normal depth, were investigated using XRD, TG and SEM. Severe leakage is confirmed at the interface between hardened slurries and steel tube during the dynamically curing process, which induces the quick loss of cementing property of slurries. This should be the dominating cause of degradation of class G oil well cement slurry. A secondary hydration process can take place at the eroded interface of hardened YLD plugging agent slurry. Newly formed C-S-H gel has a self-healing effect to repair the damaged interface, which unceasingly maintains the cementing property of the YLD plugging agent slurry. Therefore, the effective using period of YLD plugging agent can be prolonged.

  3. Platelet proteomics. (United States)

    Zufferey, Anne; Fontana, Pierre; Reny, Jean-Luc; Nolli, Severine; Sanchez, Jean-Charles


    Platelets are small cell fragments, produced by megakaryocytes, in the bone marrow. They play an important role in hemostasis and diverse thrombotic disorders. They are therefore primary targets of antithrombotic therapies. They are implicated in several pathophysiological pathways, such as inflammation or wound repair. In blood circulation, platelets are activated by several pathways including subendothelial matrix and thrombin, triggering the formation of the platelet plug. Studying their proteome is a powerful approach to understand their biology and function. However, particular attention must be paid to different experimental parameters, such as platelet quality and purity. Several technologies are involved during the platelet proteome processing, yielding information on protein identification, characterization, localization, and quantification. Recent technical improvements in proteomics combined with inter-disciplinary strategies, such as metabolomic, transcriptomics, and bioinformatics, will help to understand platelets biological mechanisms. Therefore, a comprehensive analysis of the platelet proteome under different environmental conditions may contribute to elucidate complex processes relevant to platelet function regarding bleeding disorders or platelet hyperreactivity and identify new targets for antiplatelet therapy.

  4. Plug-in to Eclipse environment for VHDL source code editor with advanced formatting of text (United States)

    Niton, B.; Pozniak, K. T.; Romaniuk, R. S.


    The paper describes an idea and realization of a smart plug-in to the Eclipse software environment. The plug-in is predicted for editing of the VHDL source code. It extends considerably the capabilities of the VEditor program, which bases on the open license. There are presented the results of the formatting procedures performed on chosen examples of the VHDL source codes. The work is a part of a bigger project of building smart programming environment for design of advanced photonic and electronic systems. The examples of such systems are quoted in references.

  5. Glycoprotein Ibα clustering in platelet storage and function

    NARCIS (Netherlands)

    Gitz, E.


    Platelets are anucleated, discoid-shaped cells that play an essential role in the formation of a hemostatic plug to prevent blood loss from injured vessels. Initial platelet arrest at the damaged arterial vessel wall is mediated through the interaction between the platelet receptor glycoprotein (GP)

  6. Glycoprotein Ibα clustering in platelet storage and function

    NARCIS (Netherlands)

    Gitz, E.


    Platelets are anucleated, discoid-shaped cells that play an essential role in the formation of a hemostatic plug to prevent blood loss from injured vessels. Initial platelet arrest at the damaged arterial vessel wall is mediated through the interaction between the platelet receptor glycoprotein (GP)

  7. Experimental investigation of gas hydrate formation, plugging and transportability in partially dispersed and water continuous systems (United States)

    Vijayamohan, Prithvi

    As oil/gas subsea fields mature, the amount of water produced increases significantly due to the production methods employed to enhance the recovery of oil. This is true especially in the case of oil reservoirs. This increase in the water hold up increases the risk of hydrate plug formation in the pipelines, thereby resulting in higher inhibition cost strategies. A major industry concern is to reduce the severe safety risks associated with hydrate plug formation, and significantly extending subsea tieback distances by providing a cost effective flow assurance management/safety tool for mature fields. Developing fundamental understanding of the key mechanistic steps towards hydrate plug formation for different multiphase flow conditions is a key challenge to the flow assurance community. Such understanding can ultimately provide new insight and hydrate management guidelines to diminish the safety risks due to hydrate formation and accumulation in deepwater flowlines and facilities. The transportability of hydrates in pipelines is a function of the operating parameters, such as temperature, pressure, fluid mixture velocity, liquid loading, and fluid system characteristics. Specifically, the hydrate formation rate and plugging onset characteristics can be significantly different for water continuous, oil continuous, and partially dispersed systems. The latter is defined as a system containing oil/gas/water, where the water is present both as a free phase and partially dispersed in the oil phase (i.e., entrained water in the oil). Since hydrate formation from oil dispersed in water systems and partially dispersed water systems is an area which is poorly understood, this thesis aims to address some key questions in these systems. Selected experiments have been performed at the University of Tulsa flowloop to study the hydrate formation and plugging characteristics for the partially dispersed water/oil/gas systems as well as systems where the oil is completely dispersed

  8. A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models. (United States)

    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


    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.

  9. New gene functions in megakaryopoiesis and platelet formation (United States)

    Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O’Reilly, Paul F.; Shin, So-Youn; Esko, Tõnu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, François; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amélie; Cambien, François; Chambers, John C.; Cucca, Francesco; D’Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Döring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kühnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Leach, Irene Mateo; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nöthlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Tönjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Völker, Uwe; Wichmann, H.-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole


    Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. PMID:22139419

  10. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles (United States)

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


    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.

  11. Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII. (United States)

    Mattheij, Nadine J A; Swieringa, Frauke; Mastenbroek, Tom G; Berny-Lang, Michelle A; May, Frauke; Baaten, Constance C F M J; van der Meijden, Paola E J; Henskens, Yvonne M C; Beckers, Erik A M; Suylen, Dennis P L; Nolte, Marc W; Hackeng, Tilman M; McCarty, Owen J T; Heemskerk, Johan W M; Cosemans, Judith M E M


    Coated platelets, formed by collagen and thrombin activation, have been characterized in different ways: i) by the formation of a protein coat of α-granular proteins; ii) by exposure of procoagulant phosphatidylserine; or iii) by high fibrinogen binding. Yet, their functional role has remained unclear. Here we used a novel transglutaminase probe, Rhod-A14, to identify a subpopulation of platelets with a cross-linked protein coat, and compared this with other platelet subpopulations using a panel of functional assays. Platelet stimulation with convulxin/thrombin resulted in initial integrin α(IIb)β3 activation, the appearance of a platelet population with high fibrinogen binding, (independently of active integrins, but dependent on the presence of thrombin) followed by phosphatidylserine exposure and binding of coagulation factors Va and Xa. A subpopulation of phosphatidylserine-exposing platelets bound Rhod-A14 both in suspension and in thrombi generated on a collagen surface. In suspension, high fibrinogen and Rhod-A14 binding were antagonized by combined inhibition of transglutaminase activity and integrin α(IIb)β3 Markedly, in thrombi from mice deficient in transglutaminase factor XIII, platelet-driven fibrin formation and Rhod-A14 binding were abolished by blockage of integrin α(IIb)β3. Vice versa, star-like fibrin formation from platelets of a patient with deficiency in α(IIb)β3(Glanzmann thrombasthenia) was abolished upon blockage of transglutaminase activity. We conclude that coated platelets, with initial α(IIb)β3 activation and high fibrinogen binding, form a subpopulation of phosphatidylserine-exposing platelets, and function in platelet-dependent star-like fibrin fiber formation via transglutaminase factor XIII and integrin α(IIb)β3.

  12. Novel aspects of platelet aggregation

    Directory of Open Access Journals (Sweden)

    Roka-Moya Y. M.


    Full Text Available The platelet aggregation is an important process, which is critical for the hemostatic plug formation and thrombosis. Recent studies have shown that the platelet aggregation is more complex and dynamic than it was previously thought. There are several mechanisms that can initiate the platelet aggregation and each of them operates under specific conditions in vivo. At the same time, the influence of certain plasma proteins on this process should be considered. This review intends to summarize the recent data concerning the adhesive molecules and their receptors, which provide the platelet aggregation under different conditions.

  13. In-vitro model for the ultrastructural study of the formation of thrombi in human platelets. (United States)

    Cerecedo, Doris; González, Sirenia; Mondragón, Mónica; Reyes, Elba; Mondragón, Ricardo


    Platelets are cell fragments with dynamic properties involved in clot formation after tissue damage. Platelet activation causes a change in shape, secretion of intracellular granules and aggregation with each other through the cytoskeleton components and biochemical changes. Platelet adhesion, considered as the major event in haemostasis, has been studied in several in-vitro and in-vivo models to evaluate the feasible thrombogenicity of some materials, the dynamics of specific receptors, as well as the effect of different buffers and inhibitors in this process. In spite of the numerous reports about platelet activation, to date there is no information available about the fine structure of the platelet-platelet and platelet-substrate interactions. In the present report we describe an in-vitro system that allows the visualization of these interactions: platelets are adhered to an inert substrate, and interactions with suspended platelets as a process to initiate the formation of thrombi was followed by ultramicrotomy and transmission electron microscopy.

  14. Platelets (United States)

    ... tiny fraction of the blood volume. The principal function of platelets is to prevent bleeding. Red blood cells are ... forming a long string. This illustrates the basic function of platelets, to stick to any foreign surface and then ...

  15. Inherited platelet disorders and oral health. (United States)

    Valera, Marie-Cécile; Kemoun, Philippe; Cousty, Sarah; Sie, Pierre; Payrastre, Bernard


    Platelets play a key role in thrombosis and hemostasis. Accumulation of platelets at the site of vascular injury is the first step in the formation of hemostatic plugs, which play a pivotal role in preventing blood loss after injury. Platelet adhesion at sites of injury results in spreading, secretion, recruitment of additional platelets, and formation of platelet aggregates. Inherited platelet disorders are rare causes of bleeding syndromes, ranging from mild bruising to severe hemorrhage. The defects can reflect deficiency or dysfunction of platelet surface glycoproteins, granule contents, cytoskeletal proteins, platelet pro-coagulant function, and signaling pathways. For instance, Bernard-Soulier syndrome and Glanzmann thrombasthenia are attributed to deficiencies of glycoprotein Ib/IX/V and GPIIb/IIIa, respectively, and are rare but severe platelet disorders. Inherited defects that impair platelet secretion and/or signal transduction are among the most common forms of mild platelet disorders and include gray platelet syndrome, Hermansky-Pudlak syndrome, and Chediak-Higashi syndrome. When necessary, desmopressin, antifibrinolytic agents, and transfusion of platelets remain the most common treatment of inherited platelet disorders. Alternative therapies such as recombinant activated factor VII are also available for a limited number of situations. In this review, we will discuss the management of patients with inherited platelet disorders in various clinical situations related to dental cares, including surgical intervention. © 2012 John Wiley & Sons A/S.

  16. In vitro platelet activation, aggregation and platelet-granulocyte complex formation induced by surface modified single-walled carbon nanotubes. (United States)

    Fent, János; Bihari, Péter; Vippola, Minnamari; Sarlin, Essi; Lakatos, Susan


    Surface modification of single-walled carbon nanotubes (SWCNTs) such as carboxylation, amidation, hydroxylation and pegylation is used to reduce the nanotube toxicity and render them more suitable for biomedical applications than their pristine counterparts. Toxicity can be manifested in platelet activation as it has been shown for SWCNTs. However, the effect of various surface modifications on the platelet activating potential of SWCNTs has not been tested yet. In vitro platelet activation (CD62P) as well as the platelet-granulocyte complex formation (CD15/CD41 double positivity) in human whole blood were measured by flow cytometry in the presence of 0.1mg/ml of pristine or various surface modified SWCNTs. The effect of various SWCNTs was tested by whole blood impedance aggregometry, too. All tested SWCNTs but the hydroxylated ones activate platelets and promote platelet-granulocyte complex formation in vitro. Carboxylated, pegylated and pristine SWCNTs induce whole blood aggregation as well. Although pegylation is preferred from biomedical point of view, among the samples tested by us pegylated SWCNTs induced far the most prominent activation and a well detectable aggregation of platelets in whole blood.

  17. Novel mouse hemostasis model for real-time determination of bleeding time and hemostatic plug composition (United States)



    Summary Introduction Hemostasis is a rapid response by the body to stop bleeding at sites of vessel injury. Both platelets and fibrin are important for the formation of a hemostatic plug. Mice have been used to uncover the molecular mechanisms that regulate the activation of platelets and coagulation under physiologic conditions. However, measurements of hemostasis in mice are quite variable, and current methods do not quantify platelet adhesion or fibrin formation at the site of injury. Methods We describe a novel hemostasis model that uses intravital fluorescence microscopy to quantify platelet adhesion, fibrin formation and time to hemostatic plug formation in real time. Repeated vessel injuries of ~ 50–100 μm in diameter were induced with laser ablation technology in the saphenous vein of mice. Results Hemostasis in this model was strongly impaired in mice deficient in glycoprotein Ibα or talin-1, which are important regulators of platelet adhesiveness. In contrast, the time to hemostatic plug formation was only minimally affected in mice deficient in the extrinsic tissue factor (TFlow) or the intrinsic factor IX coagulation pathways, even though platelet adhesion was significantly reduced. A partial reduction in platelet adhesiveness obtained with clopidogrel led to instability within the hemostatic plug, especially when combined with impaired coagulation in TFlow mice. Conclusions In summary, we present a novel, highly sensitive method to quantify hemostatic plug formation in mice. On the basis of its sensitivity to platelet adhesion defects and its real-time imaging capability, we propose this model as an ideal tool with which to study the efficacy and safety of antiplatelet agents. PMID:25442192

  18. 2-Arachidonoylglycerol enhances platelet formation from human megakaryoblasts. (United States)

    Gasperi, Valeria; Avigliano, Luciana; Evangelista, Daniela; Oddi, Sergio; Chiurchiù, Valerio; Lanuti, Mirko; Maccarrone, Mauro; Valeria Catani, Maria


    Platelets modulate vascular system integrity, and their loss is critical in haematological pathologies and after chemotherapy. Therefore, identification of molecules enhancing platelet production would be useful to counteract thrombocytopenia. We have previously shown that 2-arachidonoylglycerol (2-AG) acts as a true agonist of platelets, as well as it commits erythroid precursors toward the megakaryocytic lineage. Against this background, we sought to further interrogate the role of 2-AG in megakaryocyte/platelet physiology by investigating terminal differentiation, and subsequent thrombopoiesis. To this end, we used MEG-01 cells, a human megakaryoblastic cell line able to produce in vitro platelet-like particles. 2-AG increased the number of cells showing ruffled surface and enhanced surface expression of specific megakaryocyte/platelet surface antigens, typical hallmarks of terminal megakaryocytic differentiation and platelet production. Changes in cytoskeleton modeling also occurred in differentiated megakaryocytes and blebbing platelets. 2-AG acted by binding to CB1 and CB2 receptors, because specific antagonists reverted its effect. Platelets were split off from megakaryocytes and were functional: they contained the platelet-specific surface markers CD61 and CD49, whose levels increased following stimulation with a natural agonist like collagen. Given the importance of 2-AG for driving megakaryopoiesis and thrombopoiesis, not surprisingly we found that its hydrolytic enzymes were tightly controlled by classical inducers of megakaryocyte differentiation. In conclusion 2-AG, by triggering megakaryocyte maturation and platelet release, may have clinical efficacy to counteract thrombocytopenia-related diseases.

  19. Defective PDI release from platelets and endothelial cells impairs thrombus formation in Hermansky-Pudlak syndrome. (United States)

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


    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.

  20. Instability and the formation of bubbles and the plugs in fluidized beds

    Directory of Open Access Journals (Sweden)

    Piotr Schulz


    Full Text Available This is an review paper, particulary concentrate on results not many researches by reason that are explain in the text. We consider stability of disperse, two-phase flow (gas-solid particles or liquid-solid particles linear and non-linear. In particular we discuss the result of Anderson, Sundareson and Jackson (1995 [Anderson K., Sundareson S., Jackson R.: Instabilities and the formation of bubbles in fluidized beds. J. Fluid Mech. 303 (1995, 327-366] that for vertical dispersion flow one- and two-dimensional, they attack problem growing disturbances directly by numerical integration of equations of motion from given initial conditions (using computer Cray C-90. In principle, this would allow authors to explore all aspects of dynamical behaviour of fluidized beds. It is interesting mechanism of periodic plug describing by Anderson et al. and attest by other researchers. Second part of paper is more general, dedicate the problem of linear stability of uniformly fluidized state ("fluidized bed". We make the most important stages of calculations (after to Jackson (2000 [Jackson R.: The Dynamics of Fluidized Particles. Cambridge University Press 2000] and demonstrate that the majority (but not all of fluidized beds with parameters having technical importance is unstable, or stable in narrow interval of wave numbers \\(k\\.

  1. Comparison of coronary artery specific leukocyte-platelet conjugate formation in unstable versus stable angina pectoris. (United States)

    Patel, Parag B; Pfau, Steven E; Cleman, Michael W; Brennan, Joseph J; Howes, Christopher; Remetz, Michael; Cabin, Henry S; Setaro, John F; Rinder, Henry M


    This study evaluates transcoronary changes in neutrophil and platelet activation and conjugate formation in patients with angina pectoris secondary to coronary artery disease. We examined parameters of neutrophil and platelet activation as well as the neutrophil-platelet conjugate formation in patients who underwent diagnostic coronary angiography. Thirty-nine patients with chest pain referred for cardiac catheterization were studied (23 patients with unstable angina pectoris [UAP] and 16 with stable angina pectoris [SAP]). Before coronary angiography, blood samples were obtained simultaneously from the aortic root and coronary sinus to assess leukocyte (CD11b) and platelet (CD62P) activation and leukocyte-platelet conjugates. There was a 94% increase in CD62-expressing platelets from the aorta to the coronary sinus in patients with UAP compared with a 49% increase in patients with SAP. The percentage of neutrophil-platelet conjugates increased by 22% in patients with UAP compared with a 16% decrease in those with SAP (p <0.01). In contrast, monocyte-platelet binding across the coronary bed increased to a similar degree in both groups. This study demonstrates an increase in neutrophil-platelet conjugates across the coronary circulation in UAP, compatible with a higher activation state in both cell types.

  2. Thioredoxin Inhibitors Attenuate Platelet Function and Thrombus Formation (United States)

    Metcalfe, Clive; Ramasubramoni, Anjana; Pula, Giordano; Harper, Matthew T.; Mundell, Stuart J.; Coxon, Carmen H.


    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

  3. Effect of red blood cells on platelet activation and thrombus formation in tortuous arterioles

    Directory of Open Access Journals (Sweden)

    Jennifer K. W. Chesnutt


    Full Text Available Thrombosis is a major contributor to cardiovascular disease, which can lead to myocardial infarction and stroke. Thrombosis may form in tortuous microvessels, which are often seen throughout the human body, but the microscale mechanisms and processes are not well understood. In straight vessels, the presence of red blood cells (RBCs is known to push platelets toward walls, which may affect platelet aggregation and thrombus formation. However in tortuous vessels, the effects of RBC interactions with platelets in thrombosis are largely unknown. Accordingly, the objective of this work was to determine the physical effects of RBCs, platelet size, and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A discrete element computational model was used to simulate the transport, collision, adhesion, aggregation, and shear-induced platelet activation of hundreds of individual platelets and RBCs in thrombus formation in tortuous arterioles. Results showed that high shear stress near the inner sides of curved arteriole walls activated platelets to initiate thrombosis. RBCs initially promoted platelet activation, but then collisions of RBCs with mural thrombi reduced the amount of mural thrombus and the size of emboli. In the absence of RBCs, mural thrombus mass was smaller in a highly tortuous arteriole compared to a less tortuous arteriole. In the presence of RBCs however, mural thrombus mass was larger in the highly tortuous arteriole compared to the less tortuous arteriole. As well, smaller platelet size yielded less mural thrombus mass and smaller emboli, either with or without RBCs. This study shed light on microscopic interactions of RBCs and platelets in tortuous microvessels, which have implications in various pathologies associated with thrombosis and bleeding.

  4. Effect of Red Blood Cells on Platelet Activation and Thrombus Formation in Tortuous Arterioles. (United States)

    Chesnutt, Jennifer K W; Han, Hai-Chao


    Thrombosis is a major contributor to cardiovascular disease, which can lead to myocardial infarction and stroke. Thrombosis may form in tortuous microvessels, which are often seen throughout the human body, but the microscale mechanisms and processes are not well understood. In straight vessels, the presence of red blood cells (RBCs) is known to push platelets toward walls, which may affect platelet aggregation and thrombus formation. However in tortuous vessels, the effects of RBC interactions with platelets in thrombosis are largely unknown. Accordingly, the objective of this work was to determine the physical effects of RBCs, platelet size, and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A discrete element computational model was used to simulate the transport, collision, adhesion, aggregation, and shear-induced platelet activation of hundreds of individual platelets and RBCs in thrombus formation in tortuous arterioles. Results showed that high shear stress near the inner sides of curved arteriole walls activated platelets to initiate thrombosis. RBCs initially promoted platelet activation, but then collisions of RBCs with mural thrombi reduced the amount of mural thrombus and the size of emboli. In the absence of RBCs, mural thrombus mass was smaller in a highly tortuous arteriole compared to a less tortuous arteriole. In the presence of RBCs however, mural thrombus mass was larger in the highly tortuous arteriole compared to the less tortuous arteriole. As well, smaller platelet size yielded less mural thrombus mass and smaller emboli, either with or without RBCs. This study shed light on microscopic interactions of RBCs and platelets in tortuous microvessels, which have implications in various pathologies associated with thrombosis and bleeding.

  5. Germline variants in ETV6 underlie reduced platelet formation, platelet dysfunction and increased levels of circulating CD34+ progenitors (United States)

    Poggi, Marjorie; Canault, Matthias; Favier, Marie; Turro, Ernest; Saultier, Paul; Ghalloussi, Dorsaf; Baccini, Veronique; Vidal, Lea; Mezzapesa, Anna; Chelghoum, Nadjim; Mohand-Oumoussa, Badreddine; Falaise, Céline; Favier, Rémi; Ouwehand, Willem H.; Fiore, Mathieu; Peiretti, Franck; Morange, Pierre Emmanuel; Saut, Noémie; Bernot, Denis; Greinacher, Andreas; BioResource, NIHR; Nurden, Alan T.; Nurden, Paquita; Freson, Kathleen; Trégouët, David-Alexandre; Raslova, Hana; Alessi, Marie-Christine


    Variants in ETV6, which encodes a transcription repressor of the E26 transformation-specific family, have recently been reported to be responsible for inherited thrombocytopenia and hematologic malignancy. We sequenced the DNA from cases with unexplained dominant thrombocytopenia and identified six likely pathogenic variants in ETV6, of which five are novel. We observed low repressive activity of all tested ETV6 variants, and variants located in the E26 transformation-specific binding domain (encoding p.A377T, p.Y401N) led to reduced binding to corepressors. We also observed a large expansion of megakaryocyte colony-forming units derived from variant carriers and reduced proplatelet formation with abnormal cytoskeletal organization. The defect in proplatelet formation was also observed in control CD34+ cell-derived megakaryocytes transduced with lentiviral particles encoding mutant ETV6. Reduced expression levels of key regulators of the actin cytoskeleton CDC42 and RHOA were measured. Moreover, changes in the actin structures are typically accompanied by a rounder platelet shape with a highly heterogeneous size, decreased platelet arachidonic response, and spreading and retarded clot retraction in ETV6 deficient platelets. Elevated numbers of circulating CD34+ cells were found in p.P214L and p.Y401N carriers, and two patients from different families suffered from refractory anemia with excess blasts, while one patient from a third family was successfully treated for acute myeloid leukemia. Overall, our study provides novel insights into the role of ETV6 as a driver of cytoskeletal regulatory gene expression during platelet production, and the impact of variants resulting in platelets with altered size, shape and function and potentially also in changes in circulating progenitor levels. PMID:27663637

  6. SIRT1 prevents pulmonary thrombus formation induced by arachidonic acid via downregulation of PAF receptor expression in platelets. (United States)

    Kim, Yun Hak; Bae, Jin Ung; Kim, In Suk; Chang, Chulhun L; Oh, Sae Ock; Kim, Chi Dae


    SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin. AA- and PAF-mediated platelet aggregations were suppressed by WEB2086, a PAF receptor (PAFR) antagonist. Pulmonary thrombus formation induced by PAF or AA was also attenuated by WEB2086, suggesting that PAFR plays a key role in AA-induced platelet aggregation. In platelets isolated from SIRT1-TG mice as well as in platelets treated with resveratrol or reSIRT1, PAFR expression was decreased, whereas this expressional downregulation by SIRT1 activators was inhibited in platelets treated with MG132 (a proteasome inhibitor) or NH4Cl (a lysosome inhibitor). Furthermore, platelet aggregation induced by AA was markedly attenuated by resveratrol and reSIRT1. Likewise, the increased pulmonary thrombus formation in mice treated with AA was also attenuated by SIRT1 activators. In line with these results, pulmonary thrombus formation was markedly attenuated in SIRT1-TG mice. Taken together, this study showed that SIRT1 downregulates PAFR expression on platelets via proteasomal and lysosomal pathways, and that this downregulation inhibits platelet aggregation in vitro and pulmonary thrombus formation in vivo.

  7. Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway.

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    Wei Li

    Full Text Available 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 (0.01 μg/ml, 0.1 μg/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.

  8. Mesoscopic Modeling of Thrombus Formation and Growth: Platelet Deposition in Complex Geometries (United States)

    Yazdani, Alireza; Karniadakis, George


    Haemodynamics and blood rheology are important contributing factors to thrombus formation at a vulnerable vessel wall, and adhesion of platelets to a vascular surface, particularly in regions of flow stagnation, recirculation and reattachment is significantly important in formation of thrombi. For example, haemodynamic micro-environment can have effects on thrombosis inside the atherosclerotic plaques and aneurysms. To study these effects, we have developed and validated a model for platelet aggregation in blood flow using Dissipative Particle Dynamics (DPD) method. In this model platelets are considered as single DPD particles interacting with each other via Morse potential once activated. We assign an activation delay time to each platelet such that they remain passive during that time. We investigate the effect of different geometries on platelet aggregation by considering arterial stenosis at different levels of occlusion, and aneurysms of different shapes and sizes. The results show a marked increase in platelet aggregation within the boundaries of deceleration zone by increasing the degree of stenosis. Further, we observe enhanced platelet margination and wall deposition in the presence of red blood cells.

  9. The NLRP3 inflammasome and bruton's tyrosine kinase in platelets co-regulate platelet activation, aggregation, and in vitro thrombus formation. (United States)

    Murthy, Pranav; Durco, Filip; Miller-Ocuin, Jennifer L; Takedai, Teiko; Shankar, Shruthi; Liang, Xiaoyan; Liu, Xiao; Cui, Xiangdong; Sachdev, Ulka; Rath, Dominik; Lotze, Michael T; Zeh, Herbert J; Gawaz, Meinrad; Weber, Alexander N; Vogel, Sebastian


    Cleavage of interleukin-1β (IL-1β) is a key inflammatory event in immune cells and platelets, which is mediated by nucleotide-binding domain leucine rich repeat containing protein (NLRP3)-dependent activation of caspase-1. In immune cells, NLRP3 and caspase-1 form inflammasome complexes with the adaptor proteins apoptosis-associated speck-like protein containing a CARD (ASC) and bruton's tyrosine kinase (BTK). In platelets, however, the regulatory triggers and the functional effects of the NLRP3 inflammasome are unknown. Here, we show in vitro that the platelet NLRP3 inflammasome contributes to platelet activation, aggregation, and thrombus formation. NLRP3 activity, as monitored by caspase-1 activation and cleavage and secretion of IL-1β, was upregulated in activated platelets, which was dependent on platelet BTK. Pharmacological inhibition or genetic ablation of BTK in platelets led to decreased platelet activation, aggregation, and in vitro thrombus formation. We identify a functionally relevant link between BTK and NLRP3 in platelets, with potential implications in disease states associated with abnormal coagulation and inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. New gene functions in megakaryopoiesis and platelet formation

    NARCIS (Netherlands)

    Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Maegi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Goegele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O'Reilly, Paul F.; Shin, So-Youn; Esko, Toenu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, Francois; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amelie; Cambien, Francois; Chambers, John C.; Cucca, Francesco; D'Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Doering, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kuehnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Mateo Leach, Irene; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Noethlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Toenjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Voelker, Uwe; Wichmann, H-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole


    Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a

  11. Retreatment of endodontically failed tooth with wide-open apex using platelet rich fibrin membrane as matrix and an apical plug of Biodentine™

    Directory of Open Access Journals (Sweden)

    Ajinkya Mansing Pawar


    Full Text Available The primary reason for an endodontic failure is the persistence or regrowth of bacteria within the root canal system, and such cases require retreatment. The tooth root development and closure of its apex occurs till 3 years after the eruption. Traumatic injuries during this development period result in endodontic complications. While dealing with a tooth, with an open apex the prime objective was eliminating bacteria from the root canal system with minimum irritation to the periapical tissues and induction of apical closure to produce favorable conditions and to confine the root canal filling within the canal space. Traditionally as supported by literature multiple dressings of calcium hydroxide medicament were advocated to induce apical barrier formation followed by an evolution of the apical artificial barrier technique where the mineral trioxide aggregate (MTA was used. Recently introduced Biodentine™ is similar to MTA with its basic composition, which can be used as its substitute. The main difficulty associated while treating teeth with wide-open apices are preventing the overfilling of the restorative materials that serve as an artificial barrier. Use of a matrix overcomes this challenge. Platelet-rich fibrin (PRF a matrix of autologous fibrin, embedded with a large quantity of platelet and leukocyte cytokines during centrifugation can be successfully used as an apical membrane. The present case, reports a novel procedure of apexification of endodontically failed central incisor with open apex using PRF as apical membrane and Biodentine™.

  12. Platelet-neutrophil complex formation-a detailed in vitro analysis of murine and human blood samples. (United States)

    Mauler, Maximilian; Seyfert, Julia; Haenel, David; Seeba, Hannah; Guenther, Janine; Stallmann, Daniela; Schoenichen, Claudia; Hilgendorf, Ingo; Bode, Christoph; Ahrens, Ingo; Duerschmied, Daniel


    Platelets form complexes with neutrophils during inflammatory processes. These aggregates migrate into affected tissues and also circulate within the organism. Several studies have evaluated platelet-neutrophil complexes as a marker of cardiovascular diseases in human and mouse. Although multiple publications have reported platelet-neutrophil complex counts, we noticed that different methods were used to analyze platelet-neutrophil complex formation, resulting in significant differences, even in baseline values. We established a protocol for platelet-neutrophil complex measurement with flow cytometry in murine and human whole blood samples. In vitro platelet-neutrophil complex formation was stimulated with ADP or PMA. We tested the effect of different sample preparation steps and cytometer settings on platelet-neutrophil complex detection and noticed false-positive counts with increasing acquisition speed. Platelet-neutrophil complex formation depends on platelet P-selectin expression, and antibody blocking of P-selectin consequently prevented ADP-induced platelet-neutrophil complex formation. These findings may help generating more comparable data among different research groups that examine platelet-neutrophil complexes as a marker for cardiovascular disease and novel therapeutic interventions.

  13. Modelling of platelet-fibrin clot formation in flow with a DPD-PDE method. (United States)

    Tosenberger, A; Ataullakhanov, F; Bessonov, N; Panteleev, M; Tokarev, A; Volpert, V


    The paper is devoted to mathematical modelling of clot growth in blood flow. Great complexity of the hemostatic system dictates the need of usage of the mathematical models to understand its functioning in the normal and especially in pathological situations. In this work we investigate the interaction of blood flow, platelet aggregation and plasma coagulation. We develop a hybrid DPD-PDE model where dissipative particle dynamics (DPD) is used to model plasma flow and platelets, while the regulatory network of plasma coagulation is described by a system of partial differential equations. Modelling results confirm the potency of the scenario of clot growth where at the first stage of clot formation platelets form an aggregate due to weak inter-platelet connections and then due to their activation. This enables the formation of the fibrin net in the centre of the platelet aggregate where the flow velocity is significantly reduced. The fibrin net reinforces the clot and allows its further growth. When the clot becomes sufficiently large, it stops growing due to the narrowed vessel and the increase of flow shear rate at the surface of the clot. Its outer part is detached by the flow revealing the inner part covered by fibrin. This fibrin cap does not allow new platelets to attach at the high shear rate, and the clot stops growing. Dependence of the final clot size on wall shear rate and on other parameters is studied.

  14. Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression. (United States)

    Nygaard, Gyrid; Herfindal, Lars; Kopperud, Reidun; Aragay, Anna M; Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune; Selheim, Frode


    In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation.

  15. Cathepsin G-dependent modulation of platelet thrombus formation in vivo by blood neutrophils.

    Directory of Open Access Journals (Sweden)

    Nauder Faraday

    Full Text Available 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.

  16. An investigation on platelet transport during thrombus formation at micro-scale stenosis.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Tovar-Lopez

    Full Text Available This paper reports on an investigation of mass transport of blood cells at micro-scale stenosis where local strain-rate micro-gradients trigger platelet aggregation. Using a microfluidic flow focusing platform we investigate the blood flow streams that principally contribute to platelet aggregation under shear micro-gradient conditions. We demonstrate that relatively thin surface streams located at the channel wall are the primary contributor of platelets to the developing aggregate under shear gradient conditions. Furthermore we delineate a role for red blood cell hydrodynamic lift forces in driving enhanced advection of platelets to the stenosis wall and surface of developing aggregates. We show that this novel microfluidic platform can be effectively used to study the role of mass transport phenomena driving platelet recruitment and aggregate formation and believe that this approach will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation in the context of cardiovascular diseases such as acute coronary syndromes and ischemic stroke.

  17. Blood platelet-derived microparticles release and bubble formation after an open-sea air dive. (United States)

    Pontier, Jean-Michel; Gempp, Emmanuel; Ignatescu, Mihaela


    Bubble-induced platelet aggregation offers an index for evaluating decompression severity in humans and in a rat model of decompression sickness. Endothelial cells, blood platelets, or leukocytes shed microparticles (MP) upon activation and during cell apoptosis. The aim was to study blood platelet MP (PMP) release and bubble formation after a scuba-air dive in field conditions. Healthy, experienced divers were assigned to 1 experimental group (n = 10) with an open-sea air dive to 30 msw for 30 min and 1 control group (n = 5) during head-out water immersion for the same period. Bubble grades were monitored with a pulsed doppler according to Kissman Integrated Severity Score (KISS). Blood samples for platelet count (PC) and PMP (annexin V and CD41) were taken 1 h before and after exposure in both groups. The result showed a decrease in post-dive PC compared with pre-dive values in experimental group with no significant change in the control group. We observed a significant increase in PMP values after the dive while no change was revealed in the control group. There was a significant positive correlation between the PMP values after the dive and the KISS bubble score. The present study highlighted a relationship between the post-dive decrease in PC, platelet MP release, and bubble formation. Release of platelet MPs could reflect bubble-induced platelet aggregation and could play a key role in alteration of the coagulation. Further studies must investigate endothelial and leukocyte MP release in the same field conditions.

  18. Platelet function tests: a comparative review

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    Paniccia R


    Full Text Available Rita Paniccia,1,2 Raffaella Priora,1,2 Agatina Alessandrello Liotta,2 Rosanna Abbate1,2 1Department of Experimental and Clinical Medicine, Thrombosis Center, University of Florence, Florence, Italy; 2Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Abstract: In physiological hemostasis a prompt recruitment of platelets on the vessel damage prevents the bleeding by the rapid formation of a platelet plug. Qualitative and/or quantitative platelet defects promote bleeding, whereas the high residual reactivity of platelets in patients on antiplatelet therapies moves forward thromboembolic complications. The biochemical mechanisms of the different phases of platelet activation – adhesion, shape change, release reaction, and aggregation – have been well delineated, whereas their complete translation into laboratory assays has not been so fulfilled. Laboratory tests of platelet function, such as bleeding time, light transmission platelet aggregation, lumiaggregometry, impedance aggregometry on whole blood, and platelet activation investigated by flow cytometry, are traditionally utilized for diagnosing hemostatic disorders and managing patients with platelet and hemostatic defects, but their use is still limited to specialized laboratories. To date, a point-of-care testing (POCT dedicated to platelet function, using pertinent devices much simpler to use, has now become available (ie, PFA-100, VerifyNow System, Multiplate Electrode Aggregometry [MEA]. POCT includes new methodologies which may be used in critical clinical settings and also in general laboratories because they are rapid and easy to use, employing whole blood without the necessity of sample processing. Actually, these different platelet methodologies for the evaluation of inherited and acquired bleeding disorders and/or for monitoring antiplatelet therapies are spreading and the study of platelet function is strengthening. In this review, well

  19. Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression

    Energy Technology Data Exchange (ETDEWEB)

    Nygaard, Gyrid [Proteomic Unit at University of Bergen (PROBE), University of Bergen, Bergen (Norway); Department of Biomedicine, University of Bergen, Bergen (Norway); Herfindal, Lars; Kopperud, Reidun [Department of Biomedicine, University of Bergen, Bergen (Norway); Aragay, Anna M. [Department of Biomedicine, University of Bergen, Bergen (Norway); Molecular Biology Institute of Barcelona (IBMB, CSIC), Barcelona (Spain); Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune [Department of Biomedicine, University of Bergen, Bergen (Norway); Selheim, Frode, E-mail: [Proteomic Unit at University of Bergen (PROBE), University of Bergen, Bergen (Norway); Department of Biomedicine, University of Bergen, Bergen (Norway)


    Highlights: • We investigated the impact of cyclic nucleotide analogues on platelet activation. • Different time dependence were found for inhibition of platelet activation. • Additive effect was found using PKA- and PKG-activating analogues. • Our results may explain some of the discrepancies reported for cNMP signalling. - Abstract: In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation.

  20. Platelet activation and thrombus formation relates to the presence of myocardial inflammation in patients with cardiomyopathy. (United States)

    Bobbert, Peter; Weikert, Ulf; Schmidt-Lucke, Caroline; Skurk, Carsten; Meyer, Alexander; Steffens, Daniel; Schultheiss, Heinz Peter; Rauch, Ursula


    Patients with cardiomyopathy show a significantly increased risk for thromboembolic events due to a hypercoagulable state and platelet dysfunction. The pathophysiologic mechanism underlying the increasing platelet activity in patients with cardiomyopathy remains unclear. We performed a clinical study to elucidate the link between myocardial tissue alterations and platelet activation in patients with cardiomyopathy. A total of 30 patients with suspected cardiomyopathy and 10 healthy control patients were included in our study. Hemodynamic parameters were measured by catheterization and echocardiography. Endomyocardial biopsies were taken to determine myocardial inflammation. Flow cytometry was performed to examine the platelet activation by quantification of p-selectin and thrombospondin expression on platelets. The p-selectin (8.46 ± 3.67 AU) and thrombospondin (26.56 ± 23.21 AU) expression was significantly correlated with the amount of CD3+ T cells (p-selectin: r=0.573, p<0.05; thrombospondin: r=0.488, p<0.05) and the endothelial/interstitial activation (p-selectin: r=0.521, p<0.05; thrombospondin: r=0.39, p<0.05). This was found to be independent of hemodynamic parameters, age, and gender. The platelet activation of patients (n=3) with echocardiographically documented ventricular thrombi was significantly increased (p-selectin: 12.57 ± 5.5 AU vs. 8.1 ± 3.2 AU, p<0.05) and this was associated with elevated myocardial inflammation scores. Myocardial inflammation is associated with a significant increase in platelet activation and ventricular thrombus formation independently of the hemodynamic conditions. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  1. Suilysin-induced Platelet-Neutrophil Complexes Formation is Triggered by Pore Formation-dependent Calcium Influx (United States)

    Zhang, Shengwei; Zheng, Yuling; Chen, Shaolong; Huang, Shujing; Liu, Keke; Lv, Qingyu; Jiang, Yongqiang; Yuan, Yuan


    Platelet activation and platelet–neutrophil interactions have been found to be involved in inflammation, organ failure and soft-tissue necrosis in bacterial infections. Streptococcus suis, an emerging human pathogen, can cause streptococcal toxic-shock syndrome (STSS) similarly to Streptococcus pyogenes. Currently, S. suis–platelet interactions are poorly understood. Here, we found that suilysin (SLY), the S. suis cholesterol-dependent cytolysin (CDC), was the sole stimulus of S. suis that induced platelet-neutrophil complexes (PNC) formation. Furthermore, P-selectin released in α-granules mediated PNC formation. This process was triggered by the SLY-induced pore forming-dependent Ca2+ influx. Moreover, we demonstrated that the Ca2+ influx triggered an MLCK-dependent pathway playing critical roles in P-selectin activation and PNC formation, however, PLC-β-IP3/DAG-MLCK and Rho-ROCK-MLCK signalling were not involved. Additionally, the “outside-in” signalling had a smaller effect on the SLY-induced P-selectin release and PNC formation. Interestingly, other CDCs including pneumolysin and streptolysin O have also been found to induce PNC formation in a pore forming-dependent Ca2+ influx manner. It is possible that the bacterial CDC-mediated PNC formation is a similar response mechanism used by a wide range of bacteria. These findings may provide useful insight for discovering potential therapeutic targets for S. suis-associated STSS. PMID:27830834

  2. Macroscopic domain formation in the platelet plasma membrane

    DEFF Research Database (Denmark)

    Bali, Rachna; Savino, Laura; Ramirez, Diego A.;


    There has been ample debate on whether cell membranes can present macroscopic lipid domains as predicted by three-component phase diagrams obtained by fluorescence microscopy. Several groups have argued that membrane proteins and interactions with the cytoskeleton inhibit the formation of large d...

  3. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications. (United States)

    Fortunato, Tiago M; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A; Pula, Giordano


    Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs.

  4. Formation of liquid crystalline phases in aqueous suspensions of platelet-like tripalmitin nanoparticles (United States)

    Schmiele, Martin; Gehrer, Simone; Westermann, Martin; Steiniger, Frank; Unruh, Tobias


    Suspensions of platelet-like shaped tripalmitin nanocrystals stabilized by the pure lecithin DLPC and the lecithin blend S100, respectively, have been studied by small-angle x-ray scattering (SAXS) and optical observation of their birefringence at different tripalmitin (PPP) concentrations φPPP. It could be demonstrated that the platelets of these potential drug delivery systems start to form a liquid crystalline phase already at pharmaceutically relevant concentrations φPPP of less than 10 wt. %. The details of this liquid crystalline phase are described here for the first time. As in a previous study [A. Illing et al., Pharm. Res. 21, 592 (2004)] some platelets are found to self-assemble into lamellar stacks above a critical tripalmitin concentration \\varphi _{PPP}^{st} of 4 wt. %. In this study another critical concentration \\varphi _{PPP}^{lc}≈ 7 wt. % for DLPC and \\varphi _{PPP}^{lc}≈ 9 wt. % for S100 stabilized dispersions, respectively, has been observed. \\varphi _{PPP}^{lc} describes the transition from a phase of randomly oriented stacked lamellae and remaining non-assembled individual platelets to a phase in which the stacks and non-assembled platelets exhibit an overall preferred orientation. A careful analysis of the experimental data indicates that for concentrations above \\varphi _{PPP}^{lc} the stacked lamellae start to coalesce to rather small liquid crystalline domains of nematically ordered stacks. These liquid crystalline domains can be individually very differently oriented but possess an overall preferred orientation over macroscopic length scales which becomes successively more expressed when further increasing φPPP. The lower critical concentration for the formation of liquid crystalline domains of the DLPC-stabilized suspension compared to \\varphi _{PPP}^{lc} of the S100-stabilized suspension can be explained by a larger aspect ratio of the corresponding tripalmitin platelets. A geometrical model based on the excluded volumes of

  5. Endodontic management of nonvital permanent teeth having immature roots with one step apexification, using mineral trioxide aggregate apical plug and autogenous platelet-rich fibrin membrane as an internal matrix: Case series

    Directory of Open Access Journals (Sweden)

    Vivek Sharma


    Full Text Available A tooth with blunderbuss canal and open apex can be an endodontic challenge because of difficulty in obtaining an apical seal, and existing thin radicular walls which are susceptible to fracture. To overcome the limitations of traditional long-term calcium hydroxide apexification procedures, nonsurgical one step apexification using an array of materials such as mineral trioxide aggregate (MTA has been suggested. However, adequate compaction of MTA in teeth with wide open apices can be an arduous task, and an internal matrix is required for controlled placement of MTA against which obturating material can be condensed. Platelet-rich fibrin (PRF, a second generation platelet concentrate containing several growth factors that promotes hard and soft-tissue healing, has been used as an internal matrix to create an apical plug of MTA and hence prevent extrusion of filling materials. This case series presents the endodontic management of immature permanent teeth with open apices using internal matrix of autologous PRF membrane and one step apical barrier placement of MTA.

  6. Iliac artery mural thrombus formation. Effect of antiplatelet therapy on 111In-platelet deposition in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, S.R.; Paxton, L.D.; Harker, L.A.


    To measure the rate, extent, and time course of arterial mural thrombus formation in vivo and to assess the effects of antiplatelet therapy in that setting, we have studied autologous /sup 111/In-platelet deposition induced by experimental iliac artery aneurysms in baboons. Scintillation camera imaging analyses were performed at 1, 24, 48, and 72 hours after implantation of the device. Correction for tissue attenuation was determined by using a small, comparably located /sup 111/In source implanted at the time of surgery. In five animals, /sup 111/In-platelet activity accumulated progressively after device implantation, reaching a maximum after the third day. Repeat image analysis carried out 2 weeks after the surgical procedure also showed progressive accumulation of /sup 111/In-platelets over 3 days but at markedly reduced amounts as compared with the initial study. In five additional animals, treatment with a combination of aspirin and dipyridamole begun 1 hour after surgical implantation reduced /sup 111/In-platelet deposition to negligible levels by the third day. Although platelet survival time was shortened and platelet turnover was reciprocally increased in all operated animals, platelet survival and turnover were not affected by antiplatelet therapy. We conclude that, in contrast to platelet survival and turnover measurements, /sup 111/In-platelet imaging is a reliable and sensitive method for localizing and quantifying focal arterial thrombi and for assessing the effects of antiplatelet therapy.

  7. Plugging mud

    Energy Technology Data Exchange (ETDEWEB)

    Rogoza, Z.I.; Bulla, Yu.A.; Fedorov, V.V.; Isakova, Ye.F.


    A plugging mud is proposed which includes cement, water and hydrolyzed polyacronitrile. In order to reduce water output, it additionally contains iron sulfate and sodium sulfate with the following ratio of components, % by mass: cement 68.665.42; hydrolyzed polyacronitrile 0.07-0.21; iron sulfate 0.03-0.07; sodium sulfate 0.34-1.40; water--the rest.

  8. Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation. (United States)

    Rigg, Rachel A; Healy, Laura D; Nowak, Marie S; Mallet, Jérémy; Thierheimer, Marisa L D; Pang, Jiaqing; McCarty, Owen J T; Aslan, Joseph E


    Molecular chaperones that support protein quality control, including heat shock protein 70 (Hsp70), participate in diverse aspects of cellular and physiological function. Recent studies have reported roles for specific chaperone activities in blood platelets in maintaining hemostasis; however, the functions of Hsp70 in platelet physiology remain uninvestigated. Here we characterize roles for Hsp70 activity in platelet activation and function. In vitro biochemical, microscopy, flow cytometry, and aggregometry assays of platelet function, as well as ex vivo analyses of platelet aggregate formation in whole blood under shear, were carried out under Hsp70-inhibited conditions. Inhibition of platelet Hsp70 blocked platelet aggregation and granule secretion in response to collagen-related peptide (CRP), which engages the immunoreceptor tyrosine-based activation motif-bearing collagen receptor glycoprotein VI (GPVI)-Fc receptor-γ chain complex. Hsp70 inhibition also reduced platelet integrin-αIIbβ3 activation downstream of GPVI, as Hsp70-inhibited platelets showed reduced PAC-1 and fibrinogen binding. Ex vivo, pharmacological inhibition of Hsp70 in human whole blood prevented the formation of platelet aggregates on collagen under shear. Biochemical studies supported a role for Hsp70 in maintaining the assembly of the linker for activation of T cells signalosome, which couples GPVI-initiated signaling to integrin activation, secretion, and platelet function. Together, our results suggest that Hsp70 regulates platelet activation and function by supporting linker for activation of T cells-associated signaling events downstream of platelet GPVI engagement, suggesting a role for Hsp70 in the intracellular organization of signaling systems that mediate platelet secretion, "inside-out" activation of platelet integrin-αIIbβ3, platelet-platelet aggregation, and, ultimately, hemostatic plug and thrombus formation.

  9. Increased platelet count and leucocyte-platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis.

    LENUS (Irish Health Repository)

    McCabe, D J H


    The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference.

  10. Extracellular Fibrinogen-binding Protein (Efb) from Staphylococcus aureus Inhibits the Formation of Platelet-Leukocyte Complexes. (United States)

    Posner, Mareike G; Upadhyay, Abhishek; Abubaker, Aisha Alsheikh; Fortunato, Tiago M; Vara, Dina; Canobbio, Ilaria; Bagby, Stefan; Pula, Giordano


    Extracellular fibrinogen-binding protein (Efb) from Staphylococcus aureus inhibits platelet activation, although its mechanism of action has not been established. In this study, we discovered that the N-terminal region of Efb (Efb-N) promotes platelet binding of fibrinogen and that Efb-N binding to platelets proceeds via two independent mechanisms: fibrinogen-mediated and fibrinogen-independent. By proteomic analysis of Efb-interacting proteins within platelets and confirmation by pulldown assays followed by immunoblotting, we identified P-selectin and multimerin-1 as novel Efb interaction partners. The interaction of both P-selectin and multimerin-1 with Efb is independent of fibrinogen. We focused on Efb interaction with P-selectin. Excess of P-selectin extracellular domain significantly impaired Efb binding by activated platelets, suggesting that P-selectin is the main receptor for Efb on the surface of activated platelets. Efb-N interaction with P-selectin inhibited P-selectin binding to its physiological ligand, P-selectin glycoprotein ligand-1 (PSGL-1), both in cell lysates and in cell-free assays. Because of the importance of P-selectin-PSGL-1 binding in the interaction between platelets and leukocytes, we tested human whole blood and found that Efb abolishes the formation of platelet-monocyte and platelet-granulocyte complexes. In summary, we present evidence that in addition to its documented antithrombotic activity, Efb can play an immunoregulatory role via inhibition of P-selectin-PSGL-1-dependent formation of platelet-leukocyte complexes.

  11. The role of platelets in hemostasis and the effects of snake venom toxins on platelet function. (United States)

    de Queiroz, Mayara Ribeiro; de Sousa, Bruna Barbosa; da Cunha Pereira, Déborah Fernanda; Mamede, Carla Cristine Neves; Matias, Mariana Santos; de Morais, Nadia Cristina Gomes; de Oliveira Costa, Júnia; de Oliveira, Fábio


    The human body has a set of physiological processes, known as hemostasis, which keeps the blood fluid and free of clots in normal vessels; in the case of vascular injury, this process induces the local formation of a hemostatic plug, preventing hemorrhage. The hemostatic system in humans presents complex physiological interactions that involve platelets, plasma proteins, endothelial and subendothelial structures. Disequilibrium in the regulatory mechanisms that control the growth and the size of the thrombus is one of the factors that favors the development of diseases related to vascular disorders such as myocardial infarction and stroke, which are among the leading causes of death in the western world. Interfering with platelet function is a strategy for the treatment of thrombotic diseases. Antiplatelet drugs are used mainly in cases related to arterial thrombosis and interfere in the formation of the platelet plug by different mechanisms. Aspirin (acetylsalicylic acid) is the oldest and most widely used antithrombotic drug. Although highly effective in most cases, aspirin has limitations compared to other drugs used in the treatment of homeostatic disorders. For this reason, research related to molecules that interfere with platelet aggregation are of great relevance. In this regard, snake venoms are known to contain a number of molecules that interfere with hemostasis, including platelet function. The mechanisms by which snake venom components inhibit or activate platelet aggregation are varied and can be used as tools for the diagnosis and the treatment of several hemostatic disorders. The aim of this review is to present the role of platelets in hemostasis and the mechanisms by which snake venom toxins interfere with platelet function. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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. 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.

  13. Roles of Mac-1 and glycoprotein IIb/IIIa integrins in leukocyte-platelet aggregate formation: stabilization by Mac-1 and inhibition by GpIIb/IIIa blockers. (United States)

    Patko, Zsofia; Csaszar, Albert; Acsady, Gyorgy; Peter, Karlheinz; Schwarz, Meike


    Circulating platelet-leukocyte hetero-aggregates play an important role in acute cardiovascular events and hypersensitivity reactions. The association involves the receptor families of selectins and integrin. The objective of this study was to investigate the role of CD11b/CD18 integrin (Mac-1) in hetero-aggregate formation and search for a counter-receptor on platelets ready to interact with Mac-1. As a model of leukocytes, Mac-1 presenting Chinese hamster ovary (CHO) cells were used to evaluate the role of Mac-1 in hetero-aggregate formation. The amount of CHO cell-bound active and inactive platelets was measured by flow cytometry, while the counter-receptors on platelets were identified via using blocking antibodies. We observed significant platelet adhesion on Mac-1-bearing cells when platelet-rich plasma or activated platelets were present. Inactive platelets did not adhere to Mac-1-bearing cells. Addition of fibrinogen, a ligand of Mac-1 significantly increased platelet binding. CD40L was demonstrated to act similarly on Mac-1. Inhibition of platelet GpIIb/IIIa completely abolished CHO cell-platelet aggregation. In our study, we have shown for the first time that Mac-1 mediates the formation of hetero-aggregates without selectin tethering when Mac-1 ligands such as fibrinogen or CD40L are present and blockers of platelet GpIIb/IIIa are able to diminish this interaction.

  14. Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice

    Directory of Open Access Journals (Sweden)

    Susann Rahmig


    Full Text Available Human erythro-megakaryopoiesis does not occur in humanized mouse models, preventing the in vivo analysis of human hematopoietic stem cell (HSC differentiation into these lineages in a surrogate host. Here we show that stably engrafted KIT-deficient NOD/SCID Il2rg−/− KitW41/W41 (NSGW41 mice support much improved human erythropoiesis and platelet formation compared with irradiated NSG recipients. Considerable numbers of human erythroblasts and mature thrombocytes are present in the bone marrow and blood, respectively. Morphology, composition, and enucleation capacity of de novo generated human erythroblasts in NSGW41 mice are comparable with those in human bone marrow. Overexpression of human erythropoietin showed no further improvement in human erythrocyte output, but depletion of macrophages led to the appearance of human erythrocytes in the blood. Human erythropoiesis up to normoblasts and platelet formation is fully supported in NSGW41 mice, allowing the analysis of human HSC differentiation into these lineages, the exploration of certain pathophysiologies, and the evaluation of gene therapeutic approaches.

  15. Tripeptide SQL Inhibits Platelet Aggregation and Thrombus Formation by Affecting PI3K/Akt Signaling. (United States)

    Su, Xing-li; Su, Wen; He, Zhi-long; Ming, Xin; Kong, Yi


    Centipede has been prescribed for the treatment of cardiovascular diseases in Asian countries for several hundred years. Previously, a new antiplatelet tripeptide SQL (H-Ser-Gln-Leu-OH) was isolated and characterized from centipede. In this study, we investigated its antithrombotic activities in vivo and underlying mechanism. It was found that SQL inhibited platelet aggregation induced by adenosine diphosphate, thrombin, epinephrine, and collagen and attenuated thrombus formation in both the ferric chloride-induced arterial thrombosis model and arteriovenous shunt thrombosis model in rats. It did not prolong the bleeding time in mice even at the dose of 10 mg/kg that showed potent antithrombosis effects. Molecular docking revealed that SQL binds PI3Kβ with the binding free energy of -24.341 kcal/mol, which is close to that of cocrystallized ligand (-24.220 kcal/mol). Additionally, SQL displayed inhibition on the late (180 seconds) but did not influence the early (60 seconds) Akt Ser473 phosphorylation in the immunoblot assay. These results suggest that SQL inhibits thrombus formation in vivo and that SQL inhibits PI3K-mediated signaling or even the PI3K itself in platelets. This study may help elucidate the mechanism for centipede treating cardiovascular diseases.

  16. Analysis of aggregation of platelets in thrombosis (United States)

    Ahuja, Suresh

    Platelets are key players in thrombus formation by first rolling over collagen bound von Willebrand factor followed by formation of a stable interaction with collagen. The first adhered platelets bind additional platelets until the whole injury is sealed off by a platelet aggregate. The coagulation system stabilizes the formed platelet plug by creating a tight fibrin network, and then wound contraction takes place because of morphological changes in platelets. Coagulation takes place by platelet activation and aggregation mainly through fibrinogen polymerization into fibrin fibers. The process includes multiple factors, such as thrombin, plasmin, and local shear-rate which regulate and control the process. Coagulation can be divided into two pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is initiated by the exposure of a negatively charged. It is able to activate factor XII, using a complex reaction that includes prekallikrein and high-molecular-weight kininogen as cofactors.. Thrombin is the final enzyme that is needed to convert fibrinogen into fibrin. The extrinsic pathway starts with the exposure of tissue factor to the circulating blood, which is the major initiator of coagulation. There are several feedback loops that reinforce the coagulation cascade, resulting in large amounts of thrombin. It is dependent on the presence of pro-coagulant surfaces of cells expressing negatively charged phospholipids--which include phosphatidylserine (PS)--on their outer membrane. PS-bearing surfaces are able to increase the efficiency of the reactions by concentrating and co-localizing coagulation factors.. Aggregation of platelets are analyzed and compared to adhesion of platelet to erythrocyte and to endothelial cells. This abstract is replacing MAR16-2015-020003.

  17. Orthotopic bone formation in titanium fiber mesh loaded with platelet-rich plasma and placed in segmental defects.

    NARCIS (Netherlands)

    Kroese-Deutman, H.C.; Vehof, J.W.M.; Spauwen, P.H.M.; Stoelinga, P.J.W.; Jansen, Jarno


    The effect of platelet-rich plasma (PRP) on bone formation was investigated in a rabbit segmental radial defect model. The purpose of the study was to evaluate the bone inductive properties of PRP with titanium fiber mesh and autologous bone chips in a 15-mm rabbit radial defect model. Eighteen New

  18. [Experimental research on the effects of different activators on the formation of platelet-rich gel and the release of bioactive substances in human platelet-rich plasma]. (United States)

    Yang, Y; Zhang, W; Cheng, B


    Objective: To explore the effects of calcium gluconate and thrombin on the formation of platelet-rich gel (PRG) and the release of bioactive substances in human platelet-rich plasma (PRP) and the clinical significance. Methods: Six healthy blood donors who met the inclusion criteria were recruited in our unit from May to August in 2016. Platelet samples of each donor were collected for preparation of PRP. (1) PRP in the volume of 10 mL was collected from each donor and divided into thrombin activation group (TA, added with 0.5 mL thrombin solution in dose of 100 U/mL) and calcium gluconate activation group (CGA, added with 0.5 mL calcium gluconate solution in dose of 100 g/L) according to the random number table, with 5 mL PRP in each group. Then the PRP of the two groups was activated in water bath at 37 ℃ for 1 h. The formation time of PRG was recorded, and the formation situation of PRG was observed within 1 hour of activation. After being activated for 1 h, one part of PRG was collected to observe the distribution of fibrous protein with HE staining, and another part of PRG was collected to observe platelet ultrastructure under transmission electron microscope (TEM). After being activated for 1 h, the supernatant was collected to determine the content of transforming growth factor β(1, )platelet-derived growth factor BB (PDGF-BB), vascular endothelial growth factor, basic fibroblast growth factor (bFGF), epidermal growth factor, and insulin-like growth factorⅠby enzyme-linked immunosorbent assay. (2) Another 10 mL PRP from each donor was collected and grouped as above, and the platelet suspension was obtained after two times of centrifugation and resuspension with phosphate buffered saline, respectively. And then they were treated with corresponding activator for 1 h as that in experiment (1). Nanoparticle tracking analyzer was used to detect the concentrations of microvesicles with different diameters and total microvesicles derived from platelet. Data

  19. Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis. (United States)

    Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik


    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis.

  20. Platelets can neutralize hydrogen peroxide in an acute toxicity model with cells involved in granulation tissue formation. (United States)

    Kandler, Barbara; Maitz, Philipp; Fischer, Michael B; Watzek, Georg; Gruber, Reinhard


    Platelets play a key role in the replacement of the blood clot with granulation tissue during the early steps of bone regeneration. We hypothesized that activated platelets can neutralize locally produced reactive oxygen species, thereby protecting cells involved in granulation tissue formation. The potential of platelet-released supernatant (PRS) to neutralize hydrogen peroxide (H(2)O(2)) was tested in an acute toxicity model with osteogenic, inflammatory, and endothelial cells. In the human fetal osteoblastic cell line 1.19 (hFOB), considerable morphological changes, cell shedding, and dysfunction of the respiratory chain were observed when cells were exposed to 3 mM H(2)O(2). Caspase-3 and poly-(ADP-ribose)-polymerase were not activated, suggesting that cell death occurred by necrosis. Preincubation of osteogenic cells, leukocytes, or endothelial cells with PRS decreased the acute toxicity of H(2)O(2). The capacity of platelets to release H(2)O(2)-detoxifying activity was retained for up to 72 h. Aminotriazole, an inhibitor of catalase, decreased the cytoprotective activity of PRS, whereas blocking of glutathione peroxidase by mercaptosuccinate had no effect. These results suggest that platelet-released catalase can rapidly neutralize cytotoxic amounts of H(2)O(2), a process that may play a role during the early stages of bone regeneration.

  1. Snake venom proteins and platelet thrombus formation%蛇毒蛋白与血小板血栓形成

    Institute of Scientific and Technical Information of China (English)

    李灵欣; 刘欣; 宁淑香; 李庆伟; 王继红


    多种蛇毒蛋白具有与血小板表面整合素、膜糖蛋白I b(GP I b)或血管性血友病因子(VWF)相互作用而影响血栓形成的功能.影响血小板血栓形成的蛇毒蛋白目前分为3类:去整合素、VWF调节蛇毒蛋白及GPI b结合蛋白.其中,去整合素具有高效抑制血小板聚集的功能;VWF调节蛇毒蛋白具有体外介导VWF依赖型血小板聚集的功能;而GPI b结合蛇毒蛋白又分为2组:GPI b激动剂和GPI b拮抗剂,分别起诱导血小板聚集与抑制VWF介导的血小板聚集的功能.本文将对上述影响血小板血栓形成的蛇毒蛋白的结构、功能及其在临床上的研究与应用进行综述.%Various snake venom proteins interact with platelet surface integrins, membrane glycoprotein GP I b or von Willebrand factor (VWF) to affect thrombus formation. These snake venom proteins affecting platelet thrombus formation have been classified as: disintegrins, VWF-modulating venom proteins and GP I b-binding proteins. Among them, disintegrins are strong inhibitors of platelet aggregation. VWF-modulating venom proteins can induce VWF-dependent platelet aggregation in vitro, and GP I b-binding proteins include GP I b-agonists and GP I b-antagonists, which can induce platelet aggregation and inhibit VWF-in-duced platelet aggregation, respectively. This review will focus on the structure and function of snake venom proteins that affect platelet thrombus formation in order to find value of which in sub-diagnosis of platelet disorder or von Willebrand disease, as well as for clinical and basic research of thrombosis and hemostasis.

  2. Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation.

    Directory of Open Access Journals (Sweden)

    Naadiya Carrim

    Full Text Available We have previously shown the presence of a TRAF4/p47phox/Hic5/Pyk2 complex associated with the platelet collagen receptor, GPVI, consistent with a potential role of this complex in GPVI-dependent ROS formation. In other cell systems, NOX-dependent ROS formation is facilitated by Pyk2, which along with its closely related homologue FAK are known to be activated and phosphorylated downstream of ligand binding to GPVI.To evaluate the relative roles of Pyk2 and FAK in GPVI-dependent ROS formation and to determine their location within the GPVI signaling pathway.Human and mouse washed platelets (from WT or Pyk2 KO mice were pre-treated with pharmacological inhibitors targeting FAK or Pyk2 (PF-228 and Tyrphostin A9, respectively and stimulated with the GPVI-specific agonist, CRP. FAK, but not Pyk2, was found to be essential for GPVI-dependent ROS production and aggregation. Subsequent human platelet studies with PF-228 confirmed FAK is essential for GPVI-mediated phosphatidylserine exposure, α-granule secretion (P-selectin (CD62P surface expression and integrin αIIbβ3 activation. To determine the precise location of FAK within the GPVI pathway, we analyzed the effect of PF-228 inhibition in CRP-stimulated platelets in conjunction with immunoprecipitation and pulldown analysis to show that FAK is downstream of Lyn, Spleen tyrosine kinase (Syk, PI3-K and Bruton's tyrosine kinase (Btk and upstream of Rac1, PLCγ2, Ca2+ release, PKC, Hic-5, NOX1 and αIIbβ3 activation.Overall, these data suggest a novel role for FAK in GPVI-dependent ROS formation and platelet activation and elucidate a proximal signaling role for FAK within the GPVI pathway.

  3. Effects of calcium-modified titanium implant surfaces on platelet activation, clot formation, and osseointegration. (United States)

    Anitua, Eduardo; Prado, Roberto; Orive, Gorka; Tejero, Ricardo


    The clinical success of load bearing dental and orthopedic implants relies on adequate osseointegration. Because of its favorable properties, titanium is generally considered as the material of choice. Following implant placement, titanium surfaces establish an ionic equilibrium with the surrounding tissues in which calcium plays major roles. Calcium is a cofactor of the coagulation cascade that mediates plasma protein adsorption and intervenes in a number of other intra and extracellular processes relevant for bone regeneration. In this study, titanium surfaces were modified with calcium ions (Ca(2+) surfaces) and their responses to in vitro and in vivo models were analyzed. Unlike unmodified surfaces, Ca(2+) surfaces were superhydrophilic and induced surface clot formation, platelet adsorption and activation when exposed to blood plasma. Interestingly, in vivo osseointegration using a peri-implant gap model in rabbit demonstrated that Ca(2+) surfaces significantly improved peri-implant bone volume and density at 2 weeks and bone implant contact at 8 weeks as compared to the unmodified controls. The combination of Ca(2+) surfaces with plasma rich in growth factors produced significantly more bone contact already at 2 weeks of implantation. These findings suggest the importance of the provisional matrix formation on tissue integration and highlight the clinical potential of Ca(2+) titanium surfaces as efficient stimulators of implant osseointegration.

  4. Formation of nematic liquid crystals of sterically stabilized layered double hydroxide platelets

    NARCIS (Netherlands)

    Mourad, M.C.D.; Devid, E.J.; van Schooneveld, M.M.; Vonk, Ch.; Lekkerkerker, H.N.W.


    Colloidal platelets of hydrotalcite, a layered double hydroxide, have been prepared by coprecipitation at pH 11−12 of magnesium nitrate and aluminum nitrate at two different magnesium to aluminum ratios. Changing the temperature and ionic strength during hydrothermal treatment, the platelets were ta

  5. Role of newly formed platelets in thrombus formation in rat after clopidogrel treatment

    DEFF Research Database (Denmark)

    Kuijpers, Marijke J E; Megens, Remco T A; Nikookhesal, Elham


    Platelet P2Y₁₂ receptors play an important role in arterial thrombosis by stimulating thrombus growth. Both irreversibly (clopidogrel) and reversibly binding (ticagrelor, AZD6140) P2Y₁₂ antagonists are clinically used for restricted periods, but possible differences in platelet function recovery...... after drug cessation have not been investigated. We treated WKY rats with a single, high dose of 200 mg/kg clopidogrel or 40 mg/kg ticagrelor. Blood was collected at different time points after treatment. Flow cytometry confirmed full platelet protection against ADP-induced αIIbβ₃ activation shortly...... after clopidogrel or ticagrelor treatment. At later time points after clopidogrel treatment, a subpopulation of juvenile platelets appeared that was fully responsive to ADP. Addition of ticagrelor to clopidogrel-treated blood reduced αIIbβ₃ activation of the unprotected platelets. In contrast, at later...


    MARTINI, Rosiéli; HÖRNER, Rosmari; RAMPELOTTO, Roberta Filipini; GARZON, Litiérri Razia Litiérri; NUNES, Melise Silveira; TEIXEIRA, Mayza Dalcin; GRAICHEN, Daniel Ângelo Sganzerla


    Platelet Concentrates (PCs) are the blood components with the highest rate of bacterial contamination, and coagulase-negative staphylococci (CoNS) are the most frequently isolated contaminants. This study investigated the biofilm formation of 16 contaminated units out of 691 PCs tested by phenotypic and genotypic methods. Adhesion in Borosilicate Tube (ABT) and Congo Red Agar (CRA) tests were used to assess the presence of biofilm. The presence of icaADC genes was assessed by means of the Polymerase Chain Reaction (PCR) technique. With Vitek(r)2, Staphylococcus haemolyticus was considered the most prevalent CoNS (31.25%). The CRA characterized 43.8% as probable biofilm producers, and for the ABT test, 37.5%. The icaADC genes were identified in seven samples by the PCR. The ABT technique showed 85.7% sensitivity and 100% specificity when compared to the reference method (PCR), and presented strong agreement (k = 0.8). This study shows that species identified as PCs contaminants are considered inhabitants of the normal skin flora and they might become important pathogens. The results also lead to the recommendation of ABT use in laboratory routine for detecting biofilm in CoNS contaminants of PCs. PMID:26910444

  7. The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling (United States)

    Su, Xing-li; Su, Wen; Wang, Ying; Wang, Yue-hu; Ming, Xin; Kong, Yi


    Aim: Psm2, one of the pyrrolidinoindoline alkaloids isolated from whole Selaginella moellendorffii plants, has shown a potent antiplatelet activity. In this study, we further evaluated the antiplatelet effects of Psm2, and elucidated the underlying mechanisms. Methods: Human platelet aggregation in vitro and rat platelet aggregation ex vivo were investigated. Agonist-induced platelet aggregation was measured using a light transmission aggregometer. The antithrombotic effects of Psm2 were evaluated in arteriovenous shunt thrombosis model in rats. To elucidate the mechanisms underlying the antiplatelet activity of Psm2, ELISAs, Western blotting and molecular docking were performed. The bleeding risk of Psm2 administration was assessed in a mouse tail cutting model, and the cytotoxicity of Psm2 was measured with MTT assay in EA.hy926 cells. Results: Psm2 dose-dependently inhibited human platelet aggregation induced by ADP, U4619, thrombin and collagen with IC50 values of 0.64, 0.37, 0.35 and 0.87 mg/mL, respectively. Psm2 (1, 3, 10 mg/kg) administered to rats significantly inhibited platelet aggregation ex vivo induced by ADP. Psm2 (1, 3, 10 mg/mL, iv) administered to rats with the A–V shunt dose-dependently decreased the thrombus formation. Psm2 inhibited platelet adhesion to fibrinogen and collagen with IC50 values of 84.5 and 96.5 mg/mL, respectively, but did not affect the binding of fibrinogen to GPIIb/IIIa. Furthermore, Psm2 inhibited AktSer473 phosphorylation, but did not affect MAPK signaling and Src kinase activation. Molecular docking showed that Psm2 bound to phosphatidylinositol 3-kinase β (PI3Kβ) with a binding free energy of −13.265 kcal/mol. In addition, Psm2 did not cause toxicity in EA.hy926 cells and produced only slight bleeding in a mouse tail cutting model. Conclusion: Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling. Psm2 may be a lead compound or drug candidate that could be developed for the

  8. Schisandra chinensis and Morus alba Synergistically Inhibit In Vivo Thrombus Formation and Platelet Aggregation by Impairing the Glycoprotein VI Pathway

    Directory of Open Access Journals (Sweden)

    Dong-Seon Kim


    Full Text Available Morus alba L. (MAL extract has been used in traditional medicine for its cardioprotective and antiplatelet effects, while another herbal remedy, Schisandra chinensis (SCC, has been reported to have anti-inflammatory and antioxidant properties. We evaluated underlying cellular changes exerted by extracts of these plants on platelet function and effects of SCC + MAL on in vivo thrombus formation using AV shunt and tail thrombosis-length models in rats. In vitro platelet aggregation, granule secretion, and Ca2+i release assays were carried out. The activation of integrin αIIbβ3 and phosphorylation of downstream signaling molecules, including MAPK and Akt, were investigated using cytometry and immunoblotting, respectively. Scanning electron microscopy (SEM was used to evaluate changes in platelet shape and HPLC analysis was carried out to identify the marker compounds in SCC + MAL mixture. In vivo thrombus weight and average length of tail thrombosis were significantly decreased by SCC + MAL. In vitro platelet aggregation, granule secretion, Ca2+i release, and integrin αIIbβ3 activation were notably inhibited. SCC + MAL markedly reduced the phosphorylation of MAPK pathway factors along with Akt. HPLC analysis identified four marker compounds: isoquercitrin, astragalin, schizandrol A, and gomisin A. The extracts exerted remarkable synergistic effects as natural antithrombotic and antiplatelet agent and a potent drug candidate for treating cardiovascular diseases.

  9. Skepinone-L, a Novel Potent and Highly Selective Inhibitor of p38 MAP Kinase, Effectively Impairs Platelet Activation and Thrombus Formation

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    Oliver Borst


    Full Text Available Background/Aims: Platelets are critically important for primary haemostasis and the major players in thrombotic vascular occlusion. Platelets are activated by agonists, such as thrombin and collagen-related peptide as well as second-wave mediators including thromboxane A2 via different intracellular signaling pathways resulting in degranulation, aggregation and thrombus formation. Platelet activation is paralleled by phosphorylation and activation of p38 MAPK. The limited specificity of hitherto known p38 MAPK inhibitors precluded safe conclusions on the precise role of p38 MAPK in the regulation of platelet function. The present study examined the impact of Skepinone-L, a novel and highly selective inhibitor of p38 mitogen-activated protein kinase (p38 MAPK, on platelet activation and thrombus formation. Methods: Experiments were performed in freshly isolated human platelets. Protein phosphorylation was quantified by Western blotting, thromboxane B2 synthesis by enzyme immunoassay, ATP release by ChronoLume luciferin assay, cytosolic Ca2+ concentration by Fura-2 fluorescence-measurements, platelet aggregation by a light transmissions measurement and in vitro thrombus formation by a flow chamber. Results: Skepinone-L (1 μM virtually abrogated the phosphorylation of platelet p38 MAPK substrate Hsp27 following stimulation with CRP (1 μg/ml, thrombin (5 mU/ml or thromboxane A2 analogue U-46619 (1 μM. Furthermore, Skepinone-L significantly blunted activation-dependent platelet secretion and aggregation following threshold concentrations of CRP, thrombin and thromboxane A2 analogue U-46619. Skepinone-L did not impair platelet Ca2+ signaling but prevented agonist-induced thromboxane A2 synthesis through abrogation of p38 MAPK-dependent phosphorylation of platelet cytosolic phospholipase A2 (cPLA2. Skepinone-L further markedly blunted thrombus formation under low (500-s and high (1700-s arterial shear rates. Conclusions: The present study discloses

  10. Novel anti-bacterial activities of β-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation.

    Directory of Open Access Journals (Sweden)

    Bjoern F Kraemer


    Full Text Available Human β-defensins (hBD are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus, forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET formation by target polymorphonuclear leukocytes (PMNs, which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria.

  11. Alkali treatment of microrough titanium surfaces affects macrophage/monocyte adhesion, platelet activation and architecture of blood clot formation

    Directory of Open Access Journals (Sweden)

    V Milleret


    Full Text Available Titanium implants are most commonly used for bone augmentation and replacement due to their favorable osseointegration properties. Here, hyperhydrophilic sand-blasted and acid-etched (SBA titanium surfaces were produced by alkali treatment and their responses to partially heparinized whole human blood were analyzed. Blood clot formation, platelet activation and activation of the complement system was analyzed revealing that exposure time between blood and the material surface is crucial as increasing exposure time results in higher amount of activated platelets, more blood clots formed and stronger complement activation. In contrast, the number of macrophages/monocytes found on alkali-treated surfaces was significantly reduced as compared to untreated SBA Ti surfaces. Interestingly, when comparing untreated to modified SBA Ti surfaces very different blood clots formed on their surfaces. On untreated Ti surfaces blood clots remain thin (below 15 mm, patchy and non-structured lacking large fibrin fiber networks whereas blood clots on differentiated surfaces assemble in an organized and layered architecture of more than 30 mm thickness. Close to the material surface most nucleated cells adhere, above large amounts of non-nucleated platelets remain entrapped within a dense fibrin fiber network providing a continuous cover of the entire surface. These findings might indicate that, combined with findings of previous in vivo studies demonstrating that alkali-treated SBA Ti surfaces perform better in terms of osseointegration, a continuous and structured layer of blood components on the blood-facing surface supports later tissue integration of an endosseous implant.

  12. Platelet-Derived Growth Factor B-Chain of Hematopoietic Origin Is Not Necessary for Granulation Tissue Formation and Its Absence Enhances Vascularization


    Buetow, Bernard S; Crosby, Jeffrey R.; Wolfgang E Kaminski; Ramachandran, Ravi K.; Lindahl, Per; Martin, Paul; Betsholtz, Christer; Seifert, Ronald A.; Raines, Elaine W.; Bowen-Pope, Daniel F.


    The hypothesis that wound repair is augmented by delivery of platelet-derived growth factor (PDGF) from platelets and macrophages is an attractive extrapolation from the known activities of PDGF in cell culture and in vivo. To test this hypothesis in mice, we prepared hematopoietic chimeras, in which the hematopoietic system of a normal adult mouse was replaced by the hematopoietic system of a PDGF B-chain −/− or +/+ donor. We initiated local granulation tissue formation either by implanting ...

  13. Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase. (United States)

    Zhi, Huiying; Dai, Jing; Liu, Junling; Zhu, Jieqing; Newman, Debra K; Gao, Cunji; Newman, Peter J


    IgG immune complexes contribute to the etiology and pathogenesis of numerous autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus erythematosus, rheumatoid- and collagen-induced arthritis, and chronic glomerulonephritis. Patients suffering from immune complex-related disorders are known to be susceptible to platelet-mediated thrombotic events. Though the role of the Fc receptor, FcγRIIa, in initiating platelet activation is well understood, the role of the major platelet adhesion receptor, integrin αIIbβ3, in amplifying platelet activation and mediating adhesion and aggregation downstream of encountering IgG immune complexes is poorly understood. The goal of this investigation was to gain a better understanding of the relative roles of these two receptor systems in immune complex-mediated thrombotic complications. Human platelets, and mouse platelets genetically engineered to differentially express FcγRIIa and αIIbβ3, were allowed to interact with IgG-coated surfaces under both static and flow conditions, and their ability to spread and form thrombi evaluated in the presence and absence of clinically-used fibrinogen receptor antagonists. Although binding of IgG immune complexes to FcγRIIa was sufficient for platelet adhesion and initial signal transduction events, platelet spreading and thrombus formation over IgG-coated surfaces showed an absolute requirement for αIIbβ3 and its ligands. Tyrosine kinases Lyn and Syk were found to play key roles in IgG-induced platelet activation events. Taken together, our data suggest a complex functional interplay between FcγRIIa, Lyn, and αIIbβ3 in immune complex-induced platelet activation. Future studies may be warranted to determine whether patients suffering from immune complex disorders might benefit from treatment with anti-αIIbβ3-directed therapeutics.

  14. Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase.

    Directory of Open Access Journals (Sweden)

    Huiying Zhi

    Full Text Available IgG immune complexes contribute to the etiology and pathogenesis of numerous autoimmune disorders, including heparin-induced thrombocytopenia, systemic lupus erythematosus, rheumatoid- and collagen-induced arthritis, and chronic glomerulonephritis. Patients suffering from immune complex-related disorders are known to be susceptible to platelet-mediated thrombotic events. Though the role of the Fc receptor, FcγRIIa, in initiating platelet activation is well understood, the role of the major platelet adhesion receptor, integrin αIIbβ3, in amplifying platelet activation and mediating adhesion and aggregation downstream of encountering IgG immune complexes is poorly understood. The goal of this investigation was to gain a better understanding of the relative roles of these two receptor systems in immune complex-mediated thrombotic complications. Human platelets, and mouse platelets genetically engineered to differentially express FcγRIIa and αIIbβ3, were allowed to interact with IgG-coated surfaces under both static and flow conditions, and their ability to spread and form thrombi evaluated in the presence and absence of clinically-used fibrinogen receptor antagonists. Although binding of IgG immune complexes to FcγRIIa was sufficient for platelet adhesion and initial signal transduction events, platelet spreading and thrombus formation over IgG-coated surfaces showed an absolute requirement for αIIbβ3 and its ligands. Tyrosine kinases Lyn and Syk were found to play key roles in IgG-induced platelet activation events. Taken together, our data suggest a complex functional interplay between FcγRIIa, Lyn, and αIIbβ3 in immune complex-induced platelet activation. Future studies may be warranted to determine whether patients suffering from immune complex disorders might benefit from treatment with anti-αIIbβ3-directed therapeutics.

  15. Platelets and hemostasis

    Directory of Open Access Journals (Sweden)

    M. A. Panteleev


    Full Text Available Platelets are anuclear cell fragments playing important role in hemostasis, termination of bleeding after damage, as well as in pathological thrombus formation. The main action of platelets is the formation of aggregates, overlapping the injury. They obtained the ability to aggregate by the transition process called activation. Despite the relatively simple and definite function platelet structure is very difficult: they have almost a full set of organelles, including the endoplasmic reticulum, mitochondria and other entities. When activated platelets secrete various granules interact with plasma proteins and red blood cells and other tissues. Their activation is controlled by multiple receptors and complex signaling cascades. In this review platelet structure, mechanisms of its functioning in health and disease, diagnostic methods of platelet function and approaches to their correction were considered. Particular attention will be given to those areas of the science of platelets, which still lay hidden mysteries.

  16. Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack.

    LENUS (Irish Health Repository)

    McCabe, Dominick J H


    Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and\\/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P <\\/= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P <\\/= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and\\/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.

  17. Protective Mechanisms of S. lycopersicum Aqueous Fraction (Nucleosides and Flavonoids on Platelet Activation and Thrombus Formation: In Vitro, Ex Vivo and In Vivo Studies

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    Eduardo Fuentes


    Full Text Available The purpose of this research was to investigate mechanisms of antiplatelet action of bioactive principle from S. lycopersicum. Aqueous fraction had a high content of nucleosides (adenosine, guanosine, and adenosine 5′-monophosphate by HPLC analysis. Also aqueous fraction presented flavonoids content. Aqueous fraction inhibited platelet activation by 15 ± 6% (P<0.05. Fully spread of human platelets on collagen in the presence of aqueous fraction was inhibited from 15 ± 1 to 9 ± 1 μm2 (P<0.001. After incubation of whole blood with aqueous fraction, the platelet coverage was inhibited by 55 ± 12% (P<0.001. Platelet ATP secretion and aggregation were significantly inhibited by the aqueous fraction. At the same concentrations that aqueous fraction inhibits platelet aggregation, levels of sCD40L significantly decreased and the intraplatelet cAMP levels increased. In addition, SQ22536, an adenylate cyclase inhibitor, attenuated the effect of aqueous fraction toward ADP-induced platelet aggregation and intraplatelet level of cAMP. Platelet aggregation ex vivo (human study and thrombosis formation in vivo (murine model were inhibited by aqueous fraction. Finally, aqueous fraction may be used as a functional ingredient adding antiplatelet activities (nucleosides and flavonoids to processed foods.

  18. Effect of in-water oxygen prebreathing at different depths on decompression-induced bubble formation and platelet activation. (United States)

    Bosco, Gerardo; Yang, Zhong-jin; Di Tano, Guglielmo; Camporesi, Enrico M; Faralli, Fabio; Savini, Fabio; Landolfi, Angelo; Doria, Christian; Fanò, Giorgio


    Effect of in-water oxygen prebreathing at different depths on decompression-induced bubble formation and platelet activation in scuba divers was evaluated. Six volunteers participated in four diving protocols, with 2 wk of recovery between dives. On dive 1, before diving, all divers breathed normally for 20 min at the surface of the sea (Air). On dive 2, before diving, all divers breathed 100% oxygen for 20 min at the surface of the sea [normobaric oxygenation (NBO)]. On dive 3, before diving, all divers breathed 100% O2 for 20 min at 6 m of seawater [msw; hyperbaric oxygenation (HBO) 1.6 atmospheres absolute (ATA)]. On dive 4, before diving, all divers breathed 100% O2 for 20 min at 12 msw (HBO 2.2 ATA). Then they dove to 30 msw (4 ATA) for 20 min breathing air from scuba. After each dive, blood samples were collected as soon as the divers surfaced. Bubbles were measured at 20 and 50 min after decompression and converted to bubble count estimate (BCE) and numeric bubble grade (NBG). BCE and NBG were significantly lower in NBO than in Air [0.142+/-0.034 vs. 0.191+/-0.066 (Pbubbles and platelet activation and, therefore, may be beneficial in reducing the development of decompression sickness.

  19. Role of G protein signaling in the formation of the fibrin(ogen)-integrin αIIbβ3-actin cytoskeleton complex in platelets. (United States)

    Budnik, Ivan; Shenkman, Boris; Savion, Naphtali


    Effective platelet function requires formation of a physical link between fibrin(ogen), integrin αIIbβ3, and cytoplasmic actin filaments. We investigated the role of the Gαq, Gαi, and Gα12/13 families of heterotrimeric GTP-binding proteins (G proteins) in the assembly of a ligand-αIIbβ3-actin cytoskeleton complex. Selective and combined activation of the G proteins was achieved by using combinations of various platelet agonists and inhibitors. Formation and stability of fibrinogen-αIIbβ3 interaction were evaluated by the extent of platelet aggregation and the rate of eptifibatide-induced platelet disaggregation; association of αIIbβ3 with the cytoskeleton was analyzed by western blot. Formation of the fibrin-αIIbβ3-actin cytoskeleton complex was evaluated by rotational thromboelastometry assay in which clot formation was induced by the mixture of reptilase and factor XIIIa. We demonstrated that involvement of heterotrimeric G proteins in the formation of the ligand-αIIbβ3-cytoskeleton complex depends on whether fibrinogen or fibrin serves as the integrin ligand. Formation of the fibrinogen-αIIbβ3-cytoskeleton complex requires combined activation of at least two G protein pathways while the maximal αIIbβ3-cytoskeleton association and the strongest αIIbβ3-fibrinogen binding supporting irreversible platelet aggregation require combined activation of all three-Gαq, Gαi, and Gα12/13-G protein families. In contrast, formation of the fibrin-αIIbβ3-cytoskeleton complex mediating clot retraction is critically dependent on the activation of the Gαi family, especially on the activation of Gαz.

  20. Plug Load Data (United States)

    National Aeronautics and Space Administration — We provide MATLAB binary files (.mat) and comma separated values files of data collected from a pilot study of a plug load management system that allows for the...

  1. Platelet cytoskeleton and its hemostatic role. (United States)

    Cerecedo, Doris


    Upon vascular injury, platelets adhere to the exposed extracellular matrix, which triggers the platelet activation and aggregation to form a hemostatic plug to seal the wound. All of these events involve dramatic changes in shape because of the cytoskeleton reorganization. The versatility of the cytoskeleton's main elements depends on the biochemical nature of the elements, as well as on the associated proteins that confer multiple functions within the cell. The list of these associated proteins grows actively, increasing our knowledge concerning the complexity of platelet cytoskeleton machinery. The present review evidences the recently described platelet proteins that promote characteristic modifications in their cytoskeleton organization, with special focus on the dystrophin-glycoprotein complex.

  2. Incomplete left atrial appendage occlusion and thrombus formation after Watchman implantation treated with anticoagulation followed by further transcatheter closure with a second-generation Amplatzer Cardiac Plug (Amulet device). (United States)

    Lam, Simon Cheung Chi; Bertog, Stefan; Sievert, Horst


    We report a case of incomplete left atrial appendage (LAA) closure after Watchman device (Atritech, Boston Scientific, Natrick, MA) implantation which subsequently developed a thrombus 3 years after the initial procedure. The thrombus resolved after a short period of anticoagulation with warfarin, and the LAA was successfully occluded with a second-generation Amplatzer Cardiac Plug (Amulet device, AGA, St Jude Medical, Minneapolis, MN). Incomplete LAA closure may be associated with increased risk of thrombus formation and further closure with a second device after a course of anticoagulation may be a reasonable and feasible strategy. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  3. Platelet adhesion: structural and functional diversity of short dystrophin and utrophins in the formation of dystrophin-associated-protein complexes related to actin dynamics. (United States)

    Cerecedo, Doris; Martínez-Rojas, Dalila; Chávez, Oscar; Martínez-Pérez, Francisco; García-Sierra, Francisco; Rendon, Alvaro; Mornet, Dominique; Mondragón, Ricardo


    Platelets are dynamic cell fragments that modify their shape during activation. Utrophin and dystrophins are minor actin-binding proteins present in muscle and non-muscle cytoskeleton. In the present study, we characterised the pattern of Dp71 isoforms and utrophin gene products by immunoblot in human platelets. Two new dystrophin isoforms were found, Dp71f and Dp71 d, as well as the Up71 isoform and the dystrophin-associated proteins, alpha and beta -dystrobrevins. Distribution of Dp71d/Dp71delta110m, Up400/Up71 and dystrophin-associated proteins in relation to the actin cytoskeleton was evaluated by confocal microscopy in both resting and platelets adhered on glass. Formation of two dystrophin-associated protein complexes (Dp71d/Dp71delta110m approximately DAPC and Up400/Up71 approximately DAPC) was demonstrated by co-immunoprecipitation and their distribution in relation to the actin cytoskeleton was characterised during platelet adhesion. The Dp71d/Dp71delta100m approximately DAPC is maintained mainly at the granulomere and is associated with dynamic structures during activation by adhesion to thrombin-coated surfaces. Participation of both Dp71d/Dp71delta110m approximately DAPC and Up400/Up71 approximately DAPC in the biological roles of the platelets is discussed.

  4. Platelet-derived growth factor receptor beta is critical for zebrafish intersegmental vessel formation.

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    Katie M Wiens

    Full Text Available BACKGROUND: Platelet-derived growth factor receptor beta (PDGFRbeta is a tyrosine kinase receptor known to affect vascular development. The zebrafish is an excellent model to study specific regulators of vascular development, yet the role of PDGF signaling has not been determined in early zebrafish embryos. Furthermore, vascular mural cells, in which PDGFRbeta functions cell autonomously in other systems, have not been identified in zebrafish embryos younger than 72 hours post fertilization. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate the role of PDGFRbeta in zebrafish vascular development, we cloned the highly conserved zebrafish homolog of PDGFRbeta. We found that pdgfrbeta is expressed in the hypochord, a developmental structure that is immediately dorsal to the dorsal aorta and potentially regulates blood vessel development in the zebrafish. Using a PDGFR tyrosine kinase inhibitor, a morpholino oligonucleotide specific to PDGFRbeta, and a dominant negative PDGFRbeta transgenic line, we found that PDGFRbeta is necessary for angiogenesis of the intersegmental vessels. SIGNIFICANCE/CONCLUSION: Our data provide the first evidence that PDGFRbeta signaling is required for zebrafish angiogenesis. We propose a novel mechanism for zebrafish PDGFRbeta signaling that regulates vascular angiogenesis in the absence of mural cells.

  5. Platelet full length TFPI-α in healthy volunteers is not affected by sex or hormonal use (United States)

    Winckers, Kristien; Thomassen, Stella; ten Cate, Hugo; Hackeng, Tilman M.


    Background Only 10% of plasma TFPIα (TFPI) exists in the full length form, the rest circulates as a C-terminally truncated form. However, blood platelets exclusively contain full length TFPI, which is released at the site of injury upon platelet activation, and which could play an important local regulatory role in thrombin generation and prevention of thrombosis. Methods The anticoagulant activities of full length and truncated TFPI were investigated using thrombin generation assays. Blood samples were obtained from 30 healthy volunteers (10 male subjects, 10 female subjects, and 10 females using oral contraceptives). Platelet TFPI was released in platelet rich plasma and in platelet isolates using convulxin or thrombin, and measured by free TFPI ELISA and thrombin generation assays. Results Full length TFPI and platelet TFPI were much more potent inhibitors of thrombin generation than truncated TFPI, which was virtually inactive. Although mean plasma TFPI antigen levels decreased from men (0.30 nM) to women (0.20 nM) to women using oral contraceptives (0.11 nM), no relevant differences were found in platelet TFPI among those subgroups. Conclusions Platelets release similar amounts of TFPI regardless of plasma TFPI concentrations and is unaffected by sex or oral contraceptive use. We speculate that platelet TFPI is important to prevent systemic coagulation and thrombosis and restrict thrombus formation to the site of the growing platelet plug. The stable contribution of platelet TFPI to the anticoagulant potential in plasma is likely to become particularly relevant under conditions of low plasma TFPI levels in combination of oral contraceptives use. PMID:28158181

  6. Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: A Potential Impact on Early Bone Healing.

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    Xin Wang

    Full Text Available Hematoma quality (especially the fibrin matrix plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β on fibrin clot formation from platelet-poor plasma (PPP.Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG, blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10 min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM, confocal microscopy (CM, turbidity, and clot lysis assays.The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β compared to the control group without IL-1β (543.8 ± 205.8. Maximal turbidity was observed in the control group. IL-1β (500 pg/mL treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05. The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers.IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

  7. Bone marrow AT1 augments neointima formation by promoting mobilization of smooth muscle progenitors via platelet-derived SDF-1{alpha}. (United States)

    Yokoi, Hirokazu; Yamada, Hiroyuki; Tsubakimoto, Yoshinori; Takata, Hiroki; Kawahito, Hiroyuki; Kishida, Sou; Kato, Taku; Matsui, Akihiro; Hirai, Hideyo; Ashihara, Eishi; Maekawa, Taira; Iwai, Masaru; Horiuchi, Masatsugu; Ikeda, Kouji; Takahashi, Tomosaburo; Okigaki, Mitsuhiko; Matsubara, Hiroaki


    Bone marrow (BM)-derived endothelial progenitor cells (EPCs) and vascular smooth muscle progenitor cells (VPCs) contribute to neointima formation, whereas the angiotensin II (Ang II) type 1 receptor (AT(1))-mediated action on BM-derived progenitors remains undefined. A wire-induced vascular injury was performed in the femoral artery of BM-chimeric mice whose BM was repopulated with AT(1)-deficient (BM-Agtr1(-/-)) or wild-type (BM-Agtr1(+/+)) cells. Neointima formation was profoundly reduced by 38% in BM-Agtr1(-/-) mice. Although the number of circulating EPCs (Sca-1(+)Flk-1(+)) and extent of reendothelialization did not differ between the 2 groups, the numbers of both circulating VPCs (c-Kit(-)Sca-1(+)Lin(-)) and tissue VPCs (Sca-1(+)CD31(-)) incorporated into neointima were markedly decreased in BM-Agtr1(-/-) mice. The accumulation of aggregated platelets and their content of stromal cell-derived factor-1alpha (SDF-1alpha) were significantly reduced in BM-Agtr1(-/-) mice, accompanied by a decrease in the serum level of SDF-1alpha. Thrombin-induced platelets aggregation was dose-dependently inhibited (45% at 0.1 IU/mL, PAgtr1(-/-) platelets compared with Agtr1(+/+) platelets, accompanied by the reduced expression and release of SDF-1alpha. The BM-AT(1) receptor promotes neointima formation by regulating the mobilization and homing of BM-derived VPCs in a platelet-derived SDF-1alpha-dependent manner without affecting EPC-mediated reendothelialization.

  8. In situ platelets formation into aqueous polymer colloids: The topochemical transformation from single to double layered hydroxide (LSH-LDH) uncovered. (United States)

    Stimpfling, Thomas; Langry, Arthur; Hintze-Bruening, Horst; Leroux, Fabrice


    Layered Single Hydroxide (LSH) of chemical composition Zn5(OH)8(acetate)2·nH2O is synthesized under in situ condition in an aqueous dispersion of an amphiphilic, carboxylate bearing polyester via a modified polyol route. The one-pot LSH generation yields agglomerates of well intercalated platelets, 9-10nm separated from each other. However the corresponding Layered Double Hydroxide (LDH) of formal composition Zn2Al(OH)6 (acetate)·nH2O is found to proceed via the formation of crystallized, similarly spaced LSH sheets in the neighborhood of amorphous Al rich domains as evidenced by X-ray diffraction and transmission electron micrographs. The initial phase segregation effaces over time while LSH platelets convert into the LDH phase. Fingerprinted by the change of in-plane cation accommodation, the associated topochemical reaction of the edge-sharing octahedral LSH platelets involves the transformation of metal lacunae, adjacently covered by one tetrahedral coordinated cation on each side to balance the negative surcharge, into fully occupied and monolayered platelets of edge-sharing octahedral LDH, the former voids being occupied by trivalent cations. This replenishing process of empty sites, coupled with the dissolution of tetrahedral sites is likely to be observed for the first time due to the presence of well separated, polymer intercalated platelets. TEM pictures vision crystal growth arising from the zone of the LSH edge-slab and by using solid state kinetics formalism the associated high activation energy of the first-order reaction agrees well with a plausible dissolution re-precipitation mechanism. The conversion of LSH into LDH platelets may be extended to others cations as Co(2+), Cu(2+), as well as the aluminum source (AlCl3) and the water-soluble polymer (NVP), thus indicating it is a new prevalent facet of LDH.

  9. A point mutation in the EGF-4 domain of β(3) integrin is responsible for the formation of the Sec(a) platelet alloantigen and affects receptor function. (United States)

    Sachs, Ulrich J; Bakchoul, Tamam; Eva, Olga; Giptner, Astrid; Bein, Gregor; Aster, Richard H; Gitter, Maria; Peterson, Julie; Santoso, Sentot


    Neonatal alloimmune thrombocytopenia (NAIT) is caused by fetomaternal platelet incompatibility with maternal antibodies crossing the placenta and destroying fetal platelets. Antibodies against human platelet antigen-1a (HPA-1a) and HPA-5b are responsible for the majority of NAIT cases. We observed a suspected NAIT in a newborn with a platelet count of 25 G/l and petechial haemorrhages. Serological analysis of maternal serum revealed an immunisation against αIIbβ3 on paternal platelets only, indicating the presence of an antibody against a new rare alloantigen (Sec(a)) residing on αIIbβ3. The location of Sec(a) on αIIbβ3 was confirmed by immunoprecipitation. Nucleotide sequence analysis of paternal β3 revealed a single nucleotide exchange (G(1818)T) in exon 11 of the β3 gene (ITGB3), changing Lys(580) (wild-type) to Asn(580) (Sec(a)). Two additional members of the family Sec were typed Sec(a) positive, but none of 300 blood donors. Chinese hamster ovary cells expressing Asn(580), but not Lys(580) αIIbβ3, bound anti-Sec(a), which was corroborated by immunoprecipitation. Adhesion of transfected cells onto immobilised fibrinogen showed reduced binding of the Asn(580) variant compared to wild-type αIIbβ3. Analysis of transfected cells with anti-LIBS and PAC-1 antibody showed reduced binding when compared to the wild-type. No such effects were observed with Sec(a) positive platelets, which, however, are heterozygous for the Lys(580)Asn mutation. In this study, we describe a NAIT case caused by maternal alloimmunisation against a new antigen on αIIbβ3. Analysis with mutant transfected cells showed that the Lys(580)Asn mutation responsible for the formation of the Sec(a) antigenic determinant affects αIIbβ3 receptor function.

  10. The effect of an Nd-YAG pulsed laser on the cleaning of the root canal and the formation of a fused apical plug. (United States)

    Saunders, W P; Whitters, C J; Strang, R; Moseley, H; Payne, A P; McGadey, J


    A Neodymium-yttrium aluminium garnet (Nd-YAG) pulsed laser was used in vitro to determine whether various laser energy levels from 0.75 W to 1.7 W at 15 pulses s(-1) (pps) were able to (i) remove debris from the walls of prepared root canals (ii) remove pulpal tissue from unprepared canals and (iii) create a fused apical plug from dentine chips, hydroxyapatite (HAP) or low-fusing dental porcelain. Single-rooted teeth were sectioned at the amelocemental junction and the crowns discarded. The root canals of 50 teeth were prepared chemomechanically and allocated to four groups of 10 teeth for laser treatment. One group was left unlased as a control. After lasing, the teeth were split longitudinally, stained and examined for residual debris. Results showed that there was no statistically significant difference between the groups (Plaser energy was applied to dentine chips, HAP and low-fusing porcelain in an attempt to produce a fused apical plug. The laser was unable to melt the dentine chips but some hardening of HAP occurred when combined with blue food-colouring, with or without glycerine, at energy levels of 1.0 W, at 15 pps for 30 s. Superficial hardening of low-fusing porcelain occurred at 1.0 W, 15 pps for 30 s.

  11. Playing with Plug-ins (United States)

    Thompson, Douglas E.


    In today's complex music software packages, many features can remain unexplored and unused. Software plug-ins--available in most every music software package, yet easily overlooked in the software's basic operations--are one such feature. In this article, I introduce readers to plug-ins and offer tips for purchasing plug-ins I have…

  12. Vascular plugs - A key companion to Interventionists - 'Just Plug it'. (United States)

    Ramakrishnan, Sivasubramanian


    Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory.

  13. Platelet-derived growth factor B-chain of hematopoietic origin is not necessary for granulation tissue formation and its absence enhances vascularization. (United States)

    Buetow, B S; Crosby, J R; Kaminski, W E; Ramachandran, R K; Lindahl, P; Martin, P; Betsholtz, C; Seifert, R A; Raines, E W; Bowen-Pope, D F


    The hypothesis that wound repair is augmented by delivery of platelet-derived growth factor (PDGF) from platelets and macrophages is an attractive extrapolation from the known activities of PDGF in cell culture and in vivo. To test this hypothesis in mice, we prepared hematopoietic chimeras, in which the hematopoietic system of a normal adult mouse was replaced by the hematopoietic system of a PDGF B-chain -/- or +/+ donor. We initiated local granulation tissue formation either by implanting small surgical sponges to elicit a foreign body granulation tissue response, or by ligating the left common carotid to form an organized thrombus. We found that the absence of hematopoietic PDGF B-chain did not decrease the extent of granulation tissue or vascular lesion formation, and that the vascularization of both lesions increased by approximately 100%. We conclude that PDGF B-chain from cells of hematopoietic origin, including platelets and macrophages, is not important for granulation tissue formation, and that it reduces vascularization of granulation issue, probably through disabling of the short-range chemotactic gradients of PDGF that are important for recruiting pericytes/smooth muscle cells to the endothelium of new vessels.

  14. Flavanols and Platelet Reactivity

    Directory of Open Access Journals (Sweden)

    Debra A. Pearson


    Full Text Available Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular disease. An increasing number of foods have been reported to have platelet-inhibitory actions, and research with a number of flavanol-rich foods, including, grape juice, cocoa and chocolate, suggests that these foods may provide some protection against thrombosis. In the present report, we review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa inhibited several measures of platelet activity including, epinephrine- and ADP-induced glycoprotein (GP IIb/IIIa and P-Selectin expression, platelet microparticle formation, and epinephrine-collagen and ADP-collagen induced primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and primary hemostasis were similar to, though less robust than those associated with the use of low dose (81 mg aspirin. These data, coupled with information from other studies, support the concept that flavanols present in cocoa and chocolate can modulate platelet function through a multitude of pathways.

  15. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti


    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  16. Platelet mimicry

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Hunter, Alan Christy; Peer, Dan


    Here we critically examine whether coating of nanoparticles with platelet membranes can truly disguise them against recognition by elements of the innate immune system. We further assess whether the "cloaking technology" can sufficiently equip nanoparticles with platelet-mimicking functionalities...

  17. Platelet Count (United States)

    ... their spleen removed surgically Use of birth control pills (oral contraceptives) Some conditions may cause a temporary (transitory) increased ... increased platelet counts include estrogen and birth control pills (oral contraceptives). Mildly decreased platelet counts may be seen in ...

  18. Deposition of fibrinogen on the surface of in vitro thrombi prevents platelet adhesion. (United States)

    Owaynat, Hadil; Yermolenko, Ivan S; Turaga, Ramya; Lishko, Valeryi K; Sheller, Michael R; Ugarova, Tatiana P


    The initial accumulation of platelets after vessel injury is followed by thrombin-mediated generation of fibrin which is deposited around the plug. While numerous in vitro studies have shown that fibrin is highly adhesive for platelets, the surface of experimental thrombi in vivo contains very few platelets suggesting the existence of natural anti-adhesive mechanisms protecting stabilized thrombi from platelet accumulation and continuous thrombus propagation. We previously showed that adsorption of fibrinogen on pure fibrin clots results in the formation of a nonadhesive matrix, highlighting a possible role of this process in surface-mediated control of thrombus growth. However, the deposition of fibrinogen on the surface of blood clots has not been examined. In this study, we investigated the presence of intact fibrinogen on the surface of fibrin-rich thrombi generated from flowing blood and determined whether deposited fibrinogen is nonadhesive for platelets. Stabilized fibrin-rich thrombi were generated using a flow chamber and the time that platelets spend on the surface of thrombi was determined by video recording. The presence of fibrinogen and fibrin on the surface of thrombi was analyzed by confocal microscopy using specific antibodies. Examination of the spatial distribution of two proteins revealed the presence of intact fibrinogen on the surface of stabilized thrombi. By manipulating the surface of thrombi to display either fibrin or intact fibrinogen, we found that platelets adhere to fibrin- but not to fibrinogen-coated thrombi. These results indicate that the fibrinogen matrix assembled on the outer layer of stabilized in vitro thrombi protects them from platelet adhesion.

  19. The Utilization of the Microflora Indigenous to and Present in Oil-Bearing Formations to Selectively Plug the More Porous Zones Thereby Increasing Oil Recovery During Waterflooding

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Lewis R.; Stephens, James O.; Vadie, Alex A.


    The objective of this work is to demonstrate the use of indigenous microbes as a method of profile control in waterfloods. It is expected that as the microbial population is induced to increase, that the expanded biomass will selectively block the more permeable zones of the reservoir thereby forcing injection water to flow through the less permeable zones which will result in improved sweep efficiency. This increase in microbial population will be accomplished by injecting a nutrient solution into four injectors. Four other injectors will act as control wells. During Phase I, two wells will be cored through the zone of interest. The core will be subjected to special core analyses in order to arrive at the optimum nutrient formulation. During Phase II, nutrient injection will begin, the results monitored, and adjustments to the nutrient composition made, if necessary. Phase II also will include the drilling of three wells for post-mortem core analysis. Phase III will focus on technology transfer of the results. It should be pointed out that one expected outcome of this new technology will be a prolongation of economical waterflooding operations, i.e. economical oil recovery should continue for much longer periods in the producing wells subjected to this selective plugging technique.

  20. Rho GTPases in platelet function. (United States)

    Aslan, J E; McCarty, O J T


    The Rho family of GTP binding proteins, also commonly referred to as the Rho GTPases, are master regulators of the platelet cytoskeleton and platelet function. These low-molecular-weight or 'small' GTPases act as signaling switches in the spatial and temporal transduction, and amplification of signals from platelet cell surface receptors to the intracellular signaling pathways that drive platelet function. The Rho GTPase family members RhoA, Cdc42 and Rac1 have emerged as key regulators in the dynamics of the actin cytoskeleton in platelets and play key roles in platelet aggregation, secretion, spreading and thrombus formation. Rho GTPase regulators, including GEFs and GAPs and downstream effectors, such as the WASPs, formins and PAKs, may also regulate platelet activation and function. In this review, we provide an overview of Rho GTPase signaling in platelet physiology. Previous studies of Rho GTPases and platelets have had a shared history, as platelets have served as an ideal, non-transformed cellular model to characterize Rho function. Likewise, recent studies of the cell biology of Rho GTPase family members have helped to build an understanding of the molecular regulation of platelet function and will continue to do so through the further characterization of Rho GTPases as well as Rho GAPs, GEFs, RhoGDIs and Rho effectors in actin reorganization and other Rho-driven cellular processes. © 2012 International Society on Thrombosis and Haemostasis.

  1. Providing free autopoweroff plugs

    DEFF Research Database (Denmark)

    Jensen, Carsten Lynge; Hansen, Lars Gårn; Fjordbak, Troels


    on metered electricity consumption for different types of households. We find effects for single men and couples without children, while we find no effect for single women and households with children. We suggest that this could be because of differences in saving potential (e.g. some households do not have...... appliances where using a plug is relevant), differences in the skills relevant for installing the technology and differences in the willingness to spend time and effort on installation. We conclude that targeting interventions at more responsive households, and tailoring interventions to target groups, can...

  2. Device-associated thrombus formation after left atrial appendage occlusion: A systematic review of events reported with the Watchman, the Amplatzer Cardiac Plug and the Amulet. (United States)

    Lempereur, Mathieu; Aminian, Adel; Freixa, Xavier; Gafoor, Sameer; Kefer, Joelle; Tzikas, Apostolos; Legrand, Victor; Saw, Jacqueline


    This study aimed to provide a systematic review of device-associated thrombosis (DAT) after left atrial appendage occlusion (LAAO) with the Watchman, Amplatzer Cardiac Plug, and Amulet devices. DAT is known as a complication of LAAO but data about its clinical impact is scarce. A systematic review of studies evaluating the incidence, treatment and clinical implications of DAT from January 2008 to September 2015 was conducted. A total of 30 studies describing DAT events were included in the analysis. The overall incidence of DAT was 3.9% (82 DAT for 2118 implanted devices). The median time from procedure to diagnosis of DAT was 1.5 months (IQR: 0-2.9). Most cases were diagnosed with transesophageal echocardiogram (TEE). The treatment consisted of low molecular weight heparin (LMWH) in 45.5% of cases, and oral anticoagulation (OAC) or other treatment modalities in 54.5%. Complete thrombus resolution was achieved in 95.0% of cases (100% with LMWH and 89.5% with OAC). Treatment duration varied greatly with a median treatment duration of 45 days (IQR: 14-135). Clinical events related to DAT consisted of neurologic events namely two transient ischemic attacks (2.4%) and four ischemic strokes (4.9%). DAT is an infrequent complication of percutaneous LAAO. It occurs mainly early after the procedure and is associated with a low rate of neurological complications. In the majority of cases, diagnosis is made during follow-up imaging with TEE. Anticoagulation treatment seems to be safe and highly effective. Further studies are needed to evaluate the optimal management of DAT. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Silencing of the Hsf gene, the transcriptional regulator of A. gambiae male accessory glands, inhibits the formation of the mating plug in mated females and disrupts their monogamous behaviour. (United States)

    Dottorini, Tania; Persampieri, Tania; Palladino, Pietro; Spaccapelo, Roberta; Crisanti, Andrea


    Discovering the molecular factors that shape the mating behaviour and the fertility of the mosquito Anopheles gambiae, the principal vector of human malaria, is regarded as critical to better understand its reproductive success as well as for identifying new leads for malaria control measures. In A. gambiae mating induces complex behavioural and physiological changes in the females, including refractoriness to subsequent mating and induction of egg-laying. In other insects including Drosophila a group of proteins named Accessory gland proteins (Acps), produced by males and transferred with sperm to the female reproductive tract, have been implicated in this post-mating response. Although Acps represent a set of promising candidates for unravelling the mating physiology, their role in inducing behavioural changes in mated A. gambiae females remains largely unknown. In this work, we demonstrate that a down-regulation of a large fraction of Acp genes via silencing of the Acp regulating transcription factor Hsf, abolishes the formation of mating plug in mated females and fails to induce refractoriness of mated female to subsequent inseminations. A significant fraction of females mated to Hsf silenced males (66%) failed to receive the mating plug though seminal fluid had been transferred as documented by the presence of spermatozoa in the female sperm storage organ. Furthermore, nearly all females (95%) mated to HSF-silenced males were re-inseminated when exposed to males carrying EGPF marked sperm. Our findings provide evidence showing that Acp genes regulated by the transcription factor HSF play a key role in the function of the male accessory glands.


    Ponomareva, A A; Nevzorova, T A; Mordakhanova, E R; Andrianova, I A; Litvinov, R I


    Platelets are the anucleated blood cells, wich together with the fibrin stop bleeding (hemostasis). Cellular microvesicles are membrane-surrounded microparticles released into extracellular space upon activation and/or apoptosis of various cells. Platelet-derived macrovesicles from the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the pathophysiology of platelet-derived macrovesicles, mechanisms of their formation and structural details remain poorly understood. Here we investigated the ultrastructure of parental platelets and platelet-derived microvesicles formed in vitro by quiescent cells as well as by cells stimulated with one of the following activators: arachidonic acid, ADP, thrombin, calcium ionophore A23187. Using transmission electron microscopy of human platelets and isolated microvesicles, we analyzed the intracellular origin, steps of formation, structural diversity, and size distributions of the subcellular particles. We have revealed that thrombin, unlike other stimuli, not only induced vesiculation of the plasma membrane but also caused break-up of the cells followed by formation of microparticles that are comparable with microvesicles by size. A fraction of these microparticles contained cellular organelles surrounded by a thin membrane. The size of platelet-derived macrovesicles varied from 30 nm to 500 nm, however, the size distributions depended on the nature of a cell-activating stimulus. The results obtained provide new information about the formation of platelet-derived macrovesicles and their structural diversity, wich is important to understand their multiple functions in normal and disease states.

  5. Molecular interplay between platelets and the vascular wall in thrombosis and hemostasis. (United States)

    Berna-Erro, Alejandro; Redondo, Pedro C; Lopez, Esther; Albarran, Letizia; Rosado, Juan A


    Hemostasis is an intrinsic property of the vascular system that prevents blood loss during accidental disruption of the vessel wall. Late mechanisms of hemostasis comprise vessel repair and wound healing. In contrast, the early mechanism of hemostasis comprises the quick formation of a blood cell plug, also known as thrombus, whose function is to seal the region of the vessel near the compromised surface or area. Despite the simplicity of the concept, the molecular mechanisms underlying early hemostasis are highly complex. The local rheological properties of the blood flow, the vascular region and the nature of the injury determine the mechanism of thrombogenesis. Components of the plasma, blood cells such as platelets and vascular endothelial cells are involved in thrombosis. This review focuses on platelet-vascular wall interactions during thrombosis and hemostasis and provides an overview of the main underlying molecular mechanisms.

  6. Mechanics Model of Plug Welding (United States)

    Zuo, Q. K.; Nunes, A. C., Jr.


    An analytical model has been developed for the mechanics of friction plug welding. The model accounts for coupling of plastic deformation (material flow) and thermal response (plastic heating). The model predictions of the torque, energy, and pull force on the plug were compared to the data of a recent experiment, and the agreements between predictions and data are encouraging.

  7. Static Gas-Charging Plug (United States)

    Indoe, William


    A gas-charging plug can be easily analyzed for random vibration. The design features two steeped O-rings in a radial configuration at two different diameters, with a 0.050-in. (.1.3-mm) diameter through-hole between the two O-rings. In the charging state, the top O-ring is engaged and sealing. The bottom O-ring outer diameter is not squeezed, and allows air to flow by it into the tank. The inner diameter is stretched to plug the gland diameter, and is restrained by the O-ring groove. The charging port bushing provides mechanical stop to restrain the plug during gas charge removal. It also prevents the plug from becoming a projectile when removing gas charge from the accumulator. The plug can easily be verified after installation to ensure leakage requirements are met.

  8. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    Jonas S De Jong


    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  9. Platelet lipidomic. (United States)

    Dolegowska, B; Lubkowska, A; De Girolamo, L


    Lipids account for 16-19 percent dry platelet matter and includes 65 percent phospholipids, 25 percent neutral lipids and about 8 percent glycosphingolipids. The cell membrane that surrounds platelets is a bilayer that contains different types phospholipids symmetrically distributed in resting platelets, such as phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylcholine, and sphingomyelin. The collapse of lipid asymmetry is exposure of phosphatidylserine in the external leaflet of the plasma bilayer, where it is known to serve at least two major functions: providing a platform for development of the blood coagulation cascade and presenting the signal that induces phagocytosis of apoptotic cells. During activation, this asymmetrical distribution becomes disrupted, and PS and PE become exposed on the cell surface. The transbilayer movement of phosphatidylserine is responsible for the platelet procoagulant activity. Exposure of phosphatidylserine is a flag for macrophage recognition and clearance from the circulation. Platelets, stored at room temperature for transfusion for more than 5 days, undergo changes collectively known as platelet storage lesions. Thus, the platelet lipid composition and its possible modifications over time are crucial for efficacy of platelet rich plasma therapy. Moreover, a number of substances derived from lipids are contained into platelets. Eicosanoids are lipid signaling mediators generated by the action of lipoxygenase and include prostaglandins, thromboxane A2, 12-hydroxyeicosatetraenoic acid. Isoprostanes have a chemical structure similar to this of prostanoids, but are differently produced into the particle, and are ligands for prostaglandins receptors, exhibiting biological activity like thromboxane A2. Endocannabinoids are derivatives from arachidonic acid which could reduce local pain. Phospholipids growth factors (sphingolipids, lysophosphatidic acid, platelet-activating factor) are involved in tissue

  10. Sexual behavior, cannibalism, and mating plugs as sticky traps in the orb weaver spider Leucauge argyra (Tetragnathidae). (United States)

    Aisenberg, Anita; Barrantes, Gilbert


    Unpublished field observations in Leucauge argyra, a tropical orb weaver spider, suggest the occurrence of conspicuous mating plugs that could reduce or prevent remating attempts. Otherwise, the sexual behavior of this species remains unknown. The aims of this study were to describe the courtship behavior and copulation in L. argyra and investigate mating plug formation in this species. Fourteen virgin females and 12 plugged females were exposed to up to three males and checked for mating plug formation. Of the 12 virgins that copulated, nine produced plugs (five immediately after copulation), and the five plugged females that copulated produced another mating plug immediately after copulation. We did not detect the transfer of any male substance during copulation but observed a whitish liquid emerging from female genital ducts. Plug formation was positively associated with male twanging during courtship. One virgin and four plugged females cannibalized males. In seven trials with virgins and in three trials with plugged females, the male's palp adhered to a substance that emerged from female genital ducts and spread on her genital plate. The male had to struggle energetically to free his glued palp; two of these males were cannibalized while trying to release their palps. Females seem to determine copulation duration by altering the timing of mating plug formation and through sexual cannibalism. This is the first case reported of a mating plug as a sticky trap for males.

  11. The Development and Research of Word Document Format-Checking Plug-in Based on VSTO%基于VSTO的word文档格式检查插件的开发与研究

    Institute of Scientific and Technical Information of China (English)



    随着无纸化办公的不断推进,Microsoft Office办公软件逐渐成为主要的办公工具。利用Word写作文档时,难免会出现各种格式和内容错误,人工校对错误难免产生疏漏。因此研究基于VSTO的文档格式自动化检查辅助插件能够帮助使用者检查相关错误。从VSTO的特性入手,首先分析了Word的对象层次模型,然后就标题格式检查、正文重复词组、段落格式化、表格信息校对等功能的实现进行了研究。%With the continuous advancement of paperless office, Microsoft Office software have gradually become the main of-fice tools. Using Word writing documents, there will inevitably be errors in various formats and contents, proofreading errors will inevitably produce omissions. Therefore, the research of document format-checking plug-ins based on VSTO can help users to check the errors. Beginning with the characteristics of VSTO, the object hierarchy model of Word is analyzed firstly. Then, the implementation of the title format-checking, the main body of repeated phrases, paragraph formatting, and Table information checking are studied.

  12. Antibody formation in pregnant women with maternal-neonatal human platelet antigen mismatch from a hospital in northern Taiwan. (United States)

    Yang, Wan-Hua; Cheng, Chuen-Sheng; Chang, Jin-Biou; Liu, Kuang-Ting; Chang, Junn-Liang


    Neonatal alloimmune thrombocytopenia (NAIT) is a clinical syndrome that resembles hemolytic disease of the newborn, affecting the platelets only. The thrombocytopenia results from the maternal alloantibodies reacting with specific human platelet antigens (HPAs) on the fetal platelets. Forty-four maternal plasma samples were screened for platelet alloantibodies using qualitative solid phase enzyme-linked immunosorbent assay (ELISA) commercial kit (LIFECODES Pakplus, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA), and both the maternal and the corresponding cord blood samples were genotyped (LIFECODES ThromboType, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA). HPA genotyping results correlated with the genetic frequencies in the Taiwan population. A total of 34 newborns (77.3%) had partial HPA genotyping mismatches with the corresponding mothers. The most common partial mismatches between mothers and neonates in HPA genotypes were 13 (29.5%) in both HPA-3b and HPA-15a, followed by 12 (27.3%) in HPA-15b, and 8 (18.2%) in HPA-3a. The frequencies of homozygotic mother with heterozygotic neonate were 15.9% in both HPA-3a and HPA-15b, 9.1% in HPA-15a, 6.8% in HPA-3b, and 2.3% in both HPA-2a and HPA-6a. In this study, maternal HPA antibodies were found in five samples, whereas HLA class I antibodies were found in seven maternal plasma samples from the antibody screen. The results from this study have demonstrated that HPA mismatch is not the main cause for the production of HPA alloantibodies.

  13. Adhesion, activation, and aggregation of blood platelets and biofilm formation on the surfaces of titanium alloys Ti6Al4V and Ti6Al7Nb. (United States)

    Walkowiak-Przybyło, M; Klimek, L; Okrój, W; Jakubowski, W; Chwiłka, M; Czajka, A; Walkowiak, B


    Titanium alloys are still on the top list of fundamental materials intended for dental, orthopedics, neurological, and cardiovascular implantations. Recently, a special attention has been paid to vanadium-free titanium alloy, Ti6Al7Nb, that seems to represent higher biocompatibility than traditional Ti6Al4V alloy. Surprisingly, these data are not thoroughly elaborated in the literature; particularly there is a lack of comparative experiments conducted simultaneously and at the same conditions. Our study fills these shortcomings in the field of blood contact and microbiological colonization. To observe platelets adhesion and biofilm formation on the surfaces of compared titanium alloys, fluorescence microscope Olympus GX71 and scanning electron microscope HITACHI S-3000N were used. Additionally, flow cytometry analysis of platelets aggregation and activation in the whole blood after contact with sample surface, as an essential tool for biomaterial thrombocompatibility assessment, was proposed. As a result of our study it was demonstrated that polished surfaces of Ti6Al7Nb and Ti6Al4V alloys after contact with whole citrated blood and E. coli bacterial cells exhibit a considerable difference. Overall, it was established that Ti6Al4V has distinct tendency to higher thrombogenicity, more excessive bacterial biofilm formation and notable cytotoxic properties in comparison to Ti6Al7Nb. However, we suggest these studies should be extended for other types of cells and biological objects.

  14. Revitalization of an Immature Permanent Mandibular Molar with a Necrotic Pulp Using Platelet-Rich Fibrin: A Case Report (United States)

    Shoba, Krishnamma; Aman, Shibu; Bharkavi, Srinivasan Kumar Indu


    Any insult to the pulp during its development causes cessation of dentin formation and root growth. Pulpal status and degree of root development are the decisive factors in the treatment approach. Various treatment options have been tried like surgery with root-end sealing, calcium hydroxide–apexification, placement of apical plug and regenerative endodontic procedures to induce apexogenesis. An ideal scenario for a necrosed tooth with immature root would be continued root development coupled with regeneration of pulp tissue. We report a case, where revitalization was done using Platelet-Rich Fibrin (PRF) as a scaffold in immature mandibular molar tooth. PMID:28050518

  15. Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling. (United States)

    Pozner, Roberto G; Ure, Agustín E; Jaquenod de Giusti, Carolina; D'Atri, Lina P; Italiano, Joseph E; Torres, Oscar; Romanowski, Victor; Schattner, Mirta; Gómez, Ricardo M


    Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by Junín virus (JUNV), a member of the arenaviridae family. Although a recently introduced live attenuated vaccine has proven to be effective, AHF remains a potentially lethal infection. Like in other viral hemorrhagic fevers (VHF), AHF patients present with fever and hemorrhagic complications. Although the causes of the bleeding are poorly understood, impaired hemostasis, endothelial cell dysfunction and low platelet counts have been described. Thrombocytopenia is a common feature in VHF syndromes, and it is a major sign for its diagnosis. However, the underlying pathogenic mechanism has not yet been elucidated. We hypothesized that thrombocytopenia results from a viral-triggered alteration of the megakaryo/thrombopoiesis process. Therefore, we evaluated the impact of JUNV on megakaryopoiesis using an in vitro model of human CD34+ cells stimulated with thrombopoietin. Our results showed that CD34+ cells are infected with JUNV in a restricted fashion. Infection was transferrin receptor 1 (TfR1)-dependent and the surface expression of TfR1 was higher in infected cultures, suggesting a novel arenaviral dissemination strategy in hematopoietic progenitor cells. Although proliferation, survival, and commitment in JUNV-infected cultures were normal, viral infection impaired thrombopoiesis by decreasing in vitro proplatelet formation, platelet release, and P-selectin externalization via a bystander effect. The decrease in platelet release was also TfR1-dependent, mimicked by poly(I:C), and type I interferon (IFN alpha/beta) was implicated as a key paracrine mediator. Among the relevant molecules studied, only the transcription factor NF-E2 showed a moderate decrease in expression in megakaryocytes from either infected cultures or after type I IFN treatment. Moreover, type I IFN-treated megakaryocytes presented ultrastructural abnormalities resembling the reported thrombocytopenic NF-E2(-/-) mouse

  16. 49 CFR 230.59 - Fusible plugs. (United States)


    ..., DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Boilers and Appurtenances Fusible Plugs § 230.59 Fusible plugs. If boilers are equipped with fusible plugs, the plugs shall be removed and cleaned of scale each time the boiler is washed but not less frequently than during every...

  17. The effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative peritoneal adhesion formation in rats. (United States)

    Makarchian, Hamid Reza; Kasraianfard, Amir; Ghaderzadeh, Pezhman; Javadi, Seyed Mohammad Reza; Ghorbanpoor, Manoochehr


    To assess the effectiveness of heparin, platelet-rich plasma (PRP), and silver nanoparticles on prevention of postoperative adhesion in animal models. Sixty males Albino Wistar rats aged 5 to 6 weeks were classified into five groups receiving none, heparin, PRP, silver nanoparticles, PRP plus silver nanoparticles intraperitoneally. After 2 weeks, the animals underwent laparotomy and the damaged site was assessed for peritoneal adhesions severity. The mean severity scores were 2.5 ± 0.9, 2.16 ± 0.7, 1.5 ± 0.5, 2.66 ± 0.88, and 2.25 ± 0.62 in the control, heparin, PRP, silver and PRP plus silver groups, respectively with significant intergroup difference (p = 0.004). The highest effective material for preventing adhesion formation was PRP followed by heparin and PRP plus silver. Moreover, compared to the controls, only use of PRP was significantly effective, in terms of adhesion severity (p = 0.01) . Platelet-rich plasma alone may have the highest efficacy for preventing postoperative peritoneal adhesions in comparison with heparin, silver nanoparticles and PRP plus silver nanoparticles.

  18. Acquired platelet function defect (United States)

    Acquired qualitative platelet disorders; Acquired disorders of platelet function ... blood clotting. Disorders that can cause problems in platelet function include: Idiopathic thrombocytopenic purpura Chronic myelogenous leukemia Multiple ...

  19. Platelet Donation (United States)

    ... of gratitude that washed over me when I saw those platelets going into my husband’s body. I ... Needles LGBTQ+ Donors Blood Donor Community SleevesUp Games Facebook Avatars and Badges Banners eCards Red Cross Information ...

  20. Investigation of the thrombin-generating capacity, evaluated by thrombogram, and clot formation evaluated by thrombelastography of platelets stored in the blood bank for up to 7 days

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar; Svendsen, M.S.; Salado, J.


    thrombin) and endogenous thrombin potential (ETP; nm thrombin*min) were registered. Clot formation was evaluated by TEG and the R time (min), maxial amplitude (MA; mm), time to maximum thrombus generation (TMG; min) and maximum thrombus generation (MTG; dynes cm(-2) s(-1)) and total thrombus generation...... (TTG; dyne cm(-2)) were registered. RESULTS: Platelets become more procoagulant, evaluated both by TEG and CAT during storage. The reduction in CAT lag time and the ttPeak correlated with a decrease in the TEG R time and TMG (P ....0035). No correlation between ETP and TTG was found (P = 0.65). CONCLUSION: The kinetics of thrombin generation, as evaluated by CAT, correlates with the thrombus generation, as evaluated by thrombelastography and this may in part explain the clinical utility of the TEG in identifying clinically relevant coagulopathies...

  1. Platelets, inflammation and tissue regeneration. (United States)

    Nurden, Alan T


    Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.

  2. Blood platelets in the progression of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Nina S Gowert

    Full Text Available Alzheimer's disease (AD is characterized by neurotoxic amyloid-ß plaque formation in brain parenchyma and cerebral blood vessels known as cerebral amyloid angiopathy (CAA. Besides CAA, AD is strongly related to vascular diseases such as stroke and atherosclerosis. Cerebrovascular dysfunction occurs in AD patients leading to alterations in blood flow that might play an important role in AD pathology with neuronal loss and memory deficits. Platelets are the major players in hemostasis and thrombosis, but are also involved in neuroinflammatory diseases like AD. For many years, platelets were accepted as peripheral model to study the pathophysiology of AD because platelets display the enzymatic activities to generate amyloid-ß (Aß peptides. In addition, platelets are considered to be a biomarker for early diagnosis of AD. Effects of Aß peptides on platelets and the impact of platelets in the progression of AD remained, however, ill-defined. The present study explored the cellular mechanisms triggered by Aß in platelets. Treatment of platelets with Aß led to platelet activation and enhanced generation of reactive oxygen species (ROS and membrane scrambling, suggesting enhanced platelet apoptosis. More important, platelets modulate soluble Aß into fibrillar structures that were absorbed by apoptotic but not vital platelets. This together with enhanced platelet adhesion under flow ex vivo and in vivo and platelet accumulation at amyloid deposits of cerebral vessels of AD transgenic mice suggested that platelets are major contributors of CAA inducing platelet thrombus formation at vascular amyloid plaques leading to vessel occlusion critical for cerebrovascular events like stroke.

  3. Platelet rich plasma promotes skeletal muscle cell migration in association with up-regulation of FAK, paxillin, and F-Actin formation. (United States)

    Tsai, Wen-Chung; Yu, Tung-Yang; Lin, Li-Ping; Lin, Mioa-Sui; Tsai, Ting-Ta; Pang, Jong-Hwei S


    Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The aim of this study was to investigate the effect and molecular mechanism of PRP on migration of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague-Dawley rats were treated with PRP. The cell migration was evaluated by transwell filter migration assay and electric cell-substrate impedance sensing. The spreading of cells was evaluated microscopically. The formation of filamentous actin (F-actin) cytoskeleton was assessed by immunofluorescence staining. The protein expressions of paxillin and focal adhesion kinase (FAK) were assessed by Western blot analysis. Transfection of paxillin small-interfering RNA (siRNAs) to muscle cells was performed to validate the role of paxillin in PRP-mediated promotion of cell migration. Dose-dependently PRP promotes migration of and spreading and muscle cells. Protein expressions of paxillin and FAK were up-regulated dose-dependently. F-actin formation was also enhanced by PRP treatment. Furthermore, the knockdown of paxillin expression impaired the effect of PRP to promote cell migration. It was concluded that PRP promoting migration of muscle cells is associated with up-regulation of proteins expression of paxillin and FAK as well as increasing F-actin formation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  4. Platelets promote bacterial dissemination in a mouse model of streptococcal sepsis. (United States)

    Kahn, Fredrik; Hurley, Sinead; Shannon, Oonagh


    Platelets have been reported to contribute to inflammation and inflammatory disorders. In the present study, we demonstrate that platelets contribute to the acute response to bacterial infection in a mouse model of invasive Streptococcus pyogenes infection. Thrombocytopenia occurred rapidly in infected animals and this was associated with platelet activation, formation of platelet-neutrophil complexes and neutrophil activation. In order to assess the role of platelets during infection, platelets were depleted prior to infection. Platelet-depleted animals had significantly decreased platelet-neutrophil complex formation and neutrophil activation in response to infection. Importantly, significantly fewer bacteria disseminated to the blood, lungs, and spleen of platelet-depleted animals. Platelet-depleted animals did not decrease as significantly in weight as the infected control animals. The results demonstrate a previously unappreciated role for platelets during the pathophysiological response to infection, whereby S. pyogenes bacteria bind to platelets and platelets facilitate bacterial dissemination.

  5. 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.

    Directory of Open Access Journals (Sweden)

    Andrezza C Chagas


    Full Text Available 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.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 (K(D 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.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.

  6. LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism. (United States)

    Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco


    Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. The NAHIF* Plug-in-Magnet

    CERN Multimedia

    CERN Audiovisual Unit


    * North Area High Intensity Facility of the CERN SPS. The beamlines with target stations and the plug-in magnets - The plug-in magnet to be removed for repair - The lifting bar and tool for the vacuum connector - The control stand - Controls for vacuum connector tool - The plug-in vacuum connector - Liftingbar with the automatic pins for magnets - The gravitational automatic pin - The plug-in kit in action.

  8. Efficacy of platelet-rich plasma gel and hyaluronan hydrogel as carriers of electrically polarized hydroxyapatite microgranules for accelerating bone formation. (United States)

    Ohba, Seiko; Wang, Wei; Itoh, Soichiro; Takagi, Yuzo; Nagai, Akiko; Yamashita, Kimihiro


    The technology for electrical polarization and characterization of hydroxyapatite (HA) microgranules has been developed. This study aimed to examine and compare the efficacy of composites comprising electrically polarized HA (pHA) microgranules and platelet-rich plasma (PRP) or hyaluronan (HAN) in osteoconductivity. Composites of HA microgranules with or without electrical polarization and either PRP or HAN (PRP+pHA, PRP+HA, HAN+pHA, and HAN+HA, respectively), as well as pHA and HA microgranules were implanted randomly into holes created in the medial femoral condyle or tibial tuberosity of rabbits. As a control, PRP or HAN gel alone was implanted, or the bone holes were left empty. Each group included six animals. After 6 weeks, histological examination was performed, and osteoclastic and osteoblastic cell activities were assessed by cell counting. Although PRP alone could not induce bone formation, PRP+pHA and PRP+HA composites, especially the former, activated osteogenic cells and enhanced bone formation. This effect was not prominent in the HAN+pHA and HAN+HA composites. PRP+HA composites formed a gel in which the ceramic particles were dispersed and entrapped in the fibrin network of PRP. It is assumed that these particles provide scaffolds for osteogenic cells, and when electrically polarized, can activate the cells in co-operation with the positive effects of the PRP, resulting in enhanced bone formation. Conversely, it is conceivable that this composite gel cannot act as an accelerator for woven bone formation, because HAN with low viscoelasticity is absorbed rapidly after implantation, the hydrated network containing HA microgranules is destroyed, and the HA microgranules effuse with HAN from the bone hole.

  9. How do the full-generation poly(amido)amine (PAMAM) dendrimers activate blood platelets? Activation of circulating platelets and formation of "fibrinogen aggregates" in the presence of polycations. (United States)

    Watala, Cezary; Karolczak, Kamil; Kassassir, Hassan; Talar, Marcin; Przygodzki, Tomasz; Maczynska, Katarzyna; Labieniec-Watala, Magdalena


    Direct use of poly(amido)amine (PAMAM) dendrimers as drugs may be limited, due to uncertain (cyto)toxicity. Peripheral blood components, which constitute the first line of a contact with administered pharmaceuticals, may become vastly affected by PAMAM dendrimers. The aim of this study was to explore how PAMAMs' polycationicity might affect blood platelet activation and reactivity, and thus trigger various haemostatic events. We monitored blood platelet reactivity in rats with experimental diabetes upon a long-term administration of the unmodified PAMAM dendrimers. In parallel, the effects on blood flow in a systemic circulation was recorded intravitally in mice administered with PAMAM G2, G3 or G4. Compounding was the in vitro approach to monitor the impact of PAMAM dendrimers on blood platelet activation and reactivity and on selected haemostatic and protein conformation parameters. We demonstrated the activating effects of polycations on blood platelets. Some diversity of the revealed outcomes considerably depended on the used approach and the particular technique employed to monitor blood platelet function. We discovered undesirable impact of plain PAMAM dendrimers on primary haemostasis and their prothrombotic influence. We emphasize the need of a more profound verifying of all the promising findings collected for PAMAMs with the use of well-designed in vivo preclinical studies.

  10. Platelet lipidomics: a modern day perspective on lipid discovery and characterization in platelets


    O’Donnell, Valerie B.; Murphy, Robert C.; Watson, Steve P.


    Lipids are diverse families of biomolecules that perform essential structural and signaling roles in platelets. Their formation and metabolism is tightly controlled by enzymes and signal transduction pathways, and their dysregulation leads to significant defects in platelet function and disease. Platelet activation is associated with significant changes to membrane lipids, and formation of diverse bioactive lipids that play essential roles in hemostasis. In recent years, new generation mass s...

  11. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta;


    formation and exocytosis in various cell types, but its exact function in platelets is not established. Here, we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild thrombocytopenia and a small increase in platelet size in mice. Unexpectedly, Cdc42-deficient platelets were able to form...... reduced, suggesting increased clearing of the cells under physiologic conditions. These data point to novel multiple functions of Cdc42 in the regulation of platelet activation, granule organization, degranulation, and a specific role in GPIb signaling....

  12. Platelet-rich plasma improves expansion of human mesenchymal stem cells and retains differentiation capacity and in vivo bone formation in calcium phosphate ceramics. (United States)

    Vogel, Julia P; Szalay, Krisztian; Geiger, Florian; Kramer, Martin; Richter, Wiltrud; Kasten, Philip


    Mesenchymal stem cells (MSC) applied to bone substitution materials can improve bone healing. Bone formation in biocomposites is highly dependent on the kind of biomaterial, its pre-treatment and the applied cells. Potentially immunogenic or infectious supplements such as fetal calf serum (FCS) should be avoided in cell expansion media. Therefore, we developed an expansion protocol free of xenogenic supplements. Cells expanded with two different media were tested on distinct biomaterials for their bone formation capacity after ectopic implantation in vivo, as well as for their growth rate and differentiation capacity in vitro. MSC of six donors were expanded with cell expansion medium containing FCS (2%) or platelet-rich plasma (PRP, 3%). Their growth rate and osteogenic, adipogenic and chondrogenic differentiation capacity were compared in vitro. For the in vivo bone formation assay, expanded cells (2 x 105 or 2 x 106) were seeded on calcium-deficient hydroxyapatite (CDHA; n = 12) and on beta-tricalcium phosphate (beta-TCP; n = 12) blocks, which had been coated with either fibronectin or human serum. They were then implanted subcutaneously in severe combined immunodeficient mice (SCID), harvested after 8 weeks and analysed by histology. Bone formation was assessed by a semi-quantitative bone score, after toluidine blue and alizarin red staining. Human cells were detected by an in situ hybridisation for human-specific alu sequences. PRP-supplemented expansion medium yielded two-fold higher cell numbers compared to medium with FCS (P = 0.046) after 3 weeks (four passages) and retained a similar capacity to differentiate towards the osteogenic, chondrogenic and adipogenic lineage. In vivo bone formation was equal for cells expanded with PRP and FCS and depended on the specific surface area of the carrier. CDHA (specific surface area (SSA) 48 m2/g) showed a significantly better bone formation in deep layers (P = 0.005) than beta-TCP (SSA 0.5 m2/g). Fibronectin

  13. SAMI Automated Plug Plate Configuration

    CERN Document Server

    Lorente, Nuria P F; Goodwin, Michael


    The Sydney-AAO Multi-object Integral field spectrograph (SAMI) is a prototype wide-field system at the Anglo-Australian Telescope (AAT) which uses a plug-plate to mount its 13 x 61-core imaging fibre bundles (hexabundles) in the optical path at the telescope's prime focus. In this paper we describe the process of determining the positions of the plug-plate holes, where plates contain three or more stacked observation configurations. The process, which up until now has involved several separate processes and has required significant manual configuration and checking, is now being automated to increase efficiency and reduce error. This is carried out by means of a thin Java controller layer which drives the configuration cycle. This layer controls the user interface and the C++ algorithm layer where the plate configuration and optimisation is carried out. Additionally, through the Aladin display package, it provides visualisation and facilitates user verification of the resulting plates.

  14. Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis. (United States)

    Koupenova, Milka; Vitseva, Olga; MacKay, Christopher R; Beaulieu, Lea M; Benjamin, Emelia J; Mick, Eric; Kurt-Jones, Evelyn A; Ravid, Katya; Freedman, Jane E


    Viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. Here, we show that infection with encephalomyocarditis virus (EMCV) rapidly reduces platelet count, and this response is attributed to platelet Toll-like receptor 7 (TLR7). Platelet-TLR7 stimulation mediates formation of large platelet-neutrophil aggregates, both in mouse and human blood. Intriguingly, this process results in internalization of platelet CD41-fragments by neutrophils, as assessed biochemically and visualized by microscopy, with no influence on platelet prothrombotic properties. The mechanism includes TLR7-mediated platelet granule release, translocation of P-selectin to the cell surface, and a consequent increase in platelet-neutrophil adhesion. Viral infection of platelet-depleted mice also led to increased mortality. Transfusion of wild-type, TLR7-expressing platelets into TLR7-deficient mice caused a drop in platelet count and increased survival post EMCV infection. Thus, this study identifies a new link between platelets and their response to single-stranded RNA viruses that involves activation of TLR7. Finally, platelet-TLR7 stimulation is independent of thrombosis and has implications to the host immune response and survival.

  15. Effect of osteogenic periosteal distraction by a modified Hyrax device with and without platelet-rich fibrin on bone formation in a rabbit model: a pilot study. (United States)

    Pripatnanont, P; Balabid, F; Pongpanich, S; Vongvatcharanon, S


    This study evaluated the effect of a modified Hyrax device and platelet-rich fibrin (PRF) on osteogenic periosteal distraction (OPD). Twelve adult male New Zealand white rabbits were separated into two main groups (six in each) according to the duration of the consolidation period (4 or 8 weeks). In each main group, the animals underwent OPD of the left and right sides of the mandible and were divided into four subgroups (three animals per group): device vs. device+PRF, and PRF vs. sham. Radiographic, histological, histomorphometric, and micro-computed tomography (micro-CT) analyses were performed. New bone formation was observed on the lateral and vertical sides of the mandible of all groups. Micro-CT and histomorphometry showed that the device+PRF group presented the highest percentages of bone volume and bone area at 4 weeks (56.67 ± 12.67%, 41.37 ± 7.57%) and at 8 weeks (49.67 ± 8.33%, 55.46 ± 10.67%; significantly higher than the other groups, P<0.001), followed by the device group at 4 weeks (33.00 ± 1.73%, 33.21 ± 11.00%) and at 8 weeks (30.00 ± 3.00%, 23.25 ± 5.46%). In conclusion, the modified Hyrax device was used successfully for OPD in a rabbit model to gain vertical ridge augmentation, and greater bone maturation was achieved with the addition of PRF.

  16. A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase: ex vivo and in vivo studies. (United States)

    Jayakumar, Thanasekaran; Chen, Wei-Fan; Lu, Wan-Jung; Chou, Duen-Suey; Hsiao, George; Hsu, Chung-Yi; Sheu, Joen-Rong; Hsieh, Cheng-Ying


    Sulforaphane is a naturally occurring isothiocyanate, which can be found in cruciferous vegetables such as broccoli and cabbage. Sulforaphane was found to have very potent inhibitory effects on tumor growth through regulation of diverse mechanisms. However, no data are available concerning the effects of sulforaphane on platelet activation and its relative issues. Activation of platelets caused by arterial thrombosis is relevant to a variety of cardiovascular diseases. Hence, the aim of this study was to examine the in vivo antithrombotic effects of sulforaphane and its possible mechanisms in platelet activation. Sulforaphane (0.125 and 0.25 mg/kg) was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice. Other in vivo studies also revealed that sulforaphane (0.25 mg/kg) significantly prolonged platelet plug formation in mice. In addition, sulforaphane (15-75 μM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen. Sulforaphane inhibited platelet activation accompanied by inhibiting relative Ca(2+) mobilization; phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs) and Akt; and hydroxyl radical (OH(●)) formation. Sulforaphane markedly increased cyclic (c)AMP, but not cyclic (c)GMP levels, and stimulated vasodilator-stimulated phosphoprotein (VASP) phosphorylation. SQ22536, an inhibitor of adenylate cyclase, but not ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxal in-1-one), an inhibitor of guanylate cyclase, obviously reversed the sulforaphane-mediated effects on platelet aggregation; PKC activation, p38 MAPK, Akt and VASP phosphorylation; and OH(●) formation. Furthermore, a PI3-kinase inhibitor (LY294002) and a p38 MAPK inhibitor (SB203580) both significantly diminished PKC activation and p38 MAPK and Akt phosphorylation; in contrast, a PKC inhibitor (RO318220) did not diminish p38 MAPK or Akt phosphorylation stimulated by collagen. This

  17. Halliburton Composite Bridge Plug Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Starbuck, J.M.; Luttrell, C.R.; Aramayo, G.


    The overall objectives of this CRADA were to assist Halliburton in analyzing a composite bridge plug and to determine why their original design was failing in the field. In Phase 1, finite element analyses were done on the original composite slip design and several alternative designs. The composite slip was the component in the bridge plug that was failing. The finite element code ABAQUS was used for these calculations and I-DEAS was used as the pre- and post-processor in the analyses. Several different designs and materials were analyzed and recommendations were made towards improving the design. In Phase 2, the objective was to develop finite element models that would accurately represent the deformations in the entire all-composite 4-1/2' diameter bridge plug assembly. The finite element code LS-DYNA was used and the results from this effort were intended to expand Halliburton's composite design and analysis capabilities with regard to developing future composite components for downhole tools. In addition to the finite element modeling, this effort involved the utilization of micromechanics to determine the necessary composite material properties that were needed as input for finite element codes.

  18. Interaction of clay and concrete plugs - Plugging of 5 m deep hole KA1621G01 at Aespoe

    Energy Technology Data Exchange (ETDEWEB)

    Pusch, Roland [Drawrite AB, Lund (Sweden); Luleaa Technical Univ., Luleaa (Sweden); Ramqvist, Gunnar [Eltekno AB, Figeholm (Sweden)


    along the contact between the plug and the borehole wall as well as interleaved within the bottom of the concrete fill. Chemical alteration of the cement mineral phases at the clay-concrete contact released some quantities of Ca and K that had partly replaced Na in the interlayer of the clay. Precipitation of gypsum and halite had occurred as well as chemical modifications of the clay. The cement has clearly been altered in contact with the clay plug and has lost part of the material strength. Neocrystallization of a fibrous Ca-Si phase had occurred along with the formation of some amorphous components. Dissolution in the saline water is the probable mechanism. The major practical consequence of the chemical interaction of contacting clay and concrete is that the clay becomes slightly less expandable and slightly more conductive within a few centimetres distance from the contact and that the concrete loses some of its strength in 3 years. The adhesion between concrete and rock appeared to be low and concrete plug segments could easily be extruded from the discs by hand.

  19. Single-step separation of platelets from whole blood coupled with digital quantification by interfacial platelet cytometry (iPC). (United States)

    Basabe-Desmonts, L; Ramstrom, S; Meade, G; O'Neill, S; Riaz, A; Lee, L P; Ricco, A J; Kenny, D


    IIbβ3) and, relevant to diagnostic applications, platelet adhesion correlates strongly with normal versus abnormal platelet function. A critical function of platelets is to adhere to regions of damage on blood vessel walls; in contrast to conventional flow cytometry, where platelets are suspended in solution, iPC enables physiologically relevant platelet bioassays based on platelet/protein-matrix interactions on surfaces. This technology should be inexpensive to implement in clinical assay format, is readily integrable into fluidic microdevices, and paves the way for high-throughput platelet assays from microliter volumes of whole blood.

  20. Ultrastructural studies of the gray platelet syndrome. (United States)

    White, J G


    The gray platelet syndrome (GPS) is a rare inherited disorder in which peripheral blood platelets are relatively large, vacuolated, and almost devoid of cytoplasmic granulation. In the present study we have evaluated the ultrastructure and cytochemistry of platelets from 2 patients with the GPS to determine precisely which organelles are missing from their cells. The findings indicate that gray platelets contain normal numbers of mitochondria, dense bodies, peroxisomes, and lysosomes but specifically lack alpha-granules. Preliminary studies of megakaryocytes from 1 of the 2 patients suggest that the defect in granule formation may lie at the level of the Golgi zone.

  1. Platelet Function Tests (United States)

    ... be limited. Home Visit Global Sites Search Help? Platelet Function Tests Share this page: Was this page helpful? ... their patients by ordering one or more platelet function tests. Platelet function testing may include one or more of ...

  2. Congenital platelet function defects (United States)

    ... storage pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... Congenital platelet function defects are bleeding disorders that ... function, even though there are normal platelet numbers. Most ...

  3. Borehole plugging by compaction process. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, R.; MacGowan, C.; Nolan, E.; Morey, R.; Palty, A.


    The requirements of an overall program to preserve the integrity of a repository formation are documented. The repository is intended to be in stable earth stratum used as a safe and permanent storage area for nuclear waste material. These wastes represent an environmental hazard for a period of up to 200,000 years. An engineering analysis, a reliability and quality-assurance program, and a development program for borehole plugging by compaction process, using natural earthen materials, are presented. Part 1 provides the engineering analysis of downhole compaction methods and related instrumentation along with a recommended development plan from concept through a pilot in-situ experiment. Part 2 provides a reliability and quality-assurance program from laboratory testing of materials through an in-situ experiment.

  4. Understanding platelet function through signal transduction. (United States)

    Lazarus, Alan H; Song, Seng; Crow, Andrew R


    Platelets are activated by a number of stimuli resulting in the expression and/or activation of surface receptors, secretion of vasoactive substances, adhesion, aggregation, and finally thrombus formation. These events are propagated by a process known as transmembrane signaling, which relays the activating signal from the platelet membrane (eg, von Willebrand Factor binding to glycoprotein Ib) to the inside of the platelet which then serves to activate the platelet via a cascade of biochemical interactions. Inhibition of these transmembrane signaling molecules with a variety of available inhibitors or antagonists can in many cases prevent the platelet from becoming activated. An awareness of the mechanisms involved in platelet transmembrane signaling and the recent availability of new reagents to inhibit signaling may provide us with additional means to prevent platelet activation and perhaps even ameliorate the platelet storage lesion. This review will provide an introduction to the field of platelet transmembrane signaling and give an overview of some of the platelet signaling mechanisms that are relevant to transfusion medicine. Copyright 2003, Elsevier Science (USA). All rights reserved.

  5. On the formation of narrowly polydispersed PMMA by surface initiated polymerization (SIP) from AIBN-coated/intercalated clay nanoparticle platelets. (United States)

    Fan, Xiaowu; Xia, Chuanjun; Advincula, Rigoberto C


    Various free radical surface initiated polymerization (SIP) conditions were investigated on clay nanoparticles coated with monocationic 2,2'-azobisisobutyronitrile (AIBN) type free radical initiators. Interesting differences in the mechanism of polymer nanocomposite product formation and the role of nanoparticle surface bound AIBN initiators were observed on three types of poly(methyl methacrylate) (PMMA) polymerization conditions: bulk, suspension, and solution. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) measurements confirmed the attachment of the initiator on the clay particles without decomposition of the azo group. XRD and transmission electron microscopy (TEM) showed that a well-dispersed structure was accomplished only by bulk and solution SIP. The suspension SIP product consisted of a partially exfoliated structure as shown by XRD and clay particle aggregate formation as shown by TEM. In general, the molecular weights (MWs) of the surface bound polymers were found to be lower than those of the free polymer. Using the same clay loading and initiator concentrations, we observed that relatively higher MW polymers were obtained from suspension and bulk polymerizations in contrast to solution method. However, the most interesting observation is that the surface bound polymers (on all three conditions) showed much narrower polydispersity compared to that of a typical AIBN type free radical polymerization.

  6. Effect of platelet-derived growth factor-BB on bone formation in calvarial defects: an experimental study in rabbits

    DEFF Research Database (Denmark)

    Vikjaer, D; Blom, S; Hjørting-Hansen, E


    with expanded polytetrafluoroethylene membranes to prevent interference with osteogenesis within the defect by the surrounding tissue and to keep the growth factor in place. A single dose of methylcellulose gel (4.4%) with (n = 8) or without rhPDGF-BB (50 micrograms/ml) (n = 8) was applied to the defects......, and the bone formation was evaluated after 8 weeks. Healing of defects in both groups was characterized by the presence of newly formed bone along the edges of the original defect and by a central area of fibrous connective tissue. The newly formed bone in the rhPDGF-BB treated defects had a trabecular...... of bone marrow was increased 75% in the rhPDGF-BB-treated defect. The porosity of cortical lamella in the newly formed bone was 84% higher in the rhPDGF-BB-treated defects compared to the control. These results show that administration of a single dose of rhPDGF-BB stimulates bone formation in critical...

  7. Physiopathology of blood platelets and development of platelets substitutes. Progress report, August 1, 1976--October 31, 1977. [/sup 51/Cr

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, M G


    Progress is reported on the following research projects: the effect of estrogen on platelet aggregability and thrombus formation; the antithrombotic effect of platelet inhibiting agents in a bench model of artificial kidney; the arrest of hemorrhage in severely alloimmunized thrombocytopenic patients; and in vivo elution of /sup 51/Cr from labeled platelets induced by antibody. (HLW)

  8. Platelet dynamics in three-dimensional simulation of whole blood. (United States)

    Vahidkhah, Koohyar; Diamond, Scott L; Bagchi, Prosenjit


    A high-fidelity computational model using a 3D immersed boundary method is used to study platelet dynamics in whole blood. We focus on the 3D effects of the platelet-red blood cell (RBC) interaction on platelet margination and near-wall dynamics in a shear flow. We find that the RBC distribution in whole blood becomes naturally anisotropic and creates local clusters and cavities. A platelet can enter a cavity and use it as an express lane for a fast margination toward the wall. Once near the wall, the 3D nature of the platelet-RBC interaction results in a significant platelet movement in the transverse (vorticity) direction and leads to anisotropic platelet diffusion within the RBC-depleted zone or cell-free layer (CFL). We find that the anisotropy in platelet motion further leads to the formation of platelet clusters, even in the absence of any platelet-platelet adhesion. The transverse motion, and the size and number of the platelet clusters are observed to increase with decreasing CFL thickness. The 3D nature of the platelet-RBC collision also induces fluctuations in off-shear plane orientation and, hence, a rotational diffusion of the platelets. Although most marginated platelets are observed to tumble just outside the RBC-rich zone, platelets further inside the CFL are observed to flow with an intermittent dynamics that alters between sliding and tumbling, as a result of the off-shear plane rotational diffusion, bringing them even closer to the wall. To our knowledge, these new findings are based on the fundamentally 3D nature of the platelet-RBC interaction, and they underscore the importance of using cellular-scale 3D models of whole blood to understand platelet margination and near-wall platelet dynamics.

  9. Mating plugs in polyandrous giants: which sex produces them, when, how and why?

    Directory of Open Access Journals (Sweden)

    Matjaž Kuntner

    Full Text Available BACKGROUND: Males usually produce mating plugs to reduce sperm competition. However, females can conceivably also produce mating plugs in order to prevent unwanted, superfluous and energetically costly matings. In spiders-appropriate models for testing plugging biology hypotheses-mating plugs may consist of male genital parts and/or of amorphous covers consisting of glandular or sperm secretions. In the giant wood spider Nephila pilipes, a highly sexually dimorphic and polygamous species, males are known to produce ineffective embolic plugs through genital damage, but nothing is known about the origin and function of additional conspicuous amorphous plugs (AP covering female genitals. METHODOLOGY: We tested alternative hypotheses of the nature and function of AP in N. pilipes by staging mating trials with varying degrees of polyandry. No APs were ever formed during mating trials, which rules out the possibility of male AP formation. Instead, those females that oviposited produced the AP from a liquid secreted during egg sac formation. Polyandrous females were more likely to lay eggs and to produce the AP, as were those that mated longer and with more total insertions. Our further tests revealed that, in spite of being a side product of egg sac production, AP, when hardened, prevented any subsequent copulation. CONCLUSIONS: We conclude that in the giant wood spider (Nephila pilipes, the amorphous mating plugs are not produced by the males, that repeated copulations (most likely polyandrous are necessary for egg fertilization and AP formation, and that the AP represents a female adaptation to sexual conflict through prevention of unwanted, excessive copulations. Considering the largely unknown origin of amorphous plugs in spiders, we predict that a similar pattern might be detected in other clades, which would help elucidate the evolutionary interplay of various selection pressures responsible for the origin and maintenance of mating plugs.

  10. Platelet activation determines the severity of thrombocytopenia in dengue infection (United States)

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit


    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  11. Plug Load Behavioral Change Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Metzger, I.; Kandt, A.; VanGeet, O.


    This report documents the methods and results of a plug load study of the Environmental Protection Agency's Region 8 Headquarters in Denver, Colorado, conducted by the National Renewable Energy Laboratory. The study quantified the effect of mechanical and behavioral change approaches on plug load energy reduction and identified effective ways to reduce plug load energy. Load reduction approaches included automated energy management systems and behavioral change strategies.

  12. Mitigation of Syngas Cooler Plugging and Fouling

    Energy Technology Data Exchange (ETDEWEB)

    Bockelie, Michael J. [Reaction Engineering International, Salt Lake City, UT (United States)


    understanding of deposit formation mechanisms; • performing Techno-Economic-Analysis for a representative IGCC plant to investigate the impact on plant economics, in particular the impacts on the Cost of Electricity (COE), due to plant shutdowns caused by syngas cooler plugging and fouling and potential benefits to plant economics of developing strategies to mitigate syngas cooler fouling; and • performing modeling and pilot scale tests to investigate the potential benefits of using a sorbent (fuel additive) to capture the vaporized metals that result in syngas cooler fouling. All project milestones for BP 1 and BP 2 were achieved. DOE was provided a briefing on our accomplishments in BP1 and BP2 and our proposed plans for Budget Period 3 (BP 3). Based on our research the mitigation technology selected to investigate in BP 3 was the use of a sorbent that can be injected into the gasifier with the fuel slurry to capture vaporized metals that lead to the deposit formation in the syngas cooler. The work effort proposed for BP 3 would have focused on addressing concerns raised by gasification industry personnel for the impacts on gasifier performance of sorbent injection, so that at the end of BP 3 the use of sorbent injection would be at “pre-commercial” stage and ready for use in a Field Demonstration that could be funded by industry or DOE. A Budget Continuation Application (BCA) was submitted to obtain funding for BP3 DOE but DOE chose to not fund the proposed BP3 effort.

  13. Multimeediaetendus : Opera Gets Plugged / Eve Arpo

    Index Scriptorium Estoniae

    Arpo, Eve


    Eesti Muusika- ja Teatriakadeemia lühiooperite õhtul "Opera Gets Plugged" etendunud lavastustest - Monika Mattieseni "DMeeter" ja Age Hirve "Tuleloitsija": Mõlema lavastaja ja projektijuht Liis Kolle

  14. Multimeediaetendus : Opera Gets Plugged / Eve Arpo

    Index Scriptorium Estoniae

    Arpo, Eve


    Eesti Muusika- ja Teatriakadeemia lühiooperite õhtul "Opera Gets Plugged" etendunud lavastustest - Monika Mattieseni "DMeeter" ja Age Hirve "Tuleloitsija": Mõlema lavastaja ja projektijuht Liis Kolle

  15. Function of eltrombopag-induced platelets compared to platelets from control patients with immune thrombocytopenia. (United States)

    Haselboeck, Johanna; Kaider, Alexandra; Pabinger, Ingrid; Panzer, Simon


    Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.

  16. A platelet monoclonal antibody inhibition assay for detection of glycoprotein IIb/IIIa-related platelet alloantibodies. (United States)

    Reiner, A P; Teramura, G; Nelson, K A; Slichter, S J


    Post-transfusion purpura (PTP) and neonatal alloimmune thrombocytopenia (NAT) result from formation of alloantibodies to platelet membrane glycoprotein-associated antigens. The detection and identification of platelet-specific alloantibodies in patient sera is often complicated by the presence of co-existing HLA antibodies and/or more than one platelet specificity in the same serum. We describe a solid phase assay that specifically detects antibodies to platelet membrane associated alloantigens by measuring the ability of patient antisera to inhibit the binding of glycoprotein GPIIb or GPIIIa monoclonal antibodies to intact platelets. When tested in the GPIIIa assay against a panel of random platelet donors, the reactivities of two known PLAI antisera that also contained different HLA antibodies were highly correlated (r = 0.99) and allowed PLA phenotyping of the population. A standard direct binding platelet ELISA, on the other hand, was unable to accurately PLA phenotype the same population. The reactivities of two known Baka antisera (one containing additional anti-PLA2 and the other anti-Brb specificities) were highly correlated (r = 0.95) in the GPIIb assay, and Bak phenotype determination was similarly accomplished for a random platelet panel. Furthermore, a comparison of platelet phenotype results (using the monoclonal inhibition assay) and genotype results (using DNA analysis) for the PLA and Bak systems showed a concordance of 98% for 146 alleles tested. In conclusion, the platelet monoclonal antibody inhibition assay: (1) allows determination of platelet-specific alloantibodies in the presence of contaminating HLA antibodies and/or in sera containing multiple platelet alloantibodies; (2) allows accurate platelet phenotyping for the GPIIIa-associated PLA and GPIIb-associated Bak antigen systems; and (3) may be applicable to the detection of other known or even novel platelet glycoprotein-associated antigens.

  17. Oscillation of an isolated liquid plug inside a dry capillary (United States)

    Srinivasan, Vyas; Kumar, Siddhartha; Asfer, Mohammed; Khandekar, Sameer


    The present work reports an experimental study on the dynamics of partially wetting isolated liquid plug (DI water), which is made to oscillate inside a square, glass capillary tube (1 mm × 1 mm; 60 mm length). The liquid plug is made to oscillate pneumatically at two different frequencies (0.25 and 0.35 Hz), using a cam-follower mechanism. Bright field imaging is used to visualize the three-phase contact line behavior, while, micro-Particle Imaging Velocimetry (PIV) apparatus is used to discern the nature of flow inside the oscillating liquid plug. During a cycle, due to the partial wetting nature of DI water, the three-phase contact line at the menisci gets pinned at the extreme end of each stroke, where the dynamic apparent contact angle gets drastically altered before the initiation of the next stroke. The difference between the apparent contact angle of the front and rear meniscus are seen to be a function of the oscillating frequency; the difference increasing with increasing frequency. The flow inside the liquid plug reveals unique non-Poiseuille flow features near the meniscus, due to free-slip boundary condition, which leads to formation of distinct vortex pairs behind it. The vortices too change their direction during each stroke of the oscillation, eventually leading to an alternating recirculation pattern inside the plug. The results clearly indicate that improved mathematical models are required for predicting transport parameters in such flows, which are important in engineering systems such as pulsating heat pipes, lab-on-chip devices and PEM fuel cells.

  18. Pneumococcal association to platelets is mediated by soluble fibrin and supported by thrombospondin-1. (United States)

    Niemann, Silke; Kehrel, Beate E; Heilmann, Christine; Rennemeier, Claudia; Peters, Georg; Hammerschmidt, Sven


    Platelets and coagulation are involved in bacterial colonisation of the host. Streptocococcus pneumoniae (pneumococcus) are important etiologic agents of respiratory tract infections in humans. The formation of pneumococci-platelet associations may facilitate haematogenous dissemination of pneumococci by providing an adhesive surface on damaged endothelium. However, the formation of platelet-pneumococci associations and the factors involved in this process have not been described so far. The formation of platelet-pneumococci associates was analysed and quantified using flow cytometry. Binding of pneumococci to platelets was significantly increased after activation of platelets with thrombin, while platelet activation by ADP or collagen did not promote formation of platelet-pneumococci associates. In addition to be a platelet agonist, thrombin cleaves fibrinogen, which results in the generation of fibrin. The simultaneous formation of fibrin and activation of platelets was shown to be a prerequisite for a high number of platelet-pneumococci associates. Moreover, exogenously added human thrombospondin-1 (TSP-1) significantly enhanced the association of pneumococci with activated platelets. Soluble fibrin and TSP-1 are key co-factors of platelet-pneumococci-association. Similar results were recently demonstrated for S. aureus-platelet adhesion. Consequently, we hypothesise that the described mechanism of platelet-bacteria-association might represent a general and important strategy of Gram-positive bacteria during development of invasive diseases.

  19. Platelet matching for alloimmunized patients

    Institute of Scientific and Technical Information of China (English)

    S H.Hsu


    @@ Platelets play an essential role in blood coagulation,hemostasis and maintenance of vascular integrity.Platelets are utilized primarily to prevent or treat bleeding in thrombocytopenic patients and patients with impaired platelet production in the bone marrow and/or with dysfunctional platelets.In current practice,platelet transfusion begins with randomly selected platelet products:either pooled platelets prepared from whole blood derived platelets; or single donor platelets prepared by apheresis procedures.

  20. Roll, adhere, spread and contract: structural mechanics of platelet function. (United States)

    Sorrentino, Simona; Studt, Jan-Dirk; Medalia, Ohad; Tanuj Sapra, K


    Platelets are involved in life-sustaining processes such as hemostasis, wound healing, atherothrombosis and angiogenesis. Mechanical trauma to blood vessels causes platelet activation resulting in their adherence and clot formation at the damaged site, culminating in clot retraction and tissue repair. Two of the major players underlying this process are the cytoskeleton, i.e., actin and microtubules, and the membrane integrin receptors. Rare congenital bleeding disorders such as Glanzmann thrombasthenia and Bernard-Soulier syndrome are associated with genetic alterations of platelet surface receptors, also affecting the platelet cytoskeletal structure. In this review, we summarize the current knowledge about platelet structure and adhesion, and delve into the mechanical aspects of platelet function. Platelets lack a nucleus, and can thus provide a minimal model of a biological cell. New biophysical tools may help to scrutinize platelets anew and to extend the existing knowledge on cell biology.

  1. Unaltered Angiogenesis-Regulating Activities of Platelets in Mild Type 2 Diabetes Mellitus despite a Marked Platelet Hyperreactivity (United States)

    Miao, Xinyan; Zhang, Wei; Huang, Zhangsen


    Type 2 diabetes mellitus (T2DM) is associated with platelet dysfunction and impaired angiogenesis. Aim of the study is to investigate if platelet dysfunction might hamper platelet angiogenic activities in T2DM patients. Sixteen T2DM patients and gender/age-matched non-diabetic controls were studied. Flow cytometry and endothelial colony forming cell (ECFC) tube formation on matrigel were used to assess platelet reactivity and angiogenic activity, respectively. Thrombin receptor PAR1-activating peptide (PAR1-AP) induced higher platelet P-selectin expression, and evoked more rapid and intense platelet annexin V binding in T2DM patients, seen as a more rapid increase of annexin V+ platelets (24.3±6.4% vs 12.6±3.8% in control at 2 min) and a higher elevation (30.9±5.1% vs 24.3±3.0% at 8 min). However, PAR1-AP and PAR4-AP induced similar releases of angiogenic regulators from platelets, and both stimuli evoked platelet release of platelet angiogenic regulators to similar extents in T2DM and control subjects. Thus, PAR1-stimulated platelet releasate (PAR1-PR) and PAR4-PR similarly enhanced capillary-like network/tube formation of ECFCs, and the enhancements did not differ between T2DM and control subjects. Direct supplementation of platelets to ECFCs at the ratio of 1:200 enhanced ECFC tube formation even more markedly, leading to approximately 100% increases of the total branch points of ECFC tube formation, for which the enhancements were also similar between patients and controls. In conclusion, platelets from T2DM subjects are hyperreactive. Platelet activation induced by high doses of PAR1-AP, however, results in similar releases of angiogenic regulators in mild T2DM and control subjects. Platelets from T2DM and control subjects also demonstrate similar enhancements on ECFC angiogenic activities. PMID:27612088

  2. Vascular plugs – A key companion to Interventionists – ‘Just Plug it’ (United States)

    Ramakrishnan, Sivasubramanian


    Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory. PMID:26304581

  3. Mastering Eclipse plug-in development

    CERN Document Server

    Blewitt, Alex


    If you are a Java developer who is familiar with the Eclipse plug-in environment, this book covers the advanced concepts that you need to know to achieve true expertise. Prior experience in creating Eclipse plug-ins is assumed for this book.

  4. Tension free femoral hernia repair with plug

    Directory of Open Access Journals (Sweden)

    Milivoje Vuković


    Conclusions: The technique of closing the femoral canal with plug a simple. The plug is made from monofilament material and is easily formed. This technique allows the reduction of recurrence and can be used safely, quickly and easily in elective and emergency situations.

  5. Mapping nanocavities in plugged SBA-15 with confined silver nanostructures

    NARCIS (Netherlands)

    De Lima Oliveira, Rafael; Shakeri, Mozaffar; Meeldijk, Johannes D.; de Jong, Krijn P.; de Jongh, Petra E.


    Silver nanostructures inside the pores of SBA-15 and plugged SBA-15 were synthesized and imaged, providing for the first time quantitative information about the nanocavity dimensions and plug distributions in plugged SBA-15.

  6. Platelet satellitism in infectious disease? (United States)

    Laskaj, Renata; Sikiric, Dubravka; Skerk, Visnja


    Background Platelet satellitism is a phenomenon of unknown etiology of aggregating platelets around polymorphonuclear neutrophils and other blood cells which causes pseudothrombocytopenia, visible by microscopic examination of blood smears. It has been observed so far in about a hundred cases in the world. Case subject and methods Our case involves a 73-year-old female patient with a urinary infection. Biochemical serum analysis (CRP, glucose, AST, ALT, ALP, GGT, bilirubin, sodium, potassium, chloride, urea, creatinine) and blood cell count were performed with standard methods on autoanalyzers. Serum protein fractions were examined by electrophoresis and urinalysis with standard methods on autoanalyzer together with microscopic examination of urine sediment. Erythrocyte sedimentation rate, blood culture and urine culture tests were performed with standard methods. Results Due to typical pathological values for bacterial urinary infection, the patient was admitted to the hospital. Blood smear examination revealed phenomenon, which has persisted for three weeks after the disease has been cured. Blood smears with EDTA as an anticoagulant had platelet satellitism whereas the phenomenon was not observed in tubes with different anticoagulants (Na, Li-heparin) and capillary blood. Discussion We hypothesize that satellitism was induced by some immunological mechanism through formation of antibodies which have mediated platelets binding to neutrophil membranes and vice versa. Unfortunately we were unable to determine the putative trigger for this phenomenon. To our knowledge this is the second case of platelet satellitism ever described in Croatia. PMID:26110042

  7. Plug-in Hybrid Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Angie; Moore, Ray; Rowden, Tim


    Our main project objective was to implement Plug-in Electric Vehicles (PEV) and charging infrastructure into our electric distribution service territory and help reduce barriers in the process. Our research demonstrated the desire for some to be early adopters of electric vehicles and the effects lack of education plays on others. The response of early adopters was tremendous: with the initial launch of our program we had nearly 60 residential customers interested in taking part in our program. However, our program only allowed for 15 residential participants. Our program provided assistance towards purchasing a PEV and installation of Electric Vehicle Supply Equipment (EVSE). The residential participants have all come to love their PEVs and are more than enthusiastic about promoting the many benefits of driving electric.

  8. Plug into 'the modernizing machine'!

    DEFF Research Database (Denmark)

    Krejsler, John B.


    ‘The modernizing machine’ codes individual bodies, things and symbols with images from New Public Management, neoliberal and Knowledge Economy discourses. Drawing on Deleuze & Guattari’s concept of machines, this article explores how ‘the modernizing machine’ produces neo-liberal modernization...... of the public sector. Taking its point of departure in Danish university reform, the article explores how the university is transformed by this desiring-producing machine. ‘The modernizing machine’ wrestles with the so-called ‘democratic-Humboldtian machine’. The University Act of 2003 and the host of reforms...... bodies and minds simultaneously produce academic subjectivities by plugging into these transformative machinic forces and are produced as they are traversed by them. What is experienced as stressful closures vis-à-vis new opportunities depends to a great extent upon how these producing...

  9. Friction pull plug welding: dual chamfered plate hole (United States)

    Coletta, Edmond R. (Inventor); Cantrell, Mark A. (Inventor)


    Friction Pull Plug Welding (FPPW) is a solid state repair process for defects up to one inch in length, only requiring single sided tooling (OSL) for usage on flight hardware. Early attempts with FPPW followed the matching plug/plate geometry precedence of the successful Friction Push Plug Welding program, however no defect free welds were achieved due to substantial plug necking and plug rotational stalling. The dual chamfered hole has eliminated plug rotational stalling, both upon initial plug/plate contact and during welding. Also, the necking of the heated plug metal under a tensile heating/forging load has been eliminated through the usage of the dual chamfered plate hole.

  10. Space maintenance in autogenous fresh demineralized tooth blocks with platelet-rich plasma for maxillary sinus bone formation: a prospective study. (United States)

    Kim, Eun-Suk; Kang, Ji-Yeon; Kim, Jae-Jin; Kim, Kyoung-Won; Lee, Eun-Young


    This prospective study evaluated the effectiveness of autogenous fresh demineralized tooth block (Auto-FDT block) with platelet-rich plasma (PRP) for maxillary sinus augmentation with simultaneous implant installation. Auto-FDT block with PRP was used in Group 1 (n = 15) and combined graft (allograft and xenograft) powder with PRP was used in Group 2 (n = 15). For up to 2 years after the final prosthesis was installed, clinical and radiographic examinations were performed to evaluate the amount of graft materials, residual alveolar height (RAH), sinus height (SH) after grafting, augmented graft height (AGH) and resorption height (RH). In ten cases, biopsies were harvested for histological and histomorphometric analyses. A total of 59 implants were placed in a severe atrophic posterior maxilla with less than 5 mm of RAH and sinus augmentation. None of the patients developed sinusitis or other complications, such as implant loss. The graft material extracted included one molar (or 2 premolars) in Group 1 and 1.8 cc in Group 2. The radiologic examination revealed the following average between-group difference SH (Group 1, 14.12 ± 1.63 mm vs Group 2, 16.51 ± 1.29 mm) and AGH (Group 1, 11.62 ± 2.22 mm vs Group 2, 13.65 ± 1.35 mm). However, sufficient SH and AGH were observed for the implants in the Auto-FDT block group. Two years after final prosthesis was installed, no between-group difference in the RH was observed (Group 1, 1.23 ± 0.73 mm vs Group 2, 1.77 ± 0.54 mm, P = 0.021). The histomorphometric analysis revealed no between-group difference in the new bone volume (Group 1, 23.13 ± 1.42 % vs Group 2, 24.18 ± 2.19 %, P = 0.548). The results showed that Auto-FDT block with PRP can be used in grafted sinuses for implants with only one extracted molar (or two premolars). Auto-FDT block with PRP promotes new bone formation that is comparable with combined grafts. Auto-FDT block with PRP is as an alternative to bone grafting

  11. Erythrocyte-platelet interaction in uncomplicated pregnancy. (United States)

    Swanepoel, Albe C; Pretorius, Etheresia


    Maternal and fetal requirements during uncomplicated pregnancy are associated with changes in the hematopoietic system. Platelets and erythrocytes [red blood cells (RBCs)], and especially their membranes, are involved in coagulation, and their interactions may provide reasons for the changed hematopoietic system during uncomplicated pregnancy. We review literature regarding RBC and platelet membrane structure and interactions during hypercoagulability and hormonal changes. We then study interactions between RBCs and platelets in uncomplicated pregnancy, as their interactions may be one of the reasons for increased hypercoagulability during uncomplicated pregnancy. Scanning electron microscopy was used to study whole blood smears from 90 pregnant females in different phases of pregnancy. Pregnancy-specific interaction was seen between RBCs and platelets. Typically, one or more platelets interacted through platelet spreading and pseudopodia formation with a single RBC. However, multiple interactions with RBCs were also shown for a single platelet. Specific RBC-platelet interaction seen during uncomplicated pregnancy may be caused by increased estrogen and/or increased fibrinogen concentrations. This interaction may contribute to the hypercoagulable state associated with healthy and uncomplicated pregnancy and may also play a fundamental role in gestational thrombocytopenia.

  12. [Changes in platelet function in children with acute or chronic tonsillitis]. (United States)

    Kirichuk, V F; Mareev, O V; Diudina, O Iu


    Children with a compensated or uncompensated form of acute or chronic tonsillitis demonstrate high platelet aggregation resultant in faster formation of platelet aggregates, an increased maximum size of these aggregates, faster achievement of the maximum platelet aggregation. Local drug therapy, combined drug + ultrasound and laser therapy failed to normalize platelet aggregation. The best effect on platelet aggregation was obtained in combined treatment with ultrasound and laser.


    Directory of Open Access Journals (Sweden)

    Prasantha Kumar Thankappan


    Full Text Available BACKGROUND Stroke is a major cause of long term morbidity and mortality. Several factors are known to increase the liability to stroke. Platelets play a crucial role in the pathogenesis of atherosclerotic complications, contributing to thrombus formation. Platelet size (mean platelet volume, MPV is a marker and possible determinant of platelet function, large platelets being potentially more reactive. Hence an attempt has-been made to study the association if any between mean platelet volume and thrombotic stroke. The aim of this study was to determine whether an association exists between Mean Platelet Volume (MPV and thrombotic stroke. MATERIALS AND METHODS The study is a case control study and data was collected at Government Medical College Hospital, Kottayam, Kerala a tertiary care referral centre. The study was carried out among fifty patients diagnosed with thrombotic stroke and presenting to the hospital within forty eight hours of onset of symptoms. Fifty age group and sex matched controls were also recruited. Mean platelet volume was obtained using a SYSMEX automated analyser. RESULTS This study has shown a statistically significant relation between mean platelet volume and risk of thrombotic stroke but no statistically significant correlation between clinical severity of stroke and mean platelet volume. CONCLUSION This study has shown an elevation of MPV in acute phase of thrombotic stroke. Platelet mass was found to be more or less a constant. This study did not find a statistically significant correlation between clinical severity of stroke and mean platelet volume.

  14. The expression levels of platelet adhesive receptors in PRP derived platelet concentrates during storage

    Directory of Open Access Journals (Sweden)

    Fatemeh Nassaji


    Full Text Available Background: Major platelet adhesive receptors that contribute significantly to thrombus formation include platelet receptor glycoprotein Ibα (GPIbα of the GPIb-IX-V complex and platelet glycoprotein VI (GPVI. GPIbα plays a crucial role in platelet tethering to sub-endothelial matrix, which initiates thrombus formation at arterial shear rates, whereas GPVI is critically involved in platelets firm adhesion to the site of injury regardless of shear condition. During storage, platelets experience some changes that deleteriously affect the expression levels of platelet receptors, which in turn can alter platelet functional behaviors. Considering the important roles of GPIbα and GPVI in platelet adhesion, it seems that any dramatic changes in the expression levels of these receptors can influence adhesive function of transfused platelets. Thereby examining GPIbα and GPVI expression during the storage of platelet concentrates may provide some useful information about the functional quality of these products after transfusion. Methods: In our experimental study, 5 PRP-platelet concentrates were randomly obtained from Iranian Blood Transfusion Organization (IBTO. All the platelet products met the standard quality assessment based on AABB (American Association of Blood Banks guidelines. Washed platelets were subjected to flowcytometry analysis for the evaluation of GPIbα and GPVI receptor expression in day 1, 3 and 5 after storage. Data were presented as mean fluorescence intensity (MFI and analyzed by Kruskal-Wallis test with Dunn’s multiple comparison test. Results: The GPIbα expression on first day (MFI=86±5.9 was reduced three days after storage (MFI= 69±6.9. The expression levels continued to reduce until day 5 in which GPIbα expression was markedly decreased to (MFI= 61±7.7 (P= 0.0094. GPVI expression on the days 1, 3 and 5 after storage were 20.6±3.3, 24±2.5 and 14±4.9, respectively. The results showed a significant decrease of

  15. Platelet thrombosis in cardiac-valve prostheses

    Energy Technology Data Exchange (ETDEWEB)

    Dewanjee, M.K.


    The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue valves in our one-day study in the dog model was similar (< 1% if injected In-111 platelets = 5 billion platelets). As the fibrous ingrowth covered the sewing ring, the thrombus formation decreased significantly. Only a small amount of thrombus was found on the leaflets at one month in both the dog and calf models. 38 refs., 9 figs., 5 tabs.

  16. Clinical application of radiolabelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, C. (Medical Univ. Lubeck, Lubeck (DE))


    This book presents papers on the clinical applications of radiolabelled platelets. The papers are grouped into six sections on platelet labelling techniques, radiolabelled platelets in cardiology, monitoring of antiplatelet therapy, platelet scintigraphy in stroke patients, platelet scintigraphy in angiology, and platelet scintigraphy in hematology and other clinical applications, including renal transplant rejection.

  17. Study for the Correlation between two tube-sealing fluids and formation of tube excrescence and tube-plugging%两种冲封管方式与锁骨下中心静脉置管导管内赘生物形成及堵管率关系的研究

    Institute of Scientific and Technical Information of China (English)

    王会英; 董风岐; 胡晶敏


    目的 探讨肝素钠溶液与生理盐水冲封管方式在锁骨下中心静脉置管(锁穿)导管内赘生物形成及导管堵管率方面的差异.方法 将126例腹部肿瘤锁穿患者按置管顺序随机分为肝素钠组(62人)和生理盐水组(64人),分别给予6~8 ml肝素钠溶液(浓度为50 U/ml)、生理盐水脉冲式冲封管.比较两种冲封管溶液引起的导管内赘生物形成情况、导管留置时间与堵管率等方面是否存在不同.结果 肝素钠组与生理盐水组导管内赘生物情况、导管留置时间差异无显著意义,P>0.05;导管内赘生物情况与导管留置时间呈正相关,r=0.112;两组导管堵管率亦不存在统计学差异,P>0.05.结论 生理盐水冲封管对导管内赘生物情况、导管堵管率等可以起到与肝素钠溶液冲封管相同的效果,且生理盐水符合人体内环境,对血管刺激小,操作简单方便,提高了护理工作的安全性、有效性.%Objective To study the effects of the two different tube-sealing fluids in the formation of tube excrescence and tube-plugging. Method 126 stomach cancer patients with central venous catheter were randomly divided into heparin group and sodium group. For the heparin group, 6~8 ml heparin sodium (50 U/ml) was adopted for sealing trochar, and for the sodium group, 6~8 ml 0. 9% normal saline was adopted for sealing trochar. The difference of tube excrescence and tube-plugging was compared. Result There were no differences in the formation of tube excrescence and the indwelling time between the heparin group and the sodium group(P>0.05). There was positive correlation between the formation of tube excrescence and the indwelling time. And there was no difference in tube-plugging between the two groups(P>0. 05). Conclusion 0. 9% normal saline can achieve the effects of heparin sodium in the formation of tube excrescence and tube-plugging. so the normal saline can replace heparin sodium because of its low price and

  18. Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), Prevents Platelet Activation in Human Platelets. (United States)

    Lee, Ye-Ming; Hsieh, Kuo-Hsien; Lu, Wan-Jung; Chou, Hsiu-Chu; Chou, Duen-Suey; Lien, Li-Ming; Sheu, Joen-Rong; Lin, Kuan-Hung


    Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus lupulus L.). Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited platelet activation accompanied by relative [Ca(2+)](i) mobilization, thromboxane A(2) formation, hydroxyl radical (OH(●)) formation, and phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ, an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory effect on platelet aggregation. Furthermore, xanthohumol did not significantly increase nitrate formation in platelets. This study demonstrates for the first time that xanthohumol possesses potent antiplatelet activity which may initially inhibit the PI3-kinase/Akt, p38 MAPK, and PLCγ2-PKC cascades, followed by inhibition of the thromboxane A(2) formation, thereby leading to inhibition of [Ca(2+)](i) and finally inhibition of platelet aggregation. Therefore, this novel role of xanthohumol may represent a high therapeutic potential for treatment or prevention of cardiovascular diseases.

  19. Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus, Prevents Platelet Activation in Human Platelets

    Directory of Open Access Journals (Sweden)

    Ye-Ming Lee


    Full Text Available Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus lupulus L.. Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited platelet activation accompanied by relative [Ca2+]i mobilization, thromboxane A2 formation, hydroxyl radical (OH● formation, and phospholipase C (PLCγ2, protein kinase C (PKC, mitogen-activated protein kinase (MAPK, and Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ, an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory effect on platelet aggregation. Furthermore, xanthohumol did not significantly increase nitrate formation in platelets. This study demonstrates for the first time that xanthohumol possesses potent antiplatelet activity which may initially inhibit the PI3-kinase/Akt, p38 MAPK, and PLCγ2-PKC cascades, followed by inhibition of the thromboxane A2 formation, thereby leading to inhibition of [Ca2+]i and finally inhibition of platelet aggregation. Therefore, this novel role of xanthohumol may represent a high therapeutic potential for treatment or prevention of cardiovascular diseases.

  20. Haemostatic role of intermediate filaments in adhered platelets: importance of the membranous system stability. (United States)

    Cerecedo, Doris; Martínez-Vieyra, Ivette; Mondragón, Ricardo; Mondragón, Mónica; González, Sirenia; Galván, Iván J


    The role of platelets in coagulation and the haemostatic process was initially suggested two centuries ago, and under appropriate physiological stimuli, these undergo abrupt morphological changes, attaching and spreading on damaged endothelium, preventing bleeding. During the adhesion process, platelet cytoskeleton reorganizes generating compartments in which actin filaments, microtubules, and associated proteins are arranged in characteristic patterns mediating crucial events, such as centralization of their organelles, secretion of granule contents, aggregation with one another to form a haemostatic plug, and retraction of these aggregates. However, the role of Intermediate filaments during the platelet adhesion process has not been explored. J. Cell. Biochem. 114: 2050-2060, 2013. © 2013 Wiley Periodicals, Inc.

  1. Modular, Plug and Play, Distributed Avionics Project (United States)

    National Aeronautics and Space Administration — The objective of this SBIR effort was to prove the viability of an Ethernet version of the MicroSat Systems, Inc. (MSI) modular, plug and play (PnP) spacecraft...

  2. Bone Formation with Deproteinized Bovine Bone Mineral or Biphasic Calcium Phosphate in the Presence of Autologous Platelet Lysate: Comparative Investigation in Rabbit

    Directory of Open Access Journals (Sweden)

    Carole Chakar


    Full Text Available Bone substitutes alone or supplemented with platelet-derived concentrates are widely used to promote bone regeneration but their potency remains controversial. The aim of this study was, therefore, to compare the regenerative potential of preparations containing autologous platelet lysate (APL and particles of either deproteinized bovine bone mineral (DBBM or biphasic calcium phosphate (BCP, two bone substitutes with different resorption patterns. Rabbit APL was prepared by freeze-thawing a platelet suspension. Critical-size defects in rabbit femoral condyle were filled with DBBM or DBBM+APL and BCP or BCP+APL. Rabbits were sacrificed after six weeks and newly formed bone and residual implanted material were evaluated using nondemineralized histology and histomorphometry. New bone was observed around particles of all fillers tested. In the defects filled with BCP, the newly formed bone area was greater (70%; P<0.001 while the residual material area was lower (60%; P<0.001 than that observed in those filled with DBBM. New bone and residual material area of defects filled with either APL+DBBM or APL+BCP were similar to those observed in those filled with the material alone. In summary, osteoconductivity and resorption of BCP were greater than those of DBBM, while APL associated with either DBBM or BCP did not have an additional benefit.


    Energy Technology Data Exchange (ETDEWEB)

    M.A. Ebadian, Ph.D.


    This project, which began in FY97, involves both the flow loop research on plugging and unplugging of waste transfer pipelines, and the large-scale industrial equipment test of plugging locating and unplugging technologies. In FY98, the related work was performed under the project name ''Mixing, Settling, and Pipe Unplugging of Waste Transfer Lines.'' The mixing, settling, and pipeline plugging and unplugging are critical to the design and maintenance of a waste transfer pipeline system, especially for the High-Level Waste (HLW) pipeline transfer. The major objective of this work is to recreate pipeline plugging conditions for equipment testing of plug locating and removal and to provide systematic operating data for modification of equipment design and enhancement of performance of waste transfer lines used at DOE sites. As the waste tank clean-out and decommissioning program becomes active at the DOE sites, there is an increasing potential that the waste slurry transfer lines will become plugged and unable to transport waste slurry from one tank to another or from the mixing tank to processing facilities. Transfer systems may potentially become plugged if the solids concentration of the material being transferred increases beyond the capability of the prime mover or if upstream mixing is inadequately performed. Plugging can occur due to the solids' settling in either the mixing tank, the pumping system, or the transfer lines. In order to enhance and optimize the slurry's removal and transfer, refined and reliable data on the mixing, sampling, and pipe unplugging systems must be obtained based on both laboratory-scale and simulated in-situ operating conditions.

  4. Hybrid and Plug-in Electric Vehicles

    Energy Technology Data Exchange (ETDEWEB)



    Hybrid and plug-in electric vehicles use electricity either as their primary fuel or to improve the efficiency of conventional vehicle designs. This new generation of vehicles, often called electric drive vehicles, can be divided into three categories: hybrid electric vehicles (HEVs), plug-in hybrid electric vehicles(PHEVs), and all-electric vehicles (EVs). Together, they have great potential to reduce U.S. petroleum use.

  5. The thermodynamics and kinetics of phosphoester bond formation, use, and dissociation in biology, with the example of polyphosphate in platelet activation, trasience, and mineralization. (United States)

    Omelon, S. J.


    Mitochondria condense orthophosphates (Pi), forming phosphoester bonds for ATP production that is important to life. This represents an exchange of energy from dissociated carbohydrate bonds to phosophoester bonds. These bonds are available to phosphorylate organic compounds or hydrolyze to Pi, driving many biochemical processes. The benthic bacteria T. namibiensis 1 and Beggiatoa 2 condense Pi into phosphate polymers in oxygenated environments. These polyphosphates (polyPs) are stored until the environment becomes anoxic, when these bacteria retrieve the energy from polyP dissociation into Pi3. Dissociated Pi is released outside of the bacteria, where it precipitates as apatite.The Gibbs free energy of polyP phosphoester bond hydrolysis is negative, however, the kinetics are slow4. Diatoms contain a polyP pool that is stable until after death, after which the polyPs hydrolyze and form apatite5. The roles of polyP in eukaryotic organism biochemistry continue to be discovered. PolyPs have a range of biochemical roles, such as bioavailable P-storage, stress adaptation, and blood clotting6. PolyP-containing granules are released from anuclear platelets to activate factor V7 and factor XII in the blood clotting process due to their polyanionic charge8. Platelets have a lifespan of approximately 8 days, after which they undergo apoptosis9. Data will be presented that demonstrate the bioactive, thermodynamically unstable polyP pool within older platelets in vitro can spontaneously hydrolyze and form phosphate minerals. This process is likely avoided by platelet digestion in the spleen and liver, possibly recycling platelet polyPs with their phosphoester bond energy for other biochemical roles. 1 Schulz HN et al. Science (2005) 307: 416-4182 Brüchert V et al. Geochim Cosmochim Acta (2003) 67: 4505-45183 Goldhammer T et al. Nat Geosci (2010) 3: 557-5614 de Jager H-J et al. J Phys Chem A (1988) 102: 2838-28415 Diaz, J et al. Science (2008) 320: 652-6556 Mason KD et al

  6. Mice lacking the SLAM family member CD84 display unaltered platelet function in hemostasis and thrombosis.

    Directory of Open Access Journals (Sweden)

    Sebastian Hofmann

    Full Text Available 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.

  7. Study of borehole plugging in bedded salt domes by earth melting technology

    Energy Technology Data Exchange (ETDEWEB)

    Black, D.L.


    The intent of this program is to define the most viable Melted In situ Rock salt Plug (MIRP) System options, these options being addressed primarily from the downhole subsystem perspective, with a conventional drill rig as the basis for the surface part of the MIRP System. Preliminary experiments had indicated that it is possible to backfill the open penetrations in the domed salt deposits with a melted in situ rocksalt plug such that in time the melted rock salt plug effectively duplicates the parent virgin salt. The programmatic assumption for the requirement of duplicating the virgin salt with a MIRP provides the basis for this study. A system functional analysis was performed to establish the requirements for the performance of the overall MIRP System. A similar functional analysis was conducted for the salt plug that would be formed by the MIRP System. Based on the analyses of the material, thermal, and structural behavior of the salt plug, the requirements for the formation of an acceptable salt plug were determined. From the functional analysis a determination was made of the operation of the hardware for the downhole portion of the MIRP System. From that perspective several design concepts were formulated. For these design concepts a technology roadmap was developed. The pertinent aspects, results, conclusions and recommendations of the above are summarized in the sections that follow.

  8. Detection of Membrane Fluidity in Submitochondrial Particles of Platelets and Erythrocyte Membranes from Mexican Patients with Alzheimer Disease by Intramolecular Excimer Formation of 1,3 Dipyrenylpropane

    Directory of Open Access Journals (Sweden)

    G.G. Ortiz


    Full Text Available It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged-matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes.

  9. Underwater connect and disconnect plug and receptacle (United States)

    Dodier, Paul J.


    A plug and receptacle combination is transformer coupled. There are no exposed contacts to the environment at any time, whether the plug and receptacle combination are mated or separated from each other. By encapsulating the primary winding and secondary winding separately in a respective plug and receptacle, mating and unmating can be accomplished while submerged in water. The inventive device is useful in any underwater activity in which a diver must attach a power cable to a power driven tool, light, pump, etc., while submerged. In addition submarines could have the receptacles installed outboard of the pressure hull to be used in the event it became disabled at a depth attainable by a diver. A diver could descend with cables and plug them into the receptacles providing power and communications to the stranded crew awaiting rescue. The inventions could also be used in the home as a safety device where no voltage would be exposed. Either the plug or the receptacle shown could be built into the wall. Whichever items is built into the wall would receive the power source and have the primary winding.

  10. Erosion on spark plug electrodes; Funkenerosion an Zuendkerzenelektroden

    Energy Technology Data Exchange (ETDEWEB)

    Rager, J.


    Durability of spark plugs is mainly determined by spark gap widening, caused by electrode wear. Knowledge about the erosion mechanisms of spark plug materials is of fundamental interest for the development of materials with a high resistance against electrode erosion. It is therefore crucial to identify those parameters which significantly influence the erosion behaviour of a material. In this work, a reliable and reproducible testing method is presented which produces and characterizes electrode wear under well-defined conditions and which is capable of altering parameters specifically. Endurance tests were carried out to study the dependence of the wear behaviour of pure nickel and platinum on the electrode temperature, gas, electrode gap, electrode diameter, atmospheric pressure, and partial pressure of oxygen. It was shown that erosion under nitrogen is negligible, irrespective of the material. This disproves all common mechanism discussed in the literature explaining material loss of spark plug electrodes. Based on this observation and the variation of the mentioned parameters a new erosion model was deduced. This relies on an oxidation of the electrode material and describes the erosion of nickel and platinum separately. For nickel, electrode wear is caused by the removal of an oxide layer by the spark. In the case of platinum, material loss occurs due to the plasma-assisted formation and subsequent evaporation of volatile oxides in the cathode spot. On the basis of this mechanism a new composite material was developed whose erosion resistance is superior to pure platinum. Oxidation resistant metal oxide particles were added to a platinum matrix, thus leading to a higher erosion resistance of the composite. However, this can be decreased by a side reaction, the separation of oxygen from the metal oxides, which effectively assists the oxidation of the matrix. This reaction can be suppressed by using highly stable oxides, characterized by a large negative Gibbs

  11. Regulation of the genetic code in megakaryocytes and platelets. (United States)

    Rondina, M T; Weyrich, A S


    Platelets are generated from nucleated precursors referred to as megakaryocytes. The formation of platelets is one of the most elegant and unique developmental processes in eukaryotes. Because they enter the circulation without nuclei, platelets are often considered simple, non-complex cells that have limited functions beyond halting blood flow. However, emerging evidence over the past decade demonstrates that platelets are more sophisticated than previously considered. Platelets carry a rich repertoire of messenger RNAs (mRNAs), microRNAs (miRNAs), and proteins that contribute to primary (adhesion, aggregation, secretion) and alternative (immune regulation, RNA transfer, translation) functions. It is also becoming increasingly clear that the 'genetic code' of platelets changes with race, genetic disorders, or disease. Changes in the 'genetic code' can occur at multiple points including megakaryocyte development, platelet formation, or in circulating platelets. This review focuses on regulation of the 'genetic code' in megakaryocytes and platelets and its potential contribution to health and disease. © 2015 International Society on Thrombosis and Haemostasis.

  12. Platelet reactions to modified surfaces under dynamic conditions. (United States)

    Rhodes, N P; Shortland, A P; Rattray, A; Williams, D F


    The influence of surfaces on the reactions of platelets in whole blood under laminar flow was investigated in a cone and plate viscometer. Citrated whole blood was exposed to steel, PMMA and PMMA modified with PEO at low (500 s(-1)) and high (4000 s(-1)) wall shear rates at room temperature for a period of 100 s. Treated blood samples were fixed with paraformaldehyde, stained with a monoclonal antibody for CD41 (platelet GPIIb/IIIa) conjugated with phycoerythrin and analyzed by flow cytometry. The reactions of platelets (microparticle generation and formation of platelet-platelet, platelet-red blood cell and red blood cell-microparticle aggregates) to these environments were quantified. Additionally, the size of platelet-platelet aggregates was assessed. The percentage platelet aggregation and numbers of microparticles generated were independent of surface type at any shear rate. The composition of the aggregates formed was influenced by the surface: at low and high shear rates PMMA caused the generation of platelet-platelet aggregates of the greatest size. The numbers of red blood cell-platelet and red blood cell-microparticle aggregates also varied depending on the surface. Fewer red blood cell-platelet aggregates were formed at higher shear rates, whereas the reverse was true for red blood cell-microparticle aggregates. It is concluded that these variations may help to explain the differential effects of surfaces to the induction of distant thrombotic events: microparticles may be protected from loss from the blood stream by their association with red blood cells at high shear rates.

  13. Plug-in hybrid electric vehicle R&D plan

    Energy Technology Data Exchange (ETDEWEB)

    None, None


    FCVT, in consultation with industry and other appropriate DOE offices, developed the Draft Plug-In Hybrid Electric Vehicle R&D Plan to accelerate the development and deployment of technologies critical for plug-in hybrid vehicles.

  14. Jet noise suppression by porous plug nozzles (United States)

    Bauer, A. B.; Kibens, V.; Wlezien, R. W.


    Jet noise suppression data presented earlier by Maestrello for porous plug nozzles were supplemented by the testing of a family of nozzles having an equivalent throat diameter of 11.77 cm. Two circular reference nozzles and eight plug nozzles having radius ratios of either 0.53 or 0.80 were tested at total pressure ratios of 1.60 to 4.00. Data were taken both with and without a forward motion or coannular flow jet, and some tests were made with a heated jet. Jet thrust was measured. The data were analyzed to show the effects of suppressor geometry on nozzle propulsive efficiency and jet noise. Aerodynamic testing of the nozzles was carried out in order to study the physical features that lead to the noise suppression. The aerodynamic flow phenomena were examined by the use of high speed shadowgraph cinematography, still shadowgraphs, extensive static pressure probe measurements, and two component laser Doppler velocimeter studies. The different measurement techniques correlated well with each other and demonstrated that the porous plug changes the shock cell structure of a standard nozzle into a series of smaller, periodic cell structures without strong shock waves. These structures become smaller in dimension and have reduced pressure variations as either the plug diameter or the porosity is increased, changes that also reduce the jet noise and decrease thrust efficiency.

  15. Mass transport through defected bentonite plugs

    Energy Technology Data Exchange (ETDEWEB)

    Oscarson, D.W.; Dixon, D.A.; Hume, H.B


    Compacted bentonite-based materials are important barriers in many waste containment strategies. To function as effective barriers, however, these materials must maintain their low water permeability and molecular diffusivity for long periods of time under a variety of environmental conditions. Here we examine the permeability and diffusivity of compacted bentonite plugs that were either slotted, to mimic fractures, parallel to the direction of mass flow or heated at 150 and 250{sup o}C for several weeks at various moisture contents before testing. The dry density of the plugs ranged from about 0.9 to 1.3 Mg/m{sup 3}. The results show that the saturated hydraulic conductivity and diffusivity (for I{sup -} and Cs{sup +}) of the treated or 'defected' bentonite plugs are essentially the same as those of untreated plugs at similar densities. This provides confidence that compacted bentonitic materials can function effectively as barriers for long periods of time under a range of environmental conditions. (author)

  16. Feasibility of Upper Port Plug tube handling

    NARCIS (Netherlands)

    Koning, J.F.; Elzendoorn, B.S.Q.; Ronden, D.M.S.; Klinkhamer, J.F.F.; Biel, W.; Krasikov, Y.; Walker, C.I.


    Central, retractable tubes are proposed in several Upper Port Plugs (UPPs) designs for ITER, to enable fast exchange of specific components of diagnostics housed in these UPPs. This paper investigates into possible designs to enable the efficient handling of tubes. The feasibility of tube handling i

  17. Numerical Analysis of Soil Plug Inside Suction Foundations During Suction Penetration by Discrete Element Method

    Institute of Scientific and Technical Information of China (English)


    The phenomenon of the soil plug usually rising inside the suction foundations during suction penetration was quantitatively described and predicted. The formation process of the soil plug was simulated and calculated by DEM (discrete element method) model. The seepage flow, the self-weight of soil, the friction on the chamber wall as well as the suction inside the chamber are considered as the main external forces in the process. The results are compared with a set of laboratory model tests performed by using three soil types (sand, silty clay and clay) in the Bohai Sea area. The heights of soil plug from numerical estimations are lower than those from model test results, mainly because the suction pressure and friction resistance are applied in an ideal way under the numerical simulation.

  18. Performance of direct injection methanol engine using the fuel jet impingement and diffusion. ; Comparison between the spark plug and glow plug ignitions. Nenryo funryu no shototsu kakusan wo riyoshita chokufun methanol kikan no seino. ; Spark plug oyobi glow plug chakka hoshiki no hikaku

    Energy Technology Data Exchange (ETDEWEB)

    Kato, S.; Onishi, S.


    The purpose of this paper is to compare the performance of direct fuel injection methanol engines with the spark plug and glow plug ignition systems. These methanol engines utilize the formation of fuel-air mixture by the fuel jet impingement and diffusion. Engine performance and cylinder pressure for the both ignition systems were analyzed. Piezoelectric pressure indicator was used for the cylinder pressure measurements, and combustion analyzer was used for their analyses. In order to estimate engine performance, effects of load and engine speed were analyzed. Consequently, almost the same brake thermal efficiencies (maximum value of 42%) were obtained for both ignition systems. For the glow plug ignition system, the combustion noise and NOx emission were lower than the spark plug engine. The NOx emission did not excess 500ppm with the glow plug ignition system. In the impingement and diffusion method, both the piston attached type impingement part and cylinder head fixed type one were applicable. 4 refs., 9 figs., 2 tabs.

  19. Platelet alloimmunization after transfusion

    DEFF Research Database (Denmark)

    Taaning, E; Simonsen, A C; Hjelms, E;


    BACKGROUND AND OBJECTIVES: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. MATERIALS AND METHODS: We studied the frequency of alloimmunization against platelet antigens in 117 patient...

  20. Platelet activation and aggregation

    DEFF Research Database (Denmark)

    Jensen, Maria Sander; Larsen, O H; Christiansen, Kirsten


    This study introduces a new laboratory model of whole blood platelet aggregation stimulated by endogenously generated thrombin, and explores this aspect in haemophilia A in which impaired thrombin generation is a major hallmark. The method was established to measure platelet aggregation initiated...

  1. Gasotransmitters and platelets. (United States)

    Truss, Nicola J; Warner, Timothy D


    Platelets are essential to prevent blood loss and promote wound healing. Their activation comprises of several complex steps which are regulated by a range of mediators. Over the last few decades there has been intense interest in a group of gaseous mediators known as gasotransmitters; currently comprising nitric oxide (NO), carbon monoxide (CO) and hydrogen sulphide (H(2)S). Here we consider the action of gasotransmitters on platelet activity. NO is a well established platelet inhibitor which mediates its effects predominantly through activation of soluble guanylyl cyclase leading to a decrease in intraplatelet calcium. More recently CO has been identified as a gasotransmitter with inhibitory actions on platelets; CO acts through the same mechanism as NO but is less potent. The in vivo and platelet functions of the most recently identified gasotransmitter, H(2)S, are still the subject of investigations, but they appear generally inhibitory. Whilst there is evidence for the individual action of these mediators, it is also likely that combinations of these mediators are more relevant regulators of platelets. Furthermore, current evidence suggests that these mediators in combination alter the production of each other, and so modify the circulating levels of gasotransmitters. The use of gasotransmitters as therapeutic agents is also being explored for a range of indications. In conclusion, the importance of NO in the regulation of vascular tone and platelet activity has long been understood. Other gasotransmitters are now establishing themselves as mediators of vascular tone, and recent evidence suggests that these other gasotransmitters may also modulate platelet function.

  2. Monocyte-Platelet Interaction Induces a Pro-Inflammatory Phenotype in Circulating Monocytes



    BACKGROUND: Activated platelets exert a pro-inflammatory action that can be largely ascribed to their ability to interact with leukocytes and modulate their activity. We hypothesized that platelet activation and consequent formation of monocyte-platelet aggregates (MPA) induces a pro-inflammatory phenotype in circulating monocytes. METHODOLOGY/PRINCIPAL FINDINGS: CD62P(+) platelets and MPA were measured, and monocytes characterized, by whole blood flow cytometry in healthy subjects, before an...

  3. Influence of Cardiopulmonary Bypass on the Interaction of Recombinant Factor VIIa with Activated Platelets


    Kjalke, Marianne; Runge, Marx; Rojkjaer, Rasmus; Steinbruchel, Daniel; Johansson, Pär I


    Recombinant factor VIIa (rFVIIa) interacts preferentially with coated platelets characterized by a high exposure of phosphatidyl serine (PS), FV, FVIII, FIX, and FX binding, and fibrinogen. Cardiopulmonary bypass (CPB) is known to impair platelet function. In this study, the influence of CPB on formation of coated platelets and the interaction of rFVIIa with the platelets were studied. Blood was either exposed to a closed CPB circuit or obtained from patients undergoing CPB-assisted cardiac s...

  4. Detection of Platelet-Monocyte Aggregates by the ADAM® Image Cytometer


    Jung, Bo Kyeung; Cho, Chi Hyun; Moon, Kyung Chul; sung Hur, Dae; YOON, Jeong-Ah; Yoon, Soo-Young


    Background: Inappropriate platelet activation is known to be associated with various thrombotic disorders. Platelet-monocyte aggregates (PMAs), whose formation is mediated by platelet surface P-selectin (CD62P), can be used as a reliable marker to detect platelet activation. Previous studies have generally detected PMAs through flow cytometry-based approaches. Recently, the ADAM® image cytometer (Nanoentek Inc., Seoul, Korea) was developed for image-based cellular analysis. In this study, we ...

  5. Bond strength of cementitious borehole plugs in welded tuff

    Energy Technology Data Exchange (ETDEWEB)

    Akgun, H.; Daemen, J.J.K. [Arizona Univ., Tucson, AZ (USA). Dept. of Mining and Geological Engineering


    Axial loads on plugs or seals in an underground repository due to gas, water pressures and temperature changes induced subsequent to waste and plug emplacement lead to shear stresses at the plug/rock contact. Therefore, the bond between the plug and rock is a critical element for the design and effectiveness of plugs in boreholes, shafts or tunnels. This study includes a systematic investigation of the bond strength of cementitious borehole plugs in welded tuff. Analytical and numerical analysis of borehole plug-rock stress transfer mechanics is performed. The interface strength and deformation are studied as a function of Young`s modulus ratio of plug and rock, plug length and rock cylinder outside-to-inside radius ratio. The tensile stresses in and near an axially loaded plug are analyzed. The frictional interface strength of an axially loaded borehole plug, the effect of axial stress and lateral external stress, and thermal effects are also analyzed. Implications for plug design are discussed. The main conclusion is a strong recommendation to design friction plugs in shafts, drifts, tunnels or boreholes with a minimum length to diameter ratio of four. Such a geometrical design will reduce tensile stresses in the plug and in the host rock to a level which should minimize the risk of long-term deterioration caused by excessive tensile stresses. Push-out tests have been used to determine the bond strength by applying an axial load to cement plugs emplaced in boreholes in welded tuff cylinders. A total of 130 push-out tests have been performed as a function of borehole size, plug length, temperature, and degree of saturation of the host tuff. The use of four different borehole radii enables evaluation of size effects. 119 refs., 42 figs., 20 tabs.

  6. An optimal design for millimeter-wide facture plugging zone

    Directory of Open Access Journals (Sweden)

    Yili Kang


    Full Text Available Lost circulation control in millimeter-wide fractures has been a challenge in well drilling all the time. Low pressure-bearing capacity of a plugging zone will result in excessive consumption of lost circulation materials (LCMs and extra down time. In this study, laboratory experiments were conducted on the plugging of millimeter-wide fractures to evaluate the plugging effects of different types of LCM including rigid granules, elastic particles and fiber. Maximum plugging pressure, total loss volume before sealing and plugging time were taken as the evaluation index of the LCM plugging effect. According to the experimental results, the synergistic plugging mechanisms of different LCM combinations were also analyzed. Experimental results showed that the total loss volume of the plugging zone formed by rigid and elastic particle combination was generally greater than 400 mL, and the maximum plugging pressure of the plugging zone formed by elastic particle and fiber combination was generally less than 6 MPa. In contrast, the plugging zone formed by the combination of the three types of LCMs has the maximum plugging pressure of up to 13 MPa and total loss volume before sealing of 75 mL. In the synergistic plugging process, rigid granules form a frame with high pressure-bearing capacity in the narrower parts of the fractures; elastic particles generate elastic force through elastic deformation to increase the friction between a fracture and a plugging zone to make the plugging zone more stable; fibers filling in the pore space between the particles increase the tightness and integrity of the plugging zone. The experimental results can provide guidance for the optimal design of LCMs used in the field.

  7. Up-Regulated Expression of Matrix Metalloproteinases in Endothelial Cells Mediates Platelet Microvesicle-Induced Angiogenesis

    Directory of Open Access Journals (Sweden)

    Cheng Sun


    Full Text Available Background/Aims: Platelet microvesicles (PMVs contribute to angiogenesis and vasculogenesis, but the mechanisms underlying these contributions have not been fully elucidated. In the present study, we investigated whether PMVs regulate the angiogenic properties of endothelial cells (ECs via mechanisms extending beyond the transport of angiogenic regulators from platelets. Methods: In vitro Matrigel tube formation assay and in vivo Matrigel plug assay were used to evaluate the pro-angiogenic activity of PMVs. The effects of PMVs on the migration of human umbilical vein endothelial cells (HUVECs were detected by transwell assay and wound-healing assay. Real-time PCR and western blot were conducted to examine mRNA and protein expression of pro-angiogenic factors in HUVECs. Matrix metalloproteinase (MMP activity was assayed by gelatin zymography. Moreover, the effects of specific MMP inhibitors were tested. Results: PMVs promoted HUVEC capillary-like network formation in a dose-dependent manner. Meanwhile, PMVs dose-dependently facilitated HUVEC migration. Levels of MMP-2 and MMP-9 expression and activity were up-regulated in HUVECs stimulated with PMVs. Inhibition of MMPs decreased their pro-angiogenic and pro-migratory effects on HUVECs. Moreover, we confirmed the pro-angiogenic activity of PMVs in vivo in mice with subcutaneous implantation of Matrigel, and demonstrated that blockade of MMPs attenuated PMV-induced angiogenesis. Conclusion: The findings of our study indicate that PMVs promote angiogenesis by up-regulating MMP expression in ECs via mechanism extending beyond the direct delivery of angiogenic factors.

  8. The relationship between fractional flow reserve, platelet reactivity and platelet leukocyte complexes in stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Jan-Willem E M Sels

    Full Text Available BACKGROUND: The presence of stenoses that significantly impair blood flow and cause myocardial ischemia negatively affects prognosis of patients with stable coronary artery disease. Altered platelet reactivity has been associated with impaired prognosis of stable coronary artery disease. Platelets are activated and form complexes with leukocytes in response to microshear gradients caused by friction forces on the arterial wall or flow separation. We hypothesized that the presence of significantly flow-limiting stenoses is associated with altered platelet reactivity and formation of platelet-leukocyte complexes. METHODS: One hundred patients with stable angina were studied. Hemodynamic significance of all coronary stenoses was assessed with Fractional Flow Reserve (FFR. Patients were classified FFR-positive (at least one lesion with FFR≤0.75 or FFR-negative (all lesions FFR>0.80. Whole blood samples were stimulated with increasing concentrations of ADP, TRAP, CRP and Iloprost with substimulatory ADP. Expression of P-selectin as platelet activation marker and platelet-leukocyte complexes were measured by flowcytometry. Patients were stratified on clopidogrel use. FFR positive and negative patient groups were compared on platelet reactivity and platelet-leukocyte complexes. RESULTS: Platelet reactivity between FFR-positive patients and FFR-negative patients did not differ. A significantly lower percentage of circulating platelet-neutrophil complexes in FFR-positive patients and a similar non-significant decrease in percentage of circulating platelet-monocyte complexes in FFR-positive patients was observed. CONCLUSION: The presence of hemodynamically significant coronary stenoses does not alter platelet reactivity but is associated with reduced platelet-neutrophil complexes in peripheral blood of patients with stable coronary artery disease.

  9. Platelet-derived HMGB1 is a critical mediator of thrombosis. (United States)

    Vogel, Sebastian; Bodenstein, Rebecca; Chen, Qiwei; Feil, Susanne; Feil, Robert; Rheinlaender, Johannes; Schäffer, Tilman E; Bohn, Erwin; Frick, Julia-Stefanie; Borst, Oliver; Münzer, Patrick; Walker, Britta; Markel, Justin; Csanyi, Gabor; Pagano, Patrick J; Loughran, Patricia; Jessup, Morgan E; Watkins, Simon C; Bullock, Grant C; Sperry, Jason L; Zuckerbraun, Brian S; Billiar, Timothy R; Lotze, Michael T; Gawaz, Meinrad; Neal, Matthew D


    Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation and acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets in multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 in thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation of HMGB1 and determined that platelet-derived HMGB1 is a critical mediator of thrombosis. Mice lacking HMGB1 in platelets exhibited increased bleeding times as well as reduced thrombus formation, platelet aggregation, inflammation, and organ damage during experimental trauma/hemorrhagic shock. Platelets were the major source of HMGB1 within thrombi. In trauma patients, HMGB1 expression on the surface of circulating platelets was markedly upregulated. Moreover, evaluation of isolated platelets revealed that HMGB1 is critical for regulating platelet activation, granule secretion, adhesion, and spreading. These effects were mediated via TLR4- and MyD88-dependent recruitment of platelet guanylyl cyclase (GC) toward the plasma membrane, followed by MyD88/GC complex formation and activation of the cGMP-dependent protein kinase I (cGKI). Thus, we establish platelet-derived HMGB1 as an important mediator of thrombosis and identify a HMGB1-driven link between MyD88 and GC/cGKI in platelets. Additionally, these findings suggest a potential therapeutic target for patients sustaining trauma and other inflammatory disorders associated with abnormal coagulation.

  10. Alloimmune refractoriness to platelet transfusions. (United States)

    Sandler, S G


    Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

  11. Platelet function in dogs

    DEFF Research Database (Denmark)

    Nielsen, Line A.; Zois, Nora Elisabeth; Pedersen, Henrik D.


    Cairn Terriers, 10 Boxers, and 11 Labrador Retrievers) were included in the study. Platelet function was assessed by whole-blood aggregation with ADP (1, 5, 10, and 20 µM) as agonist and by PFA-100 using collagen and epinephrine (Col + Epi) and Cpæ + ADP as agonists. Plasma thromboxane B2 concentration......Background: Clinical studies investigating platelet function in dogs have had conflicting results that may be caused by normal physiologic variation in platelet response to agonists. Objectives: The objective of this study was to investigate platelet function in clinically healthy dogs of 4...... different breeds by whole-blood aggregometry and with a point-of-care platelet function analyzer (PFA-100), and to evaluate the effect of acetylsalicylic acid (ASA) administration on the results from both methods. Methods: Forty-five clinically healthy dogs (12 Cavalier King Charles Spaniels [CKCS], 12...

  12. Cisplatin triggers platelet activation. (United States)

    Togna, G I; Togna, A R; Franconi, M; Caprino, L


    Clinical observations suggest that anticancer drugs could contribute to the thrombotic complications of malignancy in treated patients. Thrombotic microangiopathy, myocardial infarction, and cerebrovascular thrombotic events have been reported for cisplatin, a drug widely used in the treatment of many solid tumours. The aim of this study is to explore in vitro cisplatin effect on human platelet reactivity in order to define the potentially active role of platelets in the pathogenesis of cisplatin-induced thrombotic complications. Our results demonstrate that cisplatin increases human platelet reactivity (onset of platelet aggregation wave and thromboxane production) to non-aggregating concentrations of the agonists involving arachidonic acid metabolism. Direct or indirect activation of platelet phospholipase A(2) appears to be implicated. This finding contributes to a better understanding of the pathogenesis of thrombotic complications occurring during cisplatin-based chemotherapy.

  13. Platelet function in dogs

    DEFF Research Database (Denmark)

    Nielsen, Line A.; Zois, Nora Elisabeth; Pedersen, Henrik D.


    Background: Clinical studies investigating platelet function in dogs have had conflicting results that may be caused by normal physiologic variation in platelet response to agonists. Objectives: The objective of this study was to investigate platelet function in clinically healthy dogs of 4...... different breeds by whole-blood aggregometry and with a point-of-care platelet function analyzer (PFA-100), and to evaluate the effect of acetylsalicylic acid (ASA) administration on the results from both methods. Methods: Forty-five clinically healthy dogs (12 Cavalier King Charles Spaniels [CKCS], 12...... applied. However, the importance of these breed differences remains to be investigated. The PFA-100 method with Col + Epi as agonists, and ADP-induced platelet aggregation appear to be sensitive to ASA in dogs....

  14. Measurement of platelet aggregation, independently of patient platelet count

    DEFF Research Database (Denmark)

    Vinholt, P. J.; Frederiksen, H.; Hvas, A.M.


    platelet aggregation ruled out bleeding tendency in thrombocytopenic patients. Summary: Background: Methods for testing platelet aggregation in thrombocytopenia are lacking. Objective: To establish a flow-cytometric test of in vitro platelet aggregation independently of the patient's platelet count......, and examine the association of aggregation with a bleeding history in thrombocytopenic patients. Patients/methods: We established a flow-cytometric assay of platelet aggregation, and measured samples from healthy individuals preincubated with antiplatelet drugs, and samples from two patients with inherited...... platelets at platelet counts of > 10 × 109 L-1; otherwise, platelet isolation was required. The platelet aggregation percentage decreased with increasing antiplatelet drug concentration. Platelet aggregation in patients was reduced as compared with healthy individuals: 42% (interquartile range [IQR] 27...

  15. Lyotropic hexagonal columnar liquid crystals of large colloidal gibbsite platelets

    NARCIS (Netherlands)

    Mourad, M.C.D.; Petukhov, A.V.; Vroege, G.J.; Lekkerkerker, H.N.W.


    We report the formation of hexagonal columnar liquid crystal phases in suspensions of large (570 nm diameter), sterically stabilized, colloidal gibbsite platelets in organic solvent. In thin cells these systems display strong iridescence originating from hexagonally arranged columns that are

  16. Platelet-collagen adhesion enhances platelet aggregation induced by binding of VWF to platelets

    Energy Technology Data Exchange (ETDEWEB)

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA) State Univ. of New York, Buffalo (USA))


    Ristocetin-induced platelet aggregation (RIPA) was evaluated in the presence of platelet-collagen adhesion. RIPA of normal donor platelet-rich plasma (PRP) demonstrated a primary wave of aggregation mediated by the binding of von Willebrand factor (VWF) to platelets and a secondary aggregation wave, due to a platelet-release reaction, initiated by VWF-platelet binding and inhibitable by acetylsalicylic acid (ASA). An enhanced RIPA was observed in PRP samples to which collagen had been previously added. These subthreshold concentrations of collagen, which by themselves were insufficient to induce aggregation, caused measurable platelet-collagen adhesion. Subthreshold collagen did not cause microplatelet aggregation, platelet release of ({sup 3}H)serotonin, or alter the dose-responsive binding of {sup 125}I-labeled VWF to platelets, which occurred with increasing ristocetin concentrations. However, ASA inhibition of the platelet release reaction prevented collagen-enhanced RIPA. These results demonstrate that platelet-collagen adhesion altered the platelet-release reaction induced by the binding of VWF to platelets causing a platelet-release reaction at a level of VWF-platelet binding not normally initiating a secondary aggregation. These findings suggest that platelet-collagen adhesion enhances platelet function mediated by VWF.

  17. In vitro model of platelet aggregation in stenotic arteries

    Energy Technology Data Exchange (ETDEWEB)

    Morley, D.; Santamore, W.P.


    Clinical and experimental evidence suggest a strong relationship between arterial stenosis, platelet aggregation, and subsequent thrombus formation. To facilitate the study of platelet accumulation in stenotic arteries, we developed an in vitro preparation. Arterial segments were perfused with whole citrated blood. A stenosis was created by applying an external plastic constrictor to the artery. Platelet accumulation within the stenosis was assessed by scanning electron microscopy and by radioactive counts from Indium-111 labeled platelets. Utilizing this preparation, 30 carotid arterial segments from 10 mongrel dogs were perfused at 100 mmHg for 15 min. In 10 arteries without a stenosis, scanning electron microscopy and radioactive counts demonstrated little platelet accumulation. In contrast, extensive platelet aggregation was observed in 10 arteries with stenoses. Moreover, in 10 stenotic arteries exposed to the thromboxane mimetic, U46619 (Upjohn Diagnostic Group), scanning electron microscopy and radioactive counts demonstrated a significant increase in platelet deposition. Conversely, we demonstrated a dimunition of platelet accumulation in stenosed arterial segments exposed to the prostacyclin analogue platelet inhibitor, Iloprost. The in vitro preparation allows precise control of hemodynamic variables and makes it possible to perform multiple tests on segments of the same vessel from the same animal.

  18. Generation of functional platelets from canine induced pluripotent stem cells. (United States)

    Nishimura, Toshiya; Hatoya, Shingo; Kanegi, Ryoji; Sugiura, Kikuya; Wijewardana, Viskam; Kuwamura, Mitsuru; Tanaka, Miyuu; Yamate, Jyoji; Izawa, Takeshi; Takahashi, Masahiro; Kawate, Noritoshi; Tamada, Hiromichi; Imai, Hiroshi; Inaba, Toshio


    Thrombocytopenia (TTP) is a blood disease common to canines and human beings. Currently, there is no valid therapy for this disease except blood transfusion. In this study, we report the generation of canine induced pluripotent stem cells (ciPSCs) from canine embryonic fibroblasts, and a novel protocol for creating mature megakaryocytes (MKs) and functional platelets from ciPSCs. The ciPSCs were generated using lentiviral vectors, and differentiated into MKs and platelets on OP9 stromal cells supplemented with growth factors. Our ciPSCs presented in a tightly domed shape and showed expression of a critical pluripotency marker, REX1, and normal karyotype. Additionally, ciPSCs differentiated into cells derived from three germ layers via the formation of an embryoid body. The MKs derived from ciPSCs had hyperploidy and transformed into proplatelets. The proplatelets released platelets early on that expressed specific MK and platelet marker CD41/61. Interestingly, these platelets, when activated with adenosine diphosphate or thrombin, bind to fibrinogen. Moreover, electron microscopy showed that the platelets had the same ultrastructure as peripheral platelets. Thus, we have demonstrated for the first time the generation of ciPSCs that are capable of differentiating into MKs and release functional platelets in vitro. Our system for differentiating ciPSCs into MKs and platelets promises a critical therapy for canine TTP and appears to be extensible in principle to resolve human TTP.

  19. Stimulation of Platelet Death by Vancomycin

    Directory of Open Access Journals (Sweden)

    Syeda T. Towhid


    Full Text Available Background/Aims: Side effects of vancomycin, a widely used antibiotic, include thrombocytopenia. The vancomycin-induced thrombocytopenia has been attributed to immune reactions. At least in theory, thrombocytopenia could result in part from the triggering of apoptosis, which results in cell shrinkage and cell membrane scrambling with subsequent phosphatidylserine exposure at the cell surface. The cell membrane scrambling could be initiated by a signaling involving increase of cytosolic Ca2+ activity, ceramide formation, mitochondrial depolarization and/or caspase activation. Vancomycin has indeed been shown to trigger neutrophil apoptosis. An effect of vancomycin on platelet apoptosis has, however, never been tested. The present study thus explored the effect of vancomycin on platelet activation and apoptosis. Methods: Human blood platelets were exposed to vancomycin and forward scatter was utilized to estimate cell volume, annexin V-binding to quantify phosphatidylserine (PS exposure, Fluo-3 AM fluorescence to estimate cytosolic Ca2+ activity ([Ca2+]i, antibodies to quantify ceramide formation and immunofluorescence to quantify protein abundance of active caspase-3. Results: A 30 minutes exposure to vancomycin (≥1 µg/ ml decreased cell volume, triggered annexin V-binding, increased [Ca2+]i, activated caspase 3, stimulated ceramide formation, triggered release of thromboxane B2, and upregulated surface expression of CD62P (P-selectin as well as activated integrin αllbβ3. Annexin V-binding and upregulation of CD62P (P-selectin and integrin αllbβ3 was significantly blunted by removal of extracellular Ca2+. Annexin V-binding was not significantly blunted by pan-caspase inhibitor zVAD-FMK (1 µM. In conclusion, vancomycin results in platelet activation and suicidal platelet death with increase of [Ca2+]i, caspase-3 activation, cell membrane scrambling and cell shrinkage. Activation and cell membrane scrambling required the presence of Ca2

  20. Possible roles of platelet-derived microparticles in atherosclerosis. (United States)

    Wang, Zhi-Ting; Wang, Zi; Hu, Yan-Wei


    Platelets and platelet-derived microparticles (PMPs) play important roles in cardiovascular diseases, especially atherosclerosis. Continued research has revealed that PMPs have numerous functions in atherosclerosis, not only in thrombosis formation, but also by induction of inflammation. PMPs also induce formation of foam cells. Recent evidence strongly indicates a significant role of PMPs in atherosclerosis. Here, current research on the function of PMPs in atherosclerosis is reviewed.

  1. Unified theory on the pathogenesis of Randall's plaques and plugs. (United States)

    Khan, Saeed R; Canales, Benjamin K


    Kidney stones develop attached to sub-epithelial plaques of calcium phosphate (CaP) crystals (termed Randall's plaque) and/or form as a result of occlusion of the openings of the Ducts of Bellini by stone-forming crystals (Randall's plugs). These plaques and plugs eventually extrude into the urinary space, acting as a nidus for crystal overgrowth and stone formation. To better understand these regulatory mechanisms and the pathophysiology of idiopathic calcium stone disease, this review provides in-depth descriptions of the morphology and potential origins of these plaques and plugs, summarizes existing animal models of renal papillary interstitial deposits, and describes factors that are believed to regulate plaque formation and calcium overgrowth. Based on evidence provided within this review and from the vascular calcification literature, we propose a "unified" theory of plaque formation-one similar to pathological biomineralization observed elsewhere in the body. Abnormal urinary conditions (hypercalciuria, hyperoxaluria, and hypocitraturia), renal stress or trauma, and perhaps even the normal aging process lead to transformation of renal epithelial cells into an osteoblastic phenotype. With this de-differentiation comes an increased production of bone-specific proteins (i.e., osteopontin), a reduction in crystallization inhibitors (such as fetuin and matrix Gla protein), and creation of matrix vesicles, which support nucleation of CaP crystals. These small deposits promote aggregation and calcification of surrounding collagen. Mineralization continues by calcification of membranous cellular degradation products and other fibers until the plaque reaches the papillary epithelium. Through the activity of matrix metalloproteinases or perhaps by brute physical force produced by the large sub-epithelial crystalline mass, the surface is breached and further stone growth occurs by organic matrix-associated nucleation of CaOx or by the transformation of the outer layer

  2. Revitalization of traumatized immature tooth with platelet-rich fibrin

    Directory of Open Access Journals (Sweden)

    Umrana Faizuddin


    Full Text Available Endodontic treatment options for immature, nonvital teeth conventionally include surgical endodontics, apexification with calcium hydroxide, or single visit mineral trioxide aggregate plug. Regeneration is a new concept which is been introduced in the treatment of traumatized open apex tooth. Regeneration of pulp-dentin complex in an infected necrotic tooth with an open apex is possible if the canal is effectively disinfected. The purpose of this case report is to add a new vista in regenerative, endodontic therapy by using platelet-rich fibrin for revitalization of immature nonvital tooth.

  3. Revitalization of traumatized immature tooth with platelet-rich fibrin (United States)

    Faizuddin, Umrana; Solomon, Raji Viola; Mattapathi, Jayadev; Guniganti, Sushma Shravani


    Endodontic treatment options for immature, nonvital teeth conventionally include surgical endodontics, apexification with calcium hydroxide, or single visit mineral trioxide aggregate plug. Regeneration is a new concept which is been introduced in the treatment of traumatized open apex tooth. Regeneration of pulp-dentin complex in an infected necrotic tooth with an open apex is possible if the canal is effectively disinfected. The purpose of this case report is to add a new vista in regenerative, endodontic therapy by using platelet-rich fibrin for revitalization of immature nonvital tooth. PMID:26681870

  4. In situ formation of CA[sub 6] platelets in Al[sub 2]O[sub 3] and Al[sub 2]O[sub 3]/ZrO[sub 2] matrices

    Energy Technology Data Exchange (ETDEWEB)

    Belmonte, M. (Inst. de Ceramica y Vidrio (CSIC), Madrid (Spain)); Sanchez-Herencia, A.J. (Inst. de Ceramica y Vidrio (CSIC), Madrid (Spain)); Moreno, R. (Inst. de Ceramica y Vidrio (CSIC), Madrid (Spain)); Miranzo, P. (Inst. de Ceramica y Vidrio (CSIC), Madrid (Spain)); Moya, J.S. (Inst. de Ceramica y Vidrio (CSIC), Madrid (Spain)); Tomsia, A.P. (Inst. de Ceramica y Vidrio (CSIC), Madrid (Spain) Lawrence Berkeley Lab. and U.C. Berkeley, CA (United States))


    Al[sub 2]O[sub 3] and Al[sub 2]O[sub 3]/ZrO[sub 2] compacts containing CaO as a dopant have been sintered under different conditions and atmospheres: air, high vacuum (> 10[sup -6]torr). SEM observations have been made on the polished surfaces of sintered and also of annealed samples. Only after the annealing treatment in air at temperatures ranging from 1400 to 1500 C, a massive formation of CA[sub 6] platelets was detected in samples sintered in low oxygen partial pressure atmospheres. In order to clarify the mechanism of formation of this secondary phase at the grain boundaries, CaO has been introduced in the form of either plaster of Paris (to reproduce a possible contamination provided by the molds in slip casting) or CaCO[sub 3]. The obtained results indicate the important role of the firing atmosphere on the precipitation of secondary phases at grain boundary. (orig.).


    Navitsky, Michael A.; Taylor, Joshua O.; Smith, Alexander B.; Slattery, Margaret J.; Deutsch, Steven; Siedlecki, Christopher A.; Manning, Keefe B.


    Platelet adhesion to a polyurethane urea surface is a precursor to thrombus formation within blood-contacting cardiovascular devices, and platelets have been found to adhere strongly to polyurethane surfaces below a shear rate of approximately 500 s−1. The aim of the current work is to determine platelet adhesion properties to the polyurethane urea surface as a function of time varying shear exposure. A rotating disk system is used to study the influence of steady and pulsatile flow conditions (e.g. cardiac inflow and sawtooth waveforms) for platelet adhesion to the biomaterial surface. All experiments retain the same root mean square angular rotation velocity (29.63 rad/s) and waveform period. The disk is rotated in platelet rich bovine plasma for two hours with adhesion quantified by confocal microscopy measurements of immunofluorescently labeled bovine platelets. Platelet adhesion under pulsating flow is found to exponentially decay with increasing shear rate. Adhesion levels are found to depend upon peak platelet flux and shear rate regardless of rotational waveform. In combination with flow measurements, these results may be useful for predicting regions susceptible to thrombus formation within ventricular assist devices. PMID:24721222

  6. Platelet adhesion to polyurethane urea under pulsatile flow conditions. (United States)

    Navitsky, Michael A; Taylor, Joshua O; Smith, Alexander B; Slattery, Margaret J; Deutsch, Steven; Siedlecki, Christopher A; Manning, Keefe B


    Platelet adhesion to a polyurethane urea surface is a precursor to thrombus formation within blood-contacting cardiovascular devices, and platelets have been found to adhere strongly to polyurethane surfaces below a shear rate of approximately 500 s(-1). The aim of the current work is to determine the properties of platelet adhesion to the polyurethane urea surface as a function of time-varying shear exposure. A rotating disk system was used to study the influence of steady and pulsatile flow conditions (e.g., cardiac inflow and sawtooth waveforms) for platelet adhesion to the biomaterial surface. All experiments were conducted with the same root mean square angular rotation velocity (29.63 rad/s) and waveform period. The disk was rotated in platelet-rich bovine plasma for 2 h, with adhesion quantified by confocal microscopy measurements of immunofluorescently labeled bovine platelets. Platelet adhesion under pulsating flow was found to decay exponentially with increasing shear rate. Adhesion levels were found to depend upon peak platelet flux and shear rate, regardless of rotational waveform. In combination with flow measurements, these results may be useful for predicting regions susceptible to thrombus formation within ventricular assist devices.

  7. Defining Platelet Function During Polytrauma (United States)


    using calibrated automated thrombography ( CAT ). 3. Platelet-induced clot contraction and using viscoelastic measures such as TEG with Platelet Mapping...using calibrated automated thrombography ( CAT ) in platelet-rich plasma. 3. Platelet-induced clot contraction and effect on clot structure by platelet...if injury with stable vital signs on initial evaluation.  Pregnancy (confirmed with urine pregnancy testing)  Documented do not resuscitate order

  8. Tension free femoral hernia repair with plug

    Institute of Scientific and Technical Information of China (English)

    Milivoje Vukovi; Neboja Moljevi; Sinia Crnogorac


    Objective: To investigate the conventional technique involves treatment of femoral hernia an approximation inguinal ligament to pectineal ligament. In technique which uses mesh closure for femoral canal without tissue tension. Method: A prospective study from January 01. 2007-May 30. 2009. We analyzed 1 042 patients with inguinal hernia, of which there were 83 patients with 86 femoral hernia. Result: Femoral hernias were present in 7.96% of cases. Males were 13 (15.66%) and 70 women (84.34%). The gender distribution of men: women is 1:5.38. Urgent underwent 69 (83%), and the 14 election (17%) patients. Average age was 63 years, the youngest patient was a 24 and the oldest 86 years. Ratio of right: left hernias was 3.4:1. With bilateral femoral hernias was 3.61% of cases. In 7 patients (8.43%) underwent femoral hernia repair with 9 Prolene plug. Conclusions: The technique of closing the femoral canal with plug a simple. The plug is made from monofilament material and is easily formed. This technique allows the reduction of recurrence and can be used safely, quickly and easily in elective and emergency situations.

  9. Hydrates plugs dissociation in pipelines; Dissociation des bouchons d'hydrates de gaz dans les conduites petrolieres sous-marines

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen Hong, D.


    Natural gas hydrates plugs cause problems during drilling, well operations, production, transportation and processing of oil and gas. Especially, it is a very serious problem in off-shore oil transportation where low temperature and high pressure become more and more favourable to gas hydrate formation as the new production wells are more and more deeper. Up to now, although many studies have been developed concerning the possibility of preventing pipe plugging, there is limited information in open literature on hydrate plugs dissociation and all models in literature are numerically complicated. In this study, hydrate plugs are formed from water in n-dodecane mixture with addition of a dispersant E102B in two different experimental apparatus in order to obtain hydrates plugs with different sizes (diameter of 7, 10.75 and 12 cm). Then, the plugs are dissociated by the method of two-sided depressurization. In this paper, we propose a numerical model which describes the dissociation of gas hydrate plugs in pipelines. The numerical model, which is constructed for cylindrical coordinates and for two-sided pressurization, is based on enthalpy method. We present also an approximate analytical model which has an average error 2.7 % in comparison with the numerical model. The excellent agreement between our experimental results, literature data and the two models shows that the models give a good prediction independently of the pipeline diameter, plug porosity and gas. The simplicity of the analytical model will make it easier in industrial applications. (author)

  10. Clinical application of radiolabelled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, C. (Medical University Luebeck (Federal Republic of Germany). Department of Neurology); Hardeman, M.R. (Amsterdam Univ. (Netherlands). Academisch Ziekenhuis); Henningsen, H. (Heidelberg Univ. (Germany, F.R.). Neurologische Klinik); Petrovici, J.-N. (Cologne-Merheim Hospital (Federal Republic of Germany). Department of Neurology) (eds.)


    The increasing number of therapeutic modalities available for the management of patients with thromboembolic complications, such as fibrinolytic treatment or vascular surgery, require the development of new imaging techniques to provide more information on the xtent, age and activity of the thromboembolic material causing clinical symptoms. Since the introduction of radiolabelling of platelets with indium-111, platelet scintigraphy (PSC) has been used as a tool in the diagnosis of various thromboembolic diseases. During the International Symposium on Radiolabelled Platelets scientists from a variety of medical backgrounds presented their results on the clinical applictions of radiolabelled platelets. The papers presented there have been updated to take account of the latest results before publication in this volume. The papers are grouped into six sections on platelet labelling techniques, radiolabelled platelets in cardiology, monitoring of antiplatelet therapy, platelet scintigraphy in stroke patients, platelet scintigraphy in angiology, and platelet scintigraphy in hematology and other clinical applications, including renal transplant rejection. refs.; figs.; tabs.

  11. Inhibitory Effect of ADP Receptor in Platelets on Clot Formation Assessed by Thromboelastography%血栓弹力图评价血小板ADP受体抑制率对血凝块形成的影响

    Institute of Scientific and Technical Information of China (English)

    黎金庆; 周合冰; 郭金成; 张娟; 曾惠


    目的 了解血小板ADP受体抑制率对血凝块形成的影响,及其与年龄、性别的关系.方法 联用氯吡格雷和阿司匹林的急性冠脉综合征80例,血栓弹力图测定血小板ADP受体抑制率和ADP通道的R时间、K时间、α角、MA值和TMA.结果 80例患者ADP受体抑制率为66.4±24.6%,R时间为0.7±0.4 mm,α角为54.8°±13.7°,MA值为27.1±15.0 mm,TMA为15.9±7.8 min,K时间为6.2±4.6 min(n=51).ADP受体抑制率对R时间无影响(P>0.05);随抑制率增高,a角缩小,MA值降低,TMA缩短,K时间延长并且无K时间病例增多(P<0.05).各年龄段之间、男女患者之间ADP受体抑制率比较均无差别(P>0.05).结论 抑制血小板ADP受体不利于血凝块形成,随抑制率增高,血凝块形成减慢、强度变小;抑制率大小与年龄性别无关.%Objective To study the inhibitory effect of ADP receplor in platelets on clot formation and its associalion with age and gender. Methods 80 patients with acute coronary syndrome were treated with clopidogrel (75 mg) in combination with aspirin ( 100 mg) daily. Inhibitory rate of ADP receptor in platelets were detected by thromboelastography. The following variables of ADP channel were also recorded : R time, K time ,a angle,maximum amplitude (MA) and time to MA ( TMA). Results The inhibitory rate of ADP receptor was 66. 4 ±24. 6% . The R time ,α angle , MA and TMA of ADP channel were 0. 7 ±0. 4 min ,54. 8° ± 13. 7°,27. I ± 15. 0 mm and 15. 9 ±7. 8 min , respectively. The K time was 6. 2 ±4. 6 min( n =51 ) ,with 29 cases having no K time because of MA < 20 mm. Inhibition of ADP receptor had no effect on R time( P > 0. 05).The α angle became smaller,the MA decreased .and the TMA became shorter with the increasing ADP receptor inhibition rate (P <0. 05) . The number of cases having no K time was increased when the K time became longer. Comparison of inhibition rate between different age group, between male and female was not significant

  12. Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets. (United States)

    Etulain, Julia; Negrotto, Soledad; Carestia, Agostina; Pozner, Roberto Gabriel; Romaniuk, María Albertina; D'Atri, Lina Paola; Klement, Giannoula Lakka; Schattner, Mirta


    Acidosis is one of the hallmarks of tissue injury such as trauma, infection, inflammation, and tumour growth. Although platelets participate in the pathophysiology of all these processes, the impact of acidosis on platelet biology has not been studied outside of the quality control of laboratory aggregation assays or platelet transfusion optimization. Herein, we evaluate the effect of physiologically relevant changes in extracellular acidosis on the biological function of platelets, placing particular emphasis on haemostatic and secretory functions. Platelet haemostatic responses such as adhesion, spreading, activation of αIIbβ3 integrin, ATP release, aggregation, thromboxane B2 generation, clot retraction and procoagulant activity including phosphatidilserine exposure and microparticle formation, showed a statistically significant inhibition of thrombin-induced changes at pH of 7.0 and 6.5 compared to the physiological pH (7.4). The release of alpha granule content was differentially regulated by acidosis. At low pH, thrombin or collagen-induced secretion of vascular endothelial growth factor and endostatin were dramatically reduced. The release of von Willebrand factor and stromal derived factor-1α followed a similar, albeit less dramatic pattern. In contrast, the induction of CD40L was not changed by low pH, and P-selectin exposure was significantly increased. While the generation of mixed platelet-leukocyte aggregates and the increased chemotaxis of neutrophils mediated by platelets were further augmented under acidic conditions in a P-selectin dependent manner, the increased neutrophil survival was independent of P-selectin expression. In conclusion, our results indicate that extracellular acidosis downregulates most of the haemostatic platelet functions, and promotes those involved in amplifying the neutrophil-mediated inflammatory response.

  13. Role of dystrophins and utrophins in platelet adhesion process. (United States)

    Cerecedo, Doris; Mondragón, Ricardo; Cisneros, Bulmaro; Martínez-Pérez, Francisco; Martínez-Rojas, Dalila; Rendón, Alvaro


    Platelets are crucial at the site of vascular injury, adhering to the sub-endothelial matrix through receptors on their surface, leading to cell activation and aggregation to form a haemostatic plug. Platelets display focal adhesions as well as stress fibres to contract and facilitate expulsion of growth and pro-coagulant factors contained in the granules and to constrict the clot. The interaction of F-actin with different actin-binding proteins determines the properties and composition of the focal adhesions. Recently, we demonstrated the presence of dystrophin-associated protein complex corresponding to short dystrophin isoforms (Dp71d and Dp71) and the uthophin gene family (Up400 and Up71), which promote shape change, adhesion, aggregation, and granule centralisation. To elucidate participation of both complexes during the platelet adhesion process, their potential association with integrin beta-1 fraction and the focal adhesion system (alpha-actinin, vinculin and talin) was evaluated by immunofluorescence and immunoprecipitation assays. It was shown that the short dystrophin-associated protein complex participated in stress fibre assembly and in centralisation of cytoplasmic granules, while the utrophin-associated protein complex assembled and regulated focal adhesions. The simultaneous presence of dystrophin and utrophin complexes indicates complementary structural and signalling mechanisms to the actin network, improving the platelet haemostatic role.

  14. Design progress on ITER port plug test facility

    Energy Technology Data Exchange (ETDEWEB)

    Levesy, B., E-mail: [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France); Beaumont, B. [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France); Bruno, L.; Cerisier, T. [CNIM, Z.I de Bregaillon, 83507 La Seyne sur Mer (France); Cordier, J.J.; Dammann, A.; Giancarli, L.; Henderson, M. [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France); Romannikov, A. [ITER Agency, Russian Research Center ' Kurchatov Institute' , pl. Kurchatova I., 1, Moscow 123182 (Russian Federation); Rumyantsev, Y. [JSC ' Cryogenmash' , 143907 Moscow reg., Balashikha (Russian Federation); Udintsev, V.S. [ITER Organization, Route de Vinon sur Verdon, 13115 Saint Paul Lez Durance (France)


    To achieve the overall ITER machine availability target, the availability of diagnostics and heating port plugs shall be as high as 99.5%. To fulfill these requirements, it is mandatory to test the port plugs at operating temperature before installation on the machine and after refurbishment. The ITER port plug test facility (PPTF) provides the possibility to test upper and equatorial port plugs before installation on the machine. The port plug test facility is composed of several test stands. These test stands are first used in the domestic agencies and on the ITER Organization site to test the port plugs at the end of manufacturing. Two of these stands are installed later in the ITER hot cell facility to test the port plugs after refurbishment. The port plugs to be tested are the Ion Cyclotron (IC) heating and current drive antennas, Electron Cyclotron (EC) heating and current drive launchers, diagnostics and test blanket modules port plugs. Test stands shall be capable to perform environmental and functional tests. The test stands are composed of one vacuum tank (3.3 m in diameter, 5.6 m long) and the associated heating, vacuum and control systems. The vacuum tank shall achieve an ultimate pressure of 1 Multiplication-Sign 10{sup -5} Pa at 100 Degree-Sign C containing a port plug. The heating system shall provide water at 240 Degree-Sign C and 4.4 MPa to heat up the port plugs. Openings are provided on the back of the vacuum tank to insert probes for the functional tests. This paper describes the tests to be performed on the port plugs and the conceptual design of the port plug test facility. The configuration of the standalone test stands and the integration in the hot cell facility are presented.

  15. Platelet preservation: agitation and containers. (United States)

    van der Meer, Pieter F; de Korte, Dirk


    For platelets to maintain their in vitro quality and in vivo effectiveness, they need to be stored at room temperature with gentle agitation in gas-permeable containers. The mode of agitation affects the quality of the platelets, and a gentle method of agitation, either a circular or a flat bed movement, provides the best results. Tumblers or elliptical agitators induce platelet activation and subsequent damage. As long as the platelets remain in suspension, the agitation speed is not important. Agitation of the platelet concentrates ensures that the platelets are continuously oxygenated, that sufficient oxygen can enter the storage container and that excess carbon dioxide can be expelled. During transportation of platelet concentrates, nowadays over long distances where they are held without controlled agitation, platelets may tolerate a certain period without agitation. However, evidence is accumulating that during the time without agitation, local hypoxia surrounding the platelets may induce irreversible harm to the platelets. Over the decades, more gas-permeable plastics have been used to manufacture platelet containers. The use of different plastics and their influence on the platelet quality both in vitro and in vivo is discussed. The improved gas-permeability has allowed the extension of platelet storage from 3 days in the early 1980s, to currently at least 7 days. In the light of new developments, particularly the introduction of pathogen reduction techniques, the use of platelet additive solutions and the availability of improved automated separators, further (renewed) research in this area is warranted.

  16. Equid herpesvirus type 1 activates platelets.

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    Full Text Available Equid herpesvirus type 1 (EHV-1 causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression and platelet microvesiculation (increased small events double positive for CD41 and Annexin V. Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM. A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis

  17. Role of reactive nitrogen species in blood platelet functions. (United States)

    Olas, Beata; Wachowicz, Barbara


    Blood platelets, in analogy to other circulating blood cells, can generate reactive oxygen/nitrogen species (ROS/RNS) that may behave as second messengers and may regulate platelet functions. Accumulating evidence suggest a role of ROS/RNS in platelet activation. On the other hand, an increased production of ROS/RNS causes oxidative stress, and thus, may contribute to the development of different diseases, including vascular complications, inflammatory and psychiatric illnesses. Oxidative stress in platelets leads to chemical changes in a wide range of their components, and platelet proteins may be initial targets of ROS/RNS action. It has been demonstrated that reaction of proteins with ROS/RNS results in the oxidation and nitration of some amino acid residues, formation of aggregates or fragmentation of proteins. In oxidized proteins new carbonyl groups and protein hydroperoxides are also formed. In platelets, low molecular weight thiols such as glutathione (GSH), cysteine and cysteinylglycine and protein thiols may be also target for ROS/RNS action. This review describes the chemical structure and biological activities of reactive nitrogen species, mainly nitric oxide ((*)NO) and peroxynitrite (ONOO(-)) and their effects on blood platelet functions, and the mechanisms involved in their action on platelets.

  18. Biochemical lesions of platelets stored as concentrates in PVC bags. (United States)

    Krishnan, L K; Mathai, J; Sulochana, P V; Jacob, J; Sivakumar, R


    Acid-base status of platelet suspension during storage is a measure of the gas permeability of the bag material. To assess the efficacy of the bags available in our market to store platelets, we compared biochemical lesions of platelets stored in an Indian polyvinyl chloride (PVC) triple bag against a Japanese PVC bag standardized for 5 days platelet storage. Platelet concentrates prepared in both control and test PVC bags were stored for 72 h. Two ml samples were drawn 1 h after preparation, and then at 24 h intervals, for analysis. Our data show that the mean pH value in the test bags was maintained above 6.5. However, the CO2 tension was high and O2 tension was low. We also analyzed malondialdehyde (MDA) formation which is a measure of arachidonic acid metabolism, and seemed to be unaffected in stored platelets. Lactate dehydrogenase (LDH) was not released into the plasma excessively and hence significant platelet lysis was absent during storage. Hypotonic shock response (HSR) of platelets stored in both test and control bags was comparable, indicating the possibility of satisfactory post-transfusion recovery.

  19. Mechanobiology of Platelets: Techniques to Study the Role of Fluid Flow and Platelet Retraction Forces at the Micro- and Nano-Scale

    Directory of Open Access Journals (Sweden)

    Nathan J. Sniadecki


    Full Text Available Coagulation involves a complex set of events that are important in maintaining hemostasis. Biochemical interactions are classically known to regulate the hemostatic process, but recent evidence has revealed that mechanical interactions between platelets and their surroundings can also play a substantial role. Investigations into platelet mechanobiology have been challenging however, due to the small dimensions of platelets and their glycoprotein receptors. Platelet researchers have recently turned to microfabricated devices to control these physical, nanometer-scale interactions with a higher degree of precision. These approaches have enabled exciting, new insights into the molecular and biomechanical factors that affect platelets in clot formation. In this review, we highlight the new tools used to understand platelet mechanobiology and the roles of adhesion, shear flow, and retraction forces in clot formation.

  20. Mechanobiology of platelets: techniques to study the role of fluid flow and platelet retraction forces at the micro- and nano-scale. (United States)

    Feghhi, Shirin; Sniadecki, Nathan J


    Coagulation involves a complex set of events that are important in maintaining hemostasis. Biochemical interactions are classically known to regulate the hemostatic process, but recent evidence has revealed that mechanical interactions between platelets and their surroundings can also play a substantial role. Investigations into platelet mechanobiology have been challenging however, due to the small dimensions of platelets and their glycoprotein receptors. Platelet researchers have recently turned to microfabricated devices to control these physical, nanometer-scale interactions with a higher degree of precision. These approaches have enabled exciting, new insights into the molecular and biomechanical factors that affect platelets in clot formation. In this review, we highlight the new tools used to understand platelet mechanobiology and the roles of adhesion, shear flow, and retraction forces in clot formation.

  1. Effect of shear-thinning behaviour on liquid-liquid plug flow in microchannels (United States)

    Roumpea, Evangelia; Chinaud, Maxime; Weheliye, Weheliye Hashi; Angeli, Panagiota; Kahouadji, Lyes; Matar, Omar K.


    The present work investigates the dynamics of plug formation of shear-thinning solutions in a 200 μm microchannel using a two-colour micro-PIV system. Measurements, including phase-averaged velocity fields, have been conducted both at the T-junction inlet and the main channel to enhance understanding of non-Newtonian liquid-liquid flows. Two aqueous glycerol solutions containing xanthan gum are used as the non-Newtonian fluids while 5 cSt silicone oil is the Newtonian phase. The current experimental results revealed a pronounced impact of the xanthan gum (shear-thinning behaviour) on the flow pattern transition boundaries, and enhance the fluid flowrates where plug flow occurred. The addition of polymer resulted also in different hydrodynamic characteristics such as a bullet-shaped plug and an increased film thickness between the plug and the wall. In the present work, the technique allows to capture the velocity field of both phases simultaneously. Experimental results are compared with the numerical simulations provided by the code BLUE. Project funded under the UK Engineering and Physical Sciences Research Council (EPSRC) Programme Grant MEMPHIS.

  2. A plug with infinite order and some exotic 4-manifolds

    CERN Document Server

    Tange, Motoo


    Every exotic pair in 4-dimension is obtained each other by twisting a {\\it cork} or {\\it plug} which are codimension 0 submanifolds embedded in the 4-manifolds. The twist was an involution on the boundary of the submanifold. We define cork (or plug) with order $p\\in {\\Bbb N}\\cup \\{\\infty\\}$ and show there exists a plug with infinite order. Furthermore we show twisting $(P,\\varphi^2)$ gives to enlargements of $P$ compact exotic manifolds with boundary.

  3. The trophoblast plug during early pregnancy: a deeper insight


    Weiss, Gregor; Sundl, Monika; Glasner, Andreas; Huppertz, Berthold; Moser, Gerit


    During the first trimester of pregnancy, foetal endovascular trophoblasts invade into maternal spiral arteries, accumulate and form plugs in the lumen of the vessels. These plugs only allow blood plasma to seep through. Hence, during the first trimester of pregnancy, a first flow of fluids through the placental intervillous space is established, resulting in a physiological oxygen gradient between mother and foetus. The trophoblast plugs block spiral arteries until the beginning of the second...

  4. SpaceWire Plug and Play (United States)

    Rakow, Glenn; McGuirk, Patrick; Kimmery, Clifford; Jaffe, Paul


    The ability to rapidly deploy inexpensive satellites to meet tactical goals has become an important goal for military space systems. In fact, Operationally Responsive Space (ORS) has been in the spotlight at the highest levels. The Office of the Secretary of Defense (OSD) has identified that the critical next step is developing the bus standards and modular interfaces. Historically, satellite components have been constructed based on bus standards and standardized interfaces. However, this has not been done to a degree, which would allow the rapid deployment of a satellite. Advancements in plug-and-play (PnP) technologies for terrestrial applications can serve as a baseline model for a PnP approach for satellite applications. Since SpaceWire (SpW) has become a de facto standard for satellite high-speed (greater than 200Mbp) on-board communications, it has become important for SpW to adapt to this Plug and Play (PnP) environment. Because SpW is simply a bulk transport protocol and lacks built-in PnP features, several changes are required to facilitate PnP with SpW. The first is for Host(s) to figure out what the network looks like, i.e., how pieces of the network, routers and nodes, are connected together; network mapping, and to receive notice of changes to the network. The second is for the components connected to the network to be understood so that they can communicate. The first element, network topology mapping & change of status indication, is being defined (topic of this paper). The second element describing how components are to communicate has been defined by ARFL with the electronic data sheets known as XTEDS. The first element, network mapping, is recent activities performed by Air Force Research Lab (ARFL), Naval Research Lab (NRL), NASA and US industry (Honeywell, Clearwater, FL, and others). This work has resulted in the development of a protocol that will perform the lower level functions of network mapping and Change Of Status (COS) indication

  5. Electric powered vehicle: Tulip without direct plug

    Energy Technology Data Exchange (ETDEWEB)



    Here is described the electric powered vehicle, called Tulip (for Urban Transport, free, Individual and Public) developed by PSA Peugeot Citroen, french automobile company. Its electric characteristics are based on induction. The refill system, by induction allows to the subscriber not to be concerned about it. On arriving to the relay station, it only takes to position the vehicle on the centre which puts in relation a captor with the inductor coupled to a generator plugged into the mains. The cadmium-nickel battery offers a 9.6 Kw power and gives a range longer than 60 kilometers. (N.C.). 1 fig., 1 photo.

  6. Testing and plugging power plant heat exchangers

    Energy Technology Data Exchange (ETDEWEB)

    Sutor, F. [Expando Seal Tools, Inc., Montgomeryville, PA (United States)


    Heat Exchanger tubes fail for any number of reasons including but certainly not limited to the cumulative effects of corrosion, erosion, thermal stress and fatigue. This presentation will attempt to identify the most common techniques for determining which tubes are leaking and then introduce the products in use to plug the leaking tubes. For the sake of time I will limit the scope of this presentation to include feedwater heaters and secondary system heat exchangers such as Hydrogen Coolers, Lube Oil Coolers, and nuclear Component Cooling Water, Emergency Cooling Water, Regenerative Heat Recovery heat exchangers.

  7. Plug ‘n’ Play with DNA

    DEFF Research Database (Denmark)

    Lund, Anne Mathilde; Andreasen, Elisa W.; Korgaard, Jaide V.;

    Synthetic biology has evolved dramatically within the past decade, which calls for a revolution of the Standard Assembly method that makes the foundation of BioBricks. We believe that iGEM should be about fast assembly of BioBricks, where any thinkable part, device or existing BioBrick can be com...... be combined for any type of organism within one day. Therefore, we have designed a new BioBrick Kit based on a novel assembly standard; called “Plug 'n' Play with DNA”....

  8. The Platelet and Platelet Function Testing in Liver Disease

    NARCIS (Netherlands)

    Hugenholtz, Greg G. C.; Porte, Robert J.; Lisman, Ton


    Patients who have liver disease commonly present with alterations in platelet number and function. Recent data have questioned the contribution of these changes to bleeding complications in these patients. Modern tests of platelet function revealed compensatory mechanisms for the decreased platelet

  9. Investigation of platelet function and platelet disorders using flow cytometry. (United States)

    Rubak, Peter; Nissen, Peter H; Kristensen, Steen D; Hvas, Anne-Mette


    Patients with thrombocytopenia or platelet disorders are at risk of severe bleeding. We report the development and validation of flow cytometry assays to diagnose platelet disorders and to assess platelet function independently of platelet count. The assays were developed to measure glycoprotein levels (panel 1) and platelet function (panel 2) in sodium citrated blood. Twenty healthy volunteers and five patients diagnosed with different platelet disorders were included. Glycoprotein expression levels of the receptors Ia, Ib, IIb, IIIa and IX were measured and normalised with forward scatter (FS) as a measurement of platelet size. Platelet function was assessed by CD63, P-selectin and bound fibrinogen in response to arachidonic acid, adenosine diphosphate (ADP), collagen-related peptide, ristocetin and thrombin receptor-activation peptide-6. All patients except one with suspected δ-granule defect showed aberrant levels of glycoproteins in panel 1. Glanzmann's thrombasthenia and genetically verified Bernard-Soulier syndrome could be diagnosed using panel 1. All patients showed reduced platelet function according to at least one agonist. Using panel 2 it was possible to diagnose Bernard-Soulier syndrome, δ-granule defect and GPVI disorder. By combining the two assays, we were able to diagnose different platelet disorders and investigate platelet function independent of platelet count.

  10. Reproducibility of Manual Platelet Estimation Following Automated Low Platelet Counts

    Directory of Open Access Journals (Sweden)

    Zainab S Al-Hosni


    Full Text Available Objectives: Manual platelet estimation is one of the methods used when automated platelet estimates are very low. However, the reproducibility of manual platelet estimation has not been adequately studied. We sought to assess the reproducibility of manual platelet estimation following automated low platelet counts and to evaluate the impact of the level of experience of the person counting on the reproducibility of manual platelet estimates. Methods: In this cross-sectional study, peripheral blood films of patients with platelet counts less than 100 × 109/L were retrieved and given to four raters to perform manual platelet estimation independently using a predefined method (average of platelet counts in 10 fields using 100× objective multiplied by 20. Data were analyzed using intraclass correlation coefficient (ICC as a method of reproducibility assessment. Results: The ICC across the four raters was 0.840, indicating excellent agreement. The median difference of the two most experienced raters was 0 (range: -64 to 78. The level of platelet estimate by the least-experienced rater predicted the disagreement (p = 0.037. When assessing the difference between pairs of raters, there was no significant difference in the ICC (p = 0.420. Conclusions: The agreement between different raters using manual platelet estimation was excellent. Further confirmation is necessary, with a prospective study using a gold standard method of platelet counts.

  11. Knowledge-Based System to Support Plug Load Management (United States)

    National Aeronautics and Space Administration — Electrical plug loads comprise an increasingly larger share of building energy consumption as improvements have been made to Heating, Ventilation, and Air...

  12. Emerging Evidence for Platelets as Immune and Inflammatory Effector Cells

    Directory of Open Access Journals (Sweden)

    Matthew Thomas Rondina


    Full Text Available While traditionally recognized for their roles in hemostatic pathways, emerging evidence demonstrates that platelets have previously unrecognized, dynamic roles that span the immune continuum. These newly-recognized platelet functions, including the secretion of immune mediators, interactions with endothelial cells, monocytes, and neutrophils, toll-like receptor (TLR mediated responses, and induction of neutrophil extracellular trap (NET formation, bridge thrombotic and inflammatory pathways and contribute to host defense mechanisms against invading pathogens. In this focused review, we highlight several of these emerging aspects of platelet biology and their implications in clinical infectious syndromes.

  13. Mechanistic Understanding of Microbial Plugging for Improved Sweep Efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Steven Bryant; Larry Britton


    Microbial plugging has been proposed as an effective low cost method of permeability reduction. Yet there is a dearth of information on the fundamental processes of microbial growth in porous media, and there are no suitable data to model the process of microbial plugging as it relates to sweep efficiency. To optimize the field implementation, better mechanistic and volumetric understanding of biofilm growth within a porous medium is needed. In particular, the engineering design hinges upon a quantitative relationship between amount of nutrient consumption, amount of growth, and degree of permeability reduction. In this project experiments were conducted to obtain new data to elucidate this relationship. Experiments in heterogeneous (layered) beadpacks showed that microbes could grow preferentially in the high permeability layer. Ultimately this caused flow to be equally divided between high and low permeability layers, precisely the behavior needed for MEOR. Remarkably, classical models of microbial nutrient uptake in batch experiments do not explain the nutrient consumption by the same microbes in flow experiments. We propose a simple extension of classical kinetics to account for the self-limiting consumption of nutrient observed in our experiments, and we outline a modeling approach based on architecture and behavior of biofilms. Such a model would account for the changing trend of nutrient consumption by bacteria with the increasing biomass and the onset of biofilm formation. However no existing model can explain the microbial preference for growth in high permeability regions, nor is there any obvious extension of the model for this observation. An attractive conjecture is that quorum sensing is involved in the heterogeneous bead packs.

  14. Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of beta(1) and B-2 integrins

    NARCIS (Netherlands)

    P.A.D.C. Martins; J.M. van Gils; A. Mol; P.L. Hordijk; J.J. Zwaginga


    Human monocytes adhere to activated platelets, resulting in the formation of platelet-monocyte complexes (PMC). Complex formation depends on the interaction between platelet-displayed P-selectin and the specific ligand for P-selectin on leukocytes, P-selectin glycoprotein ligand-1 (PSGL-1). We have

  15. Effects of local application of platelet-rich plasma and guided tissue regeneration on stability of implants


    Duka Miloš; Lazić Z.; Bubalo Marija; Tatić Z.; Đurđević D.; Matić Smiljana


    Osseointegration is a result of cellular migration, differentiation, bone formation, and bone remodelling on the surface of an implant. Each of these processes depends on platelets and blood coagulum. Platelet-rich plasma (PRP) is used to improve osseointegration and stability of implants. It is a blood fraction produced in a centrifuge which contains a high concentration of platelets. Platelets contain numerous growth factors which influence tissue reactions. The aim of the research is to te...

  16. Deep Space Habitat Wireless Smart Plug (United States)

    Morgan, Joseph A.; Porter, Jay; Rojdev, Kristina; Carrejo, Daniel B.; Colozza, Anthony J.


    NASA has been interested in technology development for deep space exploration, and one avenue of developing these technologies is via the eXploration Habitat (X-Hab) Academic Innovation Challenge. In 2013, NASA's Deep Space Habitat (DSH) project was in need of sensors that could monitor the power consumption of various devices in the habitat with added capability to control the power to these devices for load shedding in emergency situations. Texas A&M University's Electronic Systems Engineering Technology Program (ESET) in conjunction with their Mobile Integrated Solutions Laboratory (MISL) accepted this challenge, and over the course of 2013, several undergraduate students in a Capstone design course developed five wireless DC Smart Plugs for NASA. The wireless DC Smart Plugs developed by Texas A&M in conjunction with NASA's Deep Space Habitat team is a first step in developing wireless instrumentation for future flight hardware. This paper will further discuss the X-Hab challenge and requirements set out by NASA, the detailed design and testing performed by Texas A&M, challenges faced by the team and lessons learned, and potential future work on this design.

  17. Laboratory Research on Fracture-Supported Shielding Temporary Plugging Drill-In Fluid for Fractured and Fracture-Pore Type Reservoirs

    Directory of Open Access Journals (Sweden)

    Dawei Liu


    Full Text Available Based on fractures stress sensitivity, this paper experimentally studies fracture-supported shielding temporary plugging drill-in fluid (FSDIF in order to protect fractured and fracture-pore type formation. Experimental results show the FSDIF was better than the CDIF for protecting fractured and fracture-pore type reservoir and the FSDIF temporary plugging rate was above 99%, temporary plugging ring strength was greater than 15 MPa, and return permeability was 91.35% and 120.83% before and after acidizing, respectively. The reasons for the better reservoir protection effect were analyzed. Theoretical and experiment studies conducted indicated that the FSDIF contained acid-soluble and non-acid-soluble temporary shielding agents; non-acid-soluble temporary shielding agents had high hardness and temporary plugging particles size was matched to the formation fracture width and pore throat size.

  18. Biologically formed calcium carbonate, a durable plugging agent for enhanced oil recovery

    Energy Technology Data Exchange (ETDEWEB)

    Nemati, M. [University of Saskatchewan, Dept. of Chemical Engineering, Saskatoon, SK (Canada); Voordouw, G. [University of Calgary, Dept. of Biological Sciences, Calgary, AB (Canada)


    The use of bacterially precipitated inorganic compounds such as calcium carbonate and silica have been suggested as an effective method for selective plugging of reservoirs as a means to improve microscopic and volumetric sweep efficiencies within a given geological formation. In this paper controlled enzymatic and bacterial formation of calcium carbonate were studied using a purified urease enzyme and a bacterium isolated from a Canadian oil field. Results showed that the quantity of produced calcium carbonate in the presence of bacteria was dependent on urea concentration. The highest amount achieved was 15 g/L urea. Enzymatically, the maximum concentration of calcium carbonate was 2.6 times higher than that achieved in the presence of bacteria (57.6 g/L vs 21.5 g/L). The production of calcium carbonate appeared to be less sensitive to temperature in the presence of bacteria, whereas production rates were enhanced with the urease enzyme as the temperature was increased from 20 degrees C to 50 degrees C. Plugging studies in unconsolidated porous media and in a core-flooding system with Beria sandstone indicated that in situ formation of calcium carbonate could effectively decrease the permeability of the porous media. Nevertheless, it should be noted that plugging by biomass is not permanent, and permeabilities will increase as degradation of bacterial cells progresses. 5 refs., 4 tabs., 1 fig.

  19. Mean platelet volume and mean platelet volume/platelet count ratio ...

    African Journals Online (AJOL)

    Amira M. Elsayed


    Mar 30, 2016 ... Abstract The mean platelet volume (MPV) is a laboratory marker associated with platelet func- tion and activity. .... the first 24 h of presentation to the emergency department. Severity of ..... J Neurol Neurosurg Psychiatry.

  20. Glatiramer acetate (copaxone modulates platelet activation and inhibits thrombin-induced calcium influx: possible role of copaxone in targeting platelets during autoimmune neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Sarah C Starossom

    Full Text Available BACKGROUND: Glatiramer acetate (GA, Copaxone, Copolymer-1 is an FDA approved drug for the treatment of MS and it is very effective in suppressing neuroinflammation in experimental autoimmune encephalitis (EAE, an animal model of MS. Although this drug was designed to inhibit pathogenic T cells, the exact mechanism of EAE/MS suppression by GA is still not well understood. Previously we presented evidence that platelets become activated and promote neuroinflammation in EAE, suggesting a possible pathogenic role of platelets in MS and EAE. We hypothesized that GA could inhibit neuroinflammation by affecting not only immune cells but also platelets. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of GA on the activation of human platelets in vitro: calcium influx, platelet aggregation and expression of activation markers. Our results in human platelets were confirmed by in-vitro and in-vivo studies of modulation of functions of platelets in mouse model. We found that GA inhibited thrombin-induced calcium influx in human and mouse platelets. GA also decreased thrombin-induced CD31, CD62P, CD63, and active form of αIIbβ3 integrin surface expression and formation of platelet aggregates for both mouse and human platelets, and prolonged the bleeding time in mice by 2.7-fold. In addition, we found that GA decreased the extent of macrophage activation induced by co-culture of macrophages with platelets. CONCLUSIONS: GA inhibited the activation of platelets, which suggests a new mechanism of GA action in suppression of EAE/MS by targeting platelets and possibly preventing their interaction with immune cells such as macrophages. Furthermore, the reduction in platelet activation by GA may have additional cardiovascular benefits to prevent thrombosis.

  1. The biology of the platelet with special reference to inflammation, wound healing and immunity. (United States)

    Nurden, Alan T


    While platelets have long been known to be essential for maintaining hemostasis in the vasculature, their role in tissue repair, inflammation and innate and adaptive immunity is a more recent science. The ability of platelets to attach to the vessel wall, form aggregates and promote fibrin formation, key elements of blood clotting, has been said to both favor and dampen inflammation, to fight infection and to assure an adequate immune response. To fulfill their different roles platelets often synchronize with leukocytes and cells of the immune system. But just as the molecular pathways of platelets in preventing blood loss can lead to arterial thrombosis and stroke if occurring in an uncontrolled manner, the failure to control inflammation can lead to sepsis and inadequate platelet function and can aggravate many major illnesses. This review is aimed to present a global picture of multifaceted platelet biology and platelet involvement in selected non-hemostatic events.

  2. Innovative cement plug setting process reduces risk and lowers NPT

    Energy Technology Data Exchange (ETDEWEB)

    Marriott, T.; Rogers, H.; Lloyd, S.; Quinton, C. [Halliburton Energy Services, Calgary, AB (Canada); Tetrault, N. [Apache Canada, Calgary, AB (Canada)


    With increased drilling in mature fields and unconventional reservoirs, Canadian operators are experiencing a higher rate of lost circulation events. When drilling into lower fracture-gradient zones, operators face the risk of drilling through shallower depleted zones. The unique challenges associated with setting cement plugs in such open hole wells were described. The best solution to address lost circulation events is a properly designed cement slurry where cement can be squeezed into the lost circulation zones to strengthen the wellbore when set. The cement plug is drilled through, leaving the residual cement setting inside the problem zones. Since cement plugs are used for a wide range of reasons, such as healing losses, abandonment, and directional drilling, it is important that a competent cement plug is placed the first time. This paper presented a newly developed tool and a special process designed to meet the challenges associated with setting cement plugs. It is based on a tubing-release tool (TRT) in which a sacrificial tubing is placed into the lost circulation zone to balance the cement plug. The sacrificial tubing is released from the drillstring and remains in the wellbore. The TRT has been used as a plug-setting aid for lost-circulation plugs; shallow-water shut-off; kick-off plug placement; and multizone plugs to abandon. An overview of the TRT features was presented. The tool and process has been used by more than 20 operating companies around the world to successfully place cement plugs downhole on the first attempt. The disconnect has been used successfully in more than 120 wells throughout North and South America, Europe, the Middle East, and Australia. It has proven to lower the risk and non-productive time associated with drilling in mature fields and unconventional reservoirs. 7 refs., 5 figs.

  3. Fibrin/platelet plug counteracts cutaneous wound contraction: the hypothesis of "skipping stone". (United States)

    Farahani, Ramin Mostofi Zadeh


    Cutaneous wound contraction and epithelialization act collaboratively to minimize the exposed wound surface. However excessive wound contraction is undesirable due to the resultant disfigurement and scarring. Fibrin clot has greater stiffness than surrounding tissue and mechanical strain further enhances its stiffness. On the contrary, skin exhibits diminished stiffness when affected by high strain rates. Therefore during early stages of wound healing, the contractile wound border is confronted by fibrin clot forming a high strain region in the interface of contractile tissue and fibrin clot--which is evidenced by computer simulation. Due to the stress relaxation property of skin, the contractile strain is partly neutralized. Meanwhile, gradually the stiffness of fibrin clot decreases which is followed by another cycle of wound contraction. This cyclic pattern of contraction resembles the movement of a stone over water or "skipping stone". The stone bounces repeatedly when thrown across the surface of water with reduction of jumping altitude with each bounce till the stone stops completely. This hypothesis is further supported by the observed initial delay in wound contraction and the chronological correlation of enhanced wound contraction with loss of superficial eschar and substitution of fibrin clot with granulation tissue. Also there is evidence that fibrin inhibits fibroblast-mediated contraction of collagen. Furthermore, modest increase in wound contraction rate in fibrinogen deficient mice and fibrin-mediated diminished wound contraction are agreement with the proposed hypothesis.

  4. Actively induced platelet-bound IgG associated with thrombocytopenia in the marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Gengozian, N.; McLaughlin, C.L.


    Interspecies platelet immunizations among marmosets lead to antibody formation to the donor platelets and a profound thrombocytopenia, which when associated with anemia may result in death of the animal. This actively induced immonologic thrombocytopenia closely resembles two clinical disease entities manifesting autoimmune thrombocytopenia, posttransfusion purpura and idiopathic thrombocytopenic purpura. Although antibody to donor-type platelets could be demonstrated readily, antihost activity was most often nondetectable or, when present, was in very low titer. A consistent finding was the appearance of IgG on the host's platelets shortly after immunization and concomitant with the appearance of antidonor platelet antibody. In 3 of 13 immunized animals thromoocytopenia did not occur even though antibody was formed and the host's platelets became IgG positive. In those animals that recovered from the induced thrombocytopenia IgG-positive platelets were found for periods ranging from 30 to greater than 100 days. Splenectomy before or after immunization did not alter the sequential development of antibody formation, appearance of IgG-positive platelets, and thrombocytopenia. Eluates prepared from IgG-positive platelets contained IgG and platelet antigens; the eluted IgG could attach nonspecifically to platelets of host or donor (immunizing) type, in contrast to the species specificity demonstrated for IgG eluted from platelets that had been reacted in vitro with specific antibody. Platelets in a few normal, nonimmunized marmosets were found to have signficant amounts of IgG on their surface, comparable to that observed in the immunized animal; interestingly, such IgG-positive platelets were found among imported but not laboratory-bred marmosets.

  5. Plug-and-playable fluorescent cell imaging modular toolkits using the bacterial superglue, SpyTag/SpyCatcher. (United States)

    Moon, Hyojin; Bae, Yoonji; Kim, Hansol; Kang, Sebyung


    Simple plug-and-playable fluorescent cell imaging modular toolkits are established using the bacterial superglue SpyTag/SpyCatcher protein ligation system. A variety of affibody-fluorescent protein conjugates (AFPCs) are post-translationally generated via the isopeptide bond formation, and each AFPC effectively recognizes and binds to its targeting cells, visualizing them with selective colors on demand.

  6. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

    Whitehorn, James; Rodriguez Roche, Rosmari; Guzman, Maria G


    of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity...

  7. Platelets in leucocyte recruitment and function. (United States)

    Rossaint, Jan; Zarbock, Alexander


    Platelets have a longstanding recognition as an essential cellular component of the coagulation system. However, substantial research over the last decade has added another important aspect to platelet function in that they are also an integral part of the innate immune system. Complex organisms are facing a constant threat of infections by invading pathogens, and they have developed a sophisticated and elegant measure to combat this threat, namely the immune system. Leucocyte recruitment to sites of infections is an essential step at the forefront of the immune response. Platelets have been shown to be involved in several steps of this process and they are an integrated connecting element among haemostasis, host defence, and additional immunological functions (e.g. neutrophil extracellular traps formation). However, the immune system also requires a tight regulation, as an overshooting immune response carries the risk of harming the host itself. This review aims at highlighting the unique features and molecular mechanisms that allow for the interactions of platelets and leucocytes and the regulation of this process. Furthermore, this article identifies the functional relevance of these events for the immune response.

  8. Plug and Play Process Control of a District Heating System

    DEFF Research Database (Denmark)

    Trangbaek, Klaus; Knudsen, Torben; Skovmose Kallesøe, Carsten


    The main idea of plug and play process control is to initialise and reconfigure control systems automatically. In this paper these ideas are applied to a scaled laboratory model of a district heating pressure control system.  First of all this serves as a concrete example of plug and play control...

  9. Hybrid and Plug-In Electric Vehicles (Brochure)

    Energy Technology Data Exchange (ETDEWEB)


    Hybrid and plug-in electric vehicles use electricity as their primary fuel or to improve the efficiency of conventional vehicle designs. These vehicles can be divided into three categories: hybrid electric vehicles (HEVs), plug-in hybrid electric vehicles (PHEVs), all-electric vehicles (EVs). Together, they have great potential to cut U.S. petroleum use and vehicle emissions.

  10. Plug-in hybrid electric vehicles in dynamical energy markets

    NARCIS (Netherlands)

    Kessels, J.T.B.A.; Bosch, P.P.J. van den


    The plug-in hybrid electric vehicle allows vehicle propulsion from multiple internal power sources. Electric energy from the grid can be utilized by means of the plug-in connection. An on-line energy management (EM) strategy is proposed to minimize the costs for taking energy from each power source.

  11. Developing quality standards for physical properties of mineral wool plugs

    NARCIS (Netherlands)

    Blok, C.; Berg, van den C.C.; Winkel, van A.


    The KIWA certification guidelines for mineral wool products contain standards for slabs and blocks. Propagators would like to introduce quality standards for mineral wool plugs as well. Main concerns were effects of too dense plugs on plant growth, and handling problems with too fluffy or broken

  12. National Plug-In Electric Vehicle Infrastructure Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Eric Wood, Clément Rames, Matteo Muratori, Sesha Raghavan, and Marc Melaina


    This report addresses the fundamental question of how much plug-in electric vehicle (PEV) charging infrastructure—also known as electric vehicle supply equipment (EVSE)—is needed in the United States to support both plug-in hybrid electric vehicles (PHEVs) and battery electric vehicles (BEVs).

  13. Plug-in hybrid electric vehicles in dynamical energy markets

    NARCIS (Netherlands)

    Kessels, J.T.B.A.; Bosch, P.P.J. van den


    The plug-in hybrid electric vehicle allows vehicle propulsion from multiple internal power sources. Electric energy from the grid can be utilized by means of the plug-in connection. An on-line energy management (EM) strategy is proposed to minimize the costs for taking energy from each power source.

  14. California Statewide Plug-In Electric Vehicle Infrastructure Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Melaina, Marc; Helwig, Michael


    The California Statewide Plug-In Electric Vehicle Infrastructure Assessment conveys to interested parties the Energy Commission’s conclusions, recommendations, and intentions with respect to plug-in electric vehicle (PEV) infrastructure development. There are several relatively low-risk and high-priority electric vehicle supply equipment (EVSE) deployment options that will encourage PEV sales and

  15. beta-Dystroglycan modulates the interplay between actin and microtubules in human-adhered platelets. (United States)

    Cerecedo, Doris; Cisneros, Bulmaro; Suárez-Sánchez, Rocío; Hernández-González, Enrique; Galván, Iván


    To maintain the continuity of an injured blood vessel, platelets change shape, secrete granule contents, adhere, aggregate, and retract in a haemostatic plug. Ordered arrays of microtubules, microfilaments, and associated proteins are responsible for these platelet responses. In full-spread platelets, microfilament bundles in association with other cytoskeleton proteins are anchored in focal contacts. Recent studies in migrating cells suggest that co-ordination and direct physical interaction of microtubules and actin network modulate adhesion development. In platelets, we have proposed a feasible association between these two cytoskeletal systems, as well as the participation of the dystrophin-associated protein complex, as part of the focal adhesion complex. The present study analysed the participation of microtubules and actin during the platelet adhesion process. Confocal microscopy, fluorescence resonance transfer energy and immunoprecipitation assays were used to provide evidence of a cross-talk between these two cytoskeletal systems. Interestingly, beta-dystroglycan was found to act as an interplay protein between actin and microtubules and an additional communication between these two cytoskeleton networks was maintained through proteins of focal adhesion complex. Altogether our data are indicative of a dynamic co-participation of actin filaments and microtubules in modulating focal contacts to achieve platelet function.

  16. Lysyl oxidase is associated with increased thrombosis and platelet reactivity. (United States)

    Matsuura, Shinobu; Mi, Rongjuan; Koupenova, Milka; Eliades, Alexia; Patterson, Shenia; Toselli, Paul; Thon, Jonathan; Italiano, Joseph E; Trackman, Philip C; Papadantonakis, Nikolaos; Ravid, Katya


    Lysyl oxidase (LOX) is overexpressed in various pathologies associated with thrombosis, such as arterial stenosis and myeloproliferative neoplasms (MPNs). LOX is elevated in the megakaryocytic lineage of mouse models of MPNs and in patients with MPNs. To gain insight into the role of LOX in thrombosis and platelet function without compounding the influences of other pathologies, transgenic mice expressing LOX in wild-type megakaryocytes and platelets (Pf4-Lox(tg/tg)) were generated. Pf4-Lox(tg/tg) mice had a normal number of platelets; however, time to vessel occlusion after endothelial injury was significantly shorter in Pf4-Lox(tg/tg) mice, indicating a higher propensity for thrombus formation in vivo. Exploring underlying mechanisms, we found that Pf4-Lox(tg/tg) platelets adhere better to collagen and have greater aggregation response to lower doses of collagen compared with controls. Platelet activation in response to the ligand for collagen receptor glycoprotein VI (cross-linked collagen-related peptide) was unaffected. However, the higher affinity of Pf4-Lox(tg/tg) platelets to the collagen sequence GFOGER implies that the collagen receptor integrin α2β1 is affected by LOX. Taken together, our findings demonstrate that LOX enhances platelet activation and thrombosis.

  17. Experimental plug and play quantum coin flipping (United States)

    Pappa, Anna; Jouguet, Paul; Lawson, Thomas; Chailloux, André; Legré, Matthieu; Trinkler, Patrick; Kerenidis, Iordanis; Diamanti, Eleni


    Performing complex cryptographic tasks will be an essential element in future quantum communication networks. These tasks are based on a handful of fundamental primitives, such as coin flipping, where two distrustful parties wish to agree on a randomly generated bit. Although it is known that quantum versions of these primitives can offer information-theoretic security advantages with respect to classical protocols, a demonstration of such an advantage in a practical communication scenario has remained elusive. Here we experimentally implement a quantum coin flipping protocol that performs strictly better than classically possible over a distance suitable for communication over metropolitan area optical networks. The implementation is based on a practical plug and play system, developed by significantly enhancing a commercial quantum key distribution device. Moreover, we provide combined quantum coin flipping protocols that are almost perfectly secure against bounded adversaries. Our results offer a useful toolbox for future secure quantum communications.

  18. Plugging criteria for WWER SG tubes

    Energy Technology Data Exchange (ETDEWEB)

    Papp, L.; Wilam, M. [Vitkovice NPP Services (Switzerland); Herman, M. [Vuje, Trnava (Slovakia)


    At operated Czech and Slovak nuclear power plants the 80 % criteria for crack or other bulk defect depth is used for steam generator heat exchanging tubes plugging. This criteria was accepted as the recommendation of designer of WWER steam generators. Verification of this criteria was the objective of experimental program performed by Vitkovice, J.S.C., UJV Rez, J.S.C. and Vuje Trnava, J.S.C .. Within this program the following factors were studied: (1) Influence of secondary water chemistry on defects initiation and propagation, (2) Statistical evaluation of corrosion defects progression at operated SG, and (3) Determination of critical pressure for tube rupture as a function of eddy current indications. In this presentation items (2) and (3) are considered.

  19. IκB kinase phosphorylation of SNAP-23 controls platelet secretion. (United States)

    Karim, Zubair A; Zhang, Jinchao; Banerjee, Meenakshi; Chicka, Michael C; Al Hawas, Rania; Hamilton, Tara R; Roche, Paul A; Whiteheart, Sidney W


    Platelet secretion plays a key role in thrombosis, thus the platelet secretory machinery offers a unique target to modulate hemostasis. We report the regulation of platelet secretion via phosphorylation of SNAP-23 at Ser95. Phosphorylation of this t-soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) occurs upon activation of known elements of the platelet signaling cascades (ie, phospholipase C, [Ca(2+)]i, protein kinase C) and requires IκB kinase (IKK)-β. Other elements of the nuclear factor κB/IκB cascade (ie, IKK-α,-β,-γ/NEMO and CARMA/MALT1/Bcl10 complex) are present in anucleate platelets and IκB is phosphorylated upon activation, suggesting that this pathway is active in platelets and implying a nongenomic role for IKK. Inhibition of IKK-β, either pharmacologically (with BMS-345541, BAY11-7082, or TPCA-1) or by genetic manipulation (platelet factor 4 Cre:IKK-β(flox/flox)), blocked SNAP-23 phosphorylation, platelet secretion, and SNARE complex formation; but, had no effect on platelet morphology or other metrics of platelet activation. Consistently, SNAP-23 phosphorylation enhanced membrane fusion of SNARE-containing proteoliposomes. In vivo studies with IKK inhibitors or platelet-specific IKK-β knockout mice showed that blocking IKK-β activity significantly prolonged tail bleeding times, suggesting that currently available IKK inhibitors may affect hemostasis.

  20. Evaluation of electrical aggregometry: comparison with optical aggregometry, secretion of ATP, and accumulation of radiolabeled platelets

    Energy Technology Data Exchange (ETDEWEB)

    Ingerman-Wojenski, C.; Smith, J.B.; Silver, M.J.


    Platelet aggregation has been most commonly studied in vitro by measuring increases in light transmission as platelets aggregate in PRP (platelet-rich plasma). Recently, an electrical impedance method for measuring platelet aggregation has been introduced. This method can be used with either PRP or whole blood and measures an increase in impedance across electrodes placed in the blood samples as platelets accumulate on them. Results obtained by the two methods were compared using ADP and collagen as aggregating agents, and also have measured the secretion of platelet ATP simultaneously. Although the aggregometry results were similar, recordings obtained by the electrical method did not distinguish two waves of platelet aggregation or correlate with secretion as well as recordings obtained by the optical method. When PGI/sub 2/ (prostacyclin) or PGE/sub 1/ (prostaglandin E/sub 1/) was added to the PRP, both the rate and extent of the increase in light transmittance were inhibited, but the main effect on the increase in impedance was a decrease in its rate and not in its extent. Increases in impedance and secretion of ATP were also measured in whole blood after the platelets had been labeled with a /sup 125/I-containing antibody specific for platelet surface glycoproteins. It appeared that the increases in impedance lagged several minutes behind the formation of platelet aggregates and the secretion of platelet ATP.

  1. In vitro effects of ethanol on the pathways of platelet aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Rand, M.L.; Kinlough-Rathbone, R.L.; Packham, M.A.; Mustard, J.F.


    Ethanol is reported to inhibit platelet aggregation in vivo and in vitro, but the mechanisms of its action on stimulus-response coupling in platelets is unknown. Platelet aggregation to thrombin occurs through at least three pathways: released ADP; thromboxane A/sub 2/ (TXA/sub 2/); and a third pathway(s). Aggregation of rabbit platelets in citrated platelet-rich plasma (PRP) or washed suspensions to ADP (0.5-10 was not affected by ethanol, at concentrations up to 5 mg/ml (lethal). Primary ADP-induced (5 aggregation of human platelets in PRP was also unaffected by ethanol, but secondary aggregation and release of /sup 14/C-serotonin, due to TXA/sub 2/ formation, was inhibited by ethanol (2 and 4 mg/ml). Since arachidonate (AA)-induced (25-250 aggregation and release by washed rabbit platelets was unaltered by ethanol, it may inhibit mobilization of AA from platelet membrane phospholipids. Ethanol (2-4 mg/ml) inhibited rabbit platelet aggregation and release to low concentrations of thrombin (< 10 mU/ml) or collagen, and also inhibited aggregation and release of aspirin-treated (500 M) rabbit platelets (that cannot form TXA/sub 2/) to low concentrations of thrombin (< 10 mU/ml). Thus, ethanol does not inhibit the mobilization of AA, and partially inhibits the third pathway(s) of platelet aggregation.

  2. Systemic platelet dysfunction is the result of local dysregulated coagulation and platelet activation in the brain in a rat model of isolated traumatic brain injury. (United States)

    Ploplis, Victoria A; Donahue, Deborah L; Sandoval-Cooper, Mayra J; MorenoCaffaro, Maria; Sheets, Patrick; Thomas, Scott G; Walsh, Mark; Castellino, Francis J


    Coagulopathy after severe traumatic brain injury (TBI) has been extensively reported. Clinical studies have identified a strong relationship between diminished platelet-rich thrombus formation, responsiveness to adenosine diphosphate agonism, and severity of TBI. The mechanisms that lead to platelet dysfunction in the acute response to TBI are poorly understood. The development of a rodent model of TBI that mimics the coagulopathy observed clinically has recently been reported. Using immunohistochemical techniques and thromboelastography platelet mapping, the current study demonstrated that the expression of coagulation (tissue factor and fibrin) and platelet activation (P-selectin) markers in the injured brain paralleled the alteration in systemic platelet responsiveness to the agonists, adenosine diphosphate and arachodonic acid. Results of this study demonstrate that local procoagulant changes in the injured brain have profound effects on systemic platelet function.

  3. Arthroscopic meniscal allograft transplantation without bone plugs. (United States)

    Alentorn-Geli, Eduard; Seijas Vázquez, Roberto; García Balletbó, Montserrat; Álvarez Díaz, Pedro; Steinbacher, Gilbert; Cuscó Segarra, Xavier; Rius Vilarrubia, Marta; Cugat Bertomeu, Ramón


    Partial or total meniscectomy are common procedures performed at Orthopedic Surgery departments. Despite providing a great relief of pain, it has been related to early onset knee osteoarthritis. Meniscal allograft transplantation has been proposed as an alternative to meniscectomy. The purposes of this study were to describe an arthroscopic meniscal allograft transplantation without bone plugs technique and to report the preliminary results. All meniscal allograft transplantations performed between 2001 and 2006 were approached for eligibility, and a total of 35 patients (involving 37 menisci) were finally engaged in the study. Patients were excluded if they had ipsilateral knee ligament reconstruction or cartilage repair surgery before meniscal transplantation or other knee surgeries after the meniscal transplantation. Scores on Lysholm, Subjective IKDC Form, and Visual Analogue Scale (VAS) scale for pain were obtained at a mean follow-up of 38.6 months and compared to pre-operative data. Data on chondral lesions were obtained during the arthroscopic procedure and through imaging (radiographs and MRI) studies pre-operatively. Two graft failures out of 59 transplants (3.4%) were found. Daily life accidents were responsible for all graft failures. Significant improvements for Lysholm, Subjective IKDC Form, and VAS for pain scores following the meniscal allograft transplantation were found (P lesion, there was no significant interactions for Lysholm (n.s.), Subjective IKDC Form (n.s.), and VAS for pain scores (n.s.). This study demonstrated that an arthroscopic meniscal allograft transplantation without bone plugs improved knee function and symptoms after a total meniscectomy. Improvements were observed independently of the degree of chondral lesion.

  4. A mathematical model for in vitro coagulation of blood: role of platelet count and inhibition

    Indian Academy of Sciences (India)



    A mechanistic model including the role of platelets is proposed for clot formation and growth in plasma in vitro. Initiation of clot formation is by the addition of tissue factor, and initiation via the intrinsic pathway is neglected. Activation of zymogens follows the extrinsic pathway cascade and reactions on platelet membranes are included. Platelet activation occurs due to thrombin and also due to other activated platelets.Inhibition of the active clotting factors is by ATIII and TFPI, whereas inhibition due to APC is not relevant in the conditions modeled. The model predictions matched existing data for thrombin production in synthetic plasma. The model predicts that inhibition of platelet-driven activation of platelets has a major effect on concentration of activated platelets in PRP, normal plasma and PPP. Inhibition of platelet activation by (other activated) platelets significantly delays thrombin production in PRP and normal plasma as compared to that by thrombin. Further, sensitivity analysis shows that the model is most sensitive to the activation of platelet membrane-bound factor X by the intrinsic tenase complex.

  5. Strategies for Controlling Plug Loads. A Tool for Reducing Plug Loads in Commercial Buildings

    Energy Technology Data Exchange (ETDEWEB)

    Torcellini, Paul [National Renewable Energy Lab. (NREL), Golden, CO (United States); Bonnema, Eric [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sheppy, Michael [National Renewable Energy Lab. (NREL), Golden, CO (United States); Pless, Shanti [National Renewable Energy Lab. (NREL), Golden, CO (United States)


    Plug loads are often not considered as part of the energy savings measures in Commercial Buildings; however, they can account for up to 50% of the energy used in the building. These loads are numerous and often scattered throughout a building. Some of these loads are purchased by the owner and some designed into the building or the tenant finishes for a space. This document provides a strategy and a tool for minimizing these loads.

  6. Platelet immune complex interaction in pathogenesis of Kawasaki disease and childhood polyarteritis.


    Levin, M; Holland, P C; Nokes, T J; Novelli, V; Mola, M; Levinsky, R J; Dillon, M J; Barratt, T M; Marshall, W C


    The role of platelets in the pathogenesis of vasculitis and the formation of coronary artery aneurysms was studied in 19 children with Kawasaki disease and five with polyarteritis. All patients with Kawasaki disease developed thrombocytosis in the third week of illness. The peak platelet count was significantly correlated (p less than 0.005) with the subsequent development of coronary artery aneurysms. The rise in platelet count was associated with the appearance in the circulation of a facto...

  7. Vascular endothelium and platelet preparations for the prediction of xenobiotic effects on the vascular system. (United States)

    Togna, G; Togna, A R; Caprino, L


    Platelets and vascular cells play a fundamental role in the pathogenesis of cardiovascular diseases including thrombus formation and atherosclerotic phenomena. Preparations of platelets and aortic rings have been developed to study the potential of xenobiotics to produce evidence of vascular toxicity in vitro. The xenobiotics cadmium and mercury which exert vascular toxicity in vivo, modify platelet and endothelial-cell reactivity in these in vitro systems.

  8. The effect of platelet releasate on wound healing in animal models. (United States)

    Ksander, G A; Sawamura, S J; Ogawa, Y; Sundsmo, J; McPherson, J M


    The alpha granules of platelets contain growth factors that are important in wound healing. We found that a major effect of thrombin-induced human platelet releasates in animal models of wound healing is to enhance the development of granulation tissue and new connective tissue matrix. These studies provide further evidence that platelet-derived protein factors may be useful in treating full-thickness dermal wounds by increasing the rate of granulation tissue formation.

  9. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice


    Deppermann, Carsten; Cherpokova, Deya; Nurden, Paquita; Schulz, Jan-Niklas; Thielmann, Ina; Kraft, Peter; Vögtle, Timo; Kleinschnitz, Christoph; Dütting, Sebastian; Krohne, Georg; Eming, Sabine A.; Nurden, Alan T; Eckes, Beate; Stoll, Guido; Stegner, David


    Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, α-granules, release proteins that participate in thrombus formation and hemostasis. Proteins stored in α-granules are also thought to play a role in inflammation and wound healing, but their functional significance in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet syndrome (GPS), a rare bleeding disorder ch...

  10. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan


    Liu, Zhi-Jian; Hoffmeister, Karin M.; Hu, Zhongbo; Mager, Donald E.; Ait-Oudhia, Sihem; Debrincat, Marlyse A.; Pleines, Irina; Josefsson, Emma C.; Benjamin T Kile; Italiano, Joseph; Ramsey, Haley; Grozovsky, Renata; Veng-Pedersen, Peter; Chavda, Chaitanya; Sola-Visner, Martha


    Rapid growth and rising platelet counts result in a significant expansion of platelet mass during neonatal life.The rise in platelet counts is mediated by a prolongation in the neonatal platelet lifespan.

  11. Drug effects on platelet adherence to collagen and damaged vessel walls. (United States)

    Packham, M A; Cazenave, J P; Kinlough-Rathbone, R L; Mustard, J F


    The interaction of platelets with damaged vessel walls leads to the formation of platelet-fibrin thrombi and may also contribute to the development of atherosclerotic lesions because platelets adherent to exposed collagen release a mitogen that stimulates smooth muscle cell proliferation. The first step in thrombus formation, platelet adherence to an injured vessel wall, can be studied quantitatively by the use of platelets labeled with 51chromium. In these investigations, rabbit aortas were damaged by passage of a balloon catheter and segments of the aortas were everted on probes that were rotated in platelet suspensions. Collagen-coated glass cylinders were also used. Adherence was measured in a medium containing approximately physiologic concentrations of calcium, magnesium, protein and red blood cells. Conditions of testing influence the effect of non-steroidal anti-inflammatory drugs, sulfinpyrazone, and dipyridamole on platelet adherence. Aspirin and sulfinpyrazone were not inhibitory when tested in a medium with a 40% hematocrit; this indicates that products formed by platelets from arachidonate probably do not play a major part in the adherence of the first layer of platelets to the surface, although they may be involved in thrombus formation. Indomethacin, dipyridamole, prostaglandin E1, methylprednisolone and penicillin G and related antibiotics did inhibit platelet adherence although the concentrations required were higher than would likely be achieved in vivo upon administration to human patients. None of the non-steroidal anti-inflammatory drugs inhibited the release of granule contents from adherent platelets. Pretreatment of the damaged vessel wall with aspirin increased platelet adherence, presumably because it prevented the formation of PGI2 by the vessel wall. Platelet adherence to undamaged or damaged vessel walls was enhanced by prior exposure of the wall to thrombin. Platelet reactions with aggregating agents and platelet survival can be

  12. The Anal Fistula Plug versus the mucosal advancement flap for the treatment of Anorectal Fistula (PLUG trial

    Directory of Open Access Journals (Sweden)

    Janssen Lucas WM


    Full Text Available Abstract Background Low transsphincteric fistulas less than 1/3 of the sphincter complex are easy to treat by fistulotomy with a high success rate. High transsphincteric fistulas remain a surgical challenge. Various surgical procedures are available, but recurrence rates of these techniques are disappointingly high. The mucosal flap advancement is considered the gold standard for the treatment of high perianal fistula of cryptoglandular origin by most colorectal surgeons. In the literature a recurrence rate between 0 and 63% is reported for the mucosal flap advancement. Recently Armstrong and colleagues reported on a new biologic anal fistula plug, a bioabsorbable xenograft made of lyophilized porcine intestinal submucosa. Their prospective series of 15 patients with high perianal fistula treated with the anal fistula plug showed promising results. The anal fistula plug trial is designed to compare the anal fistula plug with the mucosal flap advancement in the treatment of high perianal fistula in terms of success rate, continence, postoperative pain, and quality of life. Methods/design The PLUG trial is a randomized controlled multicenter trial. Sixty patients with high perianal fistulas of cryptoglandular origin will be randomized to either the fistula plug or the mucosal advancement flap. Study parameters will be anorectal fistula closure-rate, continence, post-operative pain, and quality of life. Patients will be followed-up at two weeks, four weeks, and 16 weeks. At the final follow-up closure rate is determined by clinical examination by a surgeon blinded for the intervention. Discussion Before broadly implementing the anal fistula plug results of randomized trials using the plug should be awaited. This randomized controlled trial comparing the anal fistula plug and the mucosal advancement flap should provide evidence regarding the effectiveness of the anal fistula plug in the treatment of high perianal fistulas. Trial registration ISRCTN


    Directory of Open Access Journals (Sweden)

    Sheila K


    Full Text Available latelets play a vital role in haemostasis . Antenatal patients with platelet function disorders should be managed in tertiary care centres that are well equipped to tackle any obstetric haemorrhage that can ensue during labour and delivery . Primi gravida was admitted for safe confinement . She had been evaluated earlier for complaints of multiple episodes of mucosal bleeding . On evaluation she had nor mal platelet counts and coagulation factor assay was normal . Platelet aggregometry revealed mild disorder of platelet aggregation . She was planned for induction of labour after arranging enough blood and blood products . She got into active labour and was p ut on syntocinon augmentation . She had emergency Caesarean section for foetal distress . Oxytocics were given proactively . Intraoperatively platelet transfusions and tranexamic acid infusion were given . Complete haemostasis was achieved . She had an uneventf ul postoperative period . Patients with functional platelet disorders can be successfully managed with local application of antifibrinolytic agents like tranexamic acid , in case of minor bleeds . Platelet transfusions are very effective in tackling major ble eds , especially during surgeries and for obstetric indications . If a patient has the history of clinically significant bleeding suggestive of platelet dysfunction , appropriate platelet function tests should be obtained so that the risk of bleeding can be adequately assessed and therapy chosen more rationally . . In obstetric practice the response of such patients to platelet transfusions has been excellent

  14. Formats

    Directory of Open Access Journals (Sweden)

    Gehmann, Ulrich


    Full Text Available In the following, a new conceptual framework for investigating nowadays’ “technical” phenomena shall be introduced, that of formats. The thesis is that processes of formatting account for our recent conditions of life, and will do so in the very next future. It are processes whose foundations have been laid in modernity and which will further unfold for the time being. These processes are embedded in the format of the value chain, a circumstance making them resilient to change. In addition, they are resilient in themselves since forming interconnected systems of reciprocal causal circuits.Which leads to an overall situation that our entire “Lebenswelt” became formatted to an extent we don’t fully realize, even influencing our very percep-tion of it.

  15. Effects of hormones on platelet aggregation. (United States)

    Farré, Antonio López; Modrego, Javier; Zamorano-León, José J


    Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

  16. Platelet aggregation secondary to coronary obstruction. (United States)

    Moore, S


    From many observations made at autopsy it is apparent that thrombosis in a coronary artery is usually, if not always, associated with rupture of an atheromatous plaque. The sequelae of such rupture include hemorrhage into the plaque with further narrowing of the lumen, formation of an occlusive thrombus or of a non-occlusive thrombus. A developing thrombus in an artery undergoes fragmentation with showering of the distal microcirculation by aggregates of platelets possibly with some admixture of fibrin. In many cases of sudden cardiac death associated with severe atherosclerotic stenosis of the coronary vessels, an occlusive thrombus is not found and the myocardium shows no morphological lesion or else focal patchy early damage in the subendocardial region. One possible mechanism that might explain these findings is microembolism from mural nonobstructing coronary thrombus. Such a mechanism is well established in transient ischemia of the brain and retina related to ulcerated atheroma of the internal carotid artery. Experimental observations indicate that platelet aggregates in the myocardial circulation cause arrhythmias, sudden death, vasculitis, and myocardial ischemic damage. Induction of an occlusive coronary artery thrombus is associated with development of an infarct involving the full thickness of the myocardium. A nonocclusive thrombus is associated with either no myocardial damage or focal subendocardial ischemic injury. It is possible that further aggregation of platelets may facilitate the extension of infarction subsequent to an occlusive event, although there is little evidence on this point. A number of clinical studies show increased platelet reactivity to agents causing aggregation, such as norepinephrine or collagen, in subjects experiencing thromboembolic episodes. It seems unlikely, however, that in vitro tests of platelet function can identify or predict clinical arterial thrombotic disease, although studies of platelet survival and turnover

  17. Differential inhibitory action of apixaban on platelet and fibrin components of forming thrombi: Studies with circulating blood and in a platelet-based model of thrombin generation. (United States)

    Pujadas-Mestres, Lluis; Lopez-Vilchez, Irene; Arellano-Rodrigo, Eduardo; Reverter, Joan Carles; Lopez-Farre, Antonio; Diaz-Ricart, Maribel; Badimon, Juan Jose; Escolar, Gines


    Mechanisms of action of direct oral anticoagulants (DOAC) suggest a potential therapeutic use in the prevention of thrombotic complications in arterial territories. However, effects of DOACs on platelet activation and aggregation have not been explored in detail. We have investigated the effects of apixaban on platelet and fibrin components of thrombus formation under static and flow conditions. We assessed the effects of apixaban (10, 40 and 160 ng/mL) on: 1) platelet deposition and fibrin formation onto a thrombogenic surface, with blood circulating at arterial shear-rates; 2) viscoelastic properties of forming clots, and 3) thrombin generation in a cell-model of coagulation primed by platelets. In studies with flowing blood, only the highest concentration of apixaban, equivalent to the therapeutic Cmax, was capable to significantly reduce thrombus formation, fibrin association and platelet-aggregate formation. Apixaban significantly prolonged thromboelastometry parameters, but did not affect clot firmness. Interestingly, results in a platelet-based model of thrombin generation under more static conditions, revealed a dose dependent persistent inhibitory action by apixaban, with concentrations 4 to 16 times below the therapeutic Cmax significantly prolonging kinetic parameters and reducing the total amount of thrombin generated. Our studies demonstrate the critical impact of rheological conditions on the antithrombotic effects of apixaban. Studies under flow conditions combined with modified thrombin generation assays could help discriminating concentrations of apixaban that prevent excessive platelet accumulation, from those that deeply impair fibrin formation and may unnecessarily compromise hemostasis.

  18. Calcium Sulfate and Platelet-Rich Plasma make a novel osteoinductive biomaterial for bone regeneration

    Directory of Open Access Journals (Sweden)

    Intini Francesco E


    Full Text Available Abstract Background With the present study we introduce a novel and simple biomaterial able to induce regeneration of bone. We theorized that nourishing a bone defect with calcium and with a large amount of activated platelets may initiate a series of biological processes that culminate in bone regeneration. Thus, we engineered CS-Platelet, a biomaterial based on the combination of Calcium Sulfate and Platelet-Rich Plasma in which Calcium Sulfate also acts as an activator of the platelets, therefore avoiding the need to activate the platelets with an agonist. Methods First, we tested CS-Platelet in heterotopic (muscle and orthotopic (bone bone regeneration bioassays. We then utilized CS-Platelet in a variety of dental and craniofacial clinical cases, where regeneration of bone was needed. Results The heterotopic bioassay showed formation of bone within the muscular tissue at the site of the implantation of CS-Platelet. Results of a quantitative orthotopic bioassay based on the rat calvaria critical size defect showed that only CS-Platelet and recombinant human BMP2 were able to induce a significant regeneration of bone. A non-human primate orthotopic bioassay also showed that CS-Platelet is completely resorbable. In all human clinical cases where CS-Platelet was used, a complete bone repair was achieved. Conclusion This study showed that CS-Platelet is a novel biomaterial able to induce formation of bone in heterotopic and orthotopic sites, in orthotopic critical size bone defects, and in various clinical situations. The discovery of CS-Platelet may represent a cost-effective breakthrough in bone regenerative therapy and an alternative or an adjuvant to the current treatments.

  19. W-plug via electromigration in CMOS process

    Institute of Scientific and Technical Information of China (English)

    Zhao Wenbin; Chen Haifeng; Xiao Zhiqiang; Li Leilei; Yu Zongguang


    We analyze the failure mechanism of W-plug via electromigration made in a 0.5-μm CMOS SPTM process. Failure occurs at the top or bottom of a W-plug via. We design a series of via chains, whose size ranges from 0.35 to 0.55 μm. The structure for the via electromigration test is a long via chain, and the layer in the via is Ti/TiN/W/TiN. Using a self-heated resistor to raise the temperature of the via chain allows the structure to be stressed at lower current densities, which does not cause significant joule heating in the plugs. This reduces the interaction between the plug and the plug contact resistance and the time-to-failure for the via chain. The lifetime of a W-plug via electromigration is on the order of 3 × 107 s, i.e., far below the lifetime of metal electromigration. The study on W-plug via electromigraion in this paper is beneficial for wafer level reliability monitoring of the ultra-deep submicron CMOS multilayer metal interconnect process.

  20. Platelet aggregation following trauma

    DEFF Research Database (Denmark)

    Windeløv, Nis A; Sørensen, Anne M; Perner, Anders


    We aimed to elucidate platelet function in trauma patients, as it is pivotal for hemostasis yet remains scarcely investigated in this population. We conducted a prospective observational study of platelet aggregation capacity in 213 adult trauma patients on admission to an emergency department (ED......). Inclusion criteria were trauma team activation and arterial cannula insertion on arrival. Blood samples were analyzed by multiple electrode aggregometry initiated by thrombin receptor agonist peptide 6 (TRAP) or collagen using a Multiplate device. Blood was sampled median 65 min after injury; median injury...... severity score (ISS) was 17; 14 (7%) patients received 10 or more units of red blood cells in the ED (massive transfusion); 24 (11%) patients died within 28 days of trauma: 17 due to cerebral injuries, four due to exsanguination, and three from other causes. No significant association was found between...

  1. SDF-1α is a novel autocrine activator of platelets operating through its receptor CXCR4. (United States)

    Walsh, Tony G; Harper, Matthew T; Poole, Alastair W


    Platelets store and secrete the chemokine stromal cell-derived factor (SDF)-1α upon platelet activation, but the ability of platelet-derived SDF-1α to signal in an autocrine/paracrine manner mediating functional platelet responses relevant to thrombosis and haemostasis is unknown. We sought to explore the role of platelet-derived SDF-1α and its receptors, CXCR4 and CXCR7 in facilitating platelet activation and determine the mechanism facilitating SDF-1α-mediated regulation of platelet function. Using human washed platelets, CXCR4 inhibition, but not CXCR7 blockade significantly abrogated collagen-mediated platelet aggregation, dense granule secretion and thromboxane (Tx) A2 production. Time-dependent release of SDF-1α from collagen-activated platelets supports a functional role for SDF-1α in this regard. Using an in vitro whole blood perfusion assay, collagen-induced thrombus formation was substantially reduced with CXCR4 inhibition. In washed platelets, recombinant SDF-1α in the range of 20-100 ng/mL(-1) could significantly enhance platelet aggregation responses to a threshold concentration of collagen. These enhancements were completely dependent on CXCR4, but not CXCR7, which triggered TxA2 production and dense granule secretion. Rises in cAMP were significantly blunted by SDF-1α, which could also enhance collagen-mediated Ca2+ mobilisation, both of which were mediated by CXCR4. This potentiating effect of SDF-1α primarily required TxA2 signalling acting upstream of dense granule secretion, whereas blockade of ADP signalling could only partially attenuate SDF-1α-induced platelet activation. Therefore, this study supports a potentially novel autocrine/paracrine role for platelet-derived SDF-1α during thrombosis and haemostasis, through a predominantly TxA2-dependent and ADP-independent pathway.

  2. Delphinidin, a dietary anthocyanidin, inhibits platelet-derived growth factor ligand/receptor (PDGF/PDGFR) signaling. (United States)

    Lamy, Sylvie; Beaulieu, Edith; Labbé, David; Bédard, Valérie; Moghrabi, Albert; Barrette, Stéphane; Gingras, Denis; Béliveau, Richard


    Most cancers are dependent on the growth of tumor blood vessels and inhibition of tumor angiogenesis may thus provide an efficient strategy to retard or block tumor growth. Recently, tumor vascular targeting has expanded to include not only endothelial cells (ECs) but also smooth muscle cells (SMCs), which contribute to a mature and functional vasculature. We have reported previously that delphinidin, a major biologically active constituent of berries, inhibits the vascular endothelial growth factor-induced phosphorylation of vascular endothelial growth factor receptor-2 and blocks angiogenesis in vitro and in vivo. In the present study, we show that delphinidin also inhibits activation of the platelet-derived growth factor (PDGF)-BB receptor-beta [platelet-derived growth factor receptor-beta (PDGFR-beta)] in SMC and that this inhibition may contribute to its antitumor effect. The inhibitory effect of delphinidin on PDGFR-beta was very rapid and led to the inhibition of PDGF-BB-induced activation of extracellular signal-regulated kinase (ERK)-1/2 signaling and of the chemotactic motility of SMC, as well as the differentiation and stabilization of EC and SMC into capillary-like tubular structures in a three-dimensional coculture system. Using an anthocyan-rich extract of berries, we show that berry extracts were able to suppress the synergistic induction of vessel formation by basic fibroblast growth factor-2 and PDGF-BB in the mouse Matrigel plug assay. Oral administration of the berry extract also significantly retarded tumor growth in a lung carcinoma xenograft model. Taken together, these results provide new insight into the molecular mechanisms underlying the antiangiogenic activity of delphinidin that will be helpful for the development of dietary-based chemopreventive strategies.

  3. Mechanical and thermo-mechanical analyses of the tapered plug for plugging of deposition tunnels. A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Faelth, Billy (Clay Technology AB, Lund (Sweden)); Gatter, Patrik (Vattenfall Power Consultant AB, Stockholm (Sweden))


    This report presents results from a study that was carried out in order to examine the applicability of the tapered plug concept for plugging of deposition tunnels in the deep repository for spent nuclear fuel. The report presents results from mechanical and thermo-mechanical models of the tapered plug. The models were analyzed with 3DEC. The models included a portion of a deposition tunnel and its intersection with a main tunnel. In the deposition tunnel, a tapered concrete plug was installed. The plug was subjected to the combined load from the swelling backfill material and from pore pressure inside the deposition tunnel. The thermo-mechanical effects due to the heat generation in the spent fuel were also included in the analyses. Generic material parameter values for the concrete were used. The following items were studied: - Stresses and displacements in the plug. - Shear stresses and shear displacements in the rock-concrete interface. - Stress additions in the rock due to the loads. The sensitivity of the results to changes of constitutive models, to changes of the plug geometry and to pore water pressure in the rock-concrete interface was examined. The results indicate that the displacements in the plug will be within reasonable ranges but the stresses may locally be high enough that they exceed acceptable levels. However, they can be reduced by choice of advantageous plug geometry and by having a good rock-concrete bond. The results also show that the stress additions in the rock due to the thermal load may yield stresses that locally exceed the spalling strength of the rock. At most locations, however, the rock stresses will amount at lower levels. It was concluded that, with choice of an appropriate design, the tapered plug seems to be an applicable concept for plugging of deposition tunnels. It was also concluded that further studies of the tapered plug concept should use material properties parameter values for low-pH concrete. Further, they should also

  4. Kaempferol inhibits thrombosis and platelet activation. (United States)

    Choi, Jun-Hui; Park, Se-Eun; Kim, Sung-Jun; Kim, Seung


    The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin clot formation, blood clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, thrombosis, and coagulation in ICR (Imprinting Control Region) mice and SD (Sprague-Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (clotting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation. Moreover, kaempferol protected against thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboembolism models and an FeCl3-induced carotid arterial thrombus model. The ex vivo anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge.

  5. A Genre Classification Plug-in for Data Collection

    DEFF Research Database (Denmark)

    Lehn-Schiøler, Tue; Arenas-García, Jerónimo; Petersen, Kaare Brandt;


    This demonstration illustrates how the methods developed in the MIR community can be used to provide real-time feedback to music users. By creating a genre classifier plug-in for a popular media player we present users with relevant information as they play their songs. The plug-in can furthermor...... be used as a data collection platform. After informed consent from a selected set of users the plug-in will report on music consumption behavior back to a central server....

  6. Platelets in inflammation and immunity. (United States)

    Herter, J M; Rossaint, J; Zarbock, A


    The paradigm of platelets as mere mediators of hemostasis has long since been replaced by a dual role: hemostasis and inflammation. Now recognized as key players in innate and adaptive immune responses, platelets have the capacity to interact with almost all known immune cells. These platelet-immune cell interactions represent a hallmark of immunity, as they can potently enhance immune cell functions and, in some cases, even constitute a prerequisite for host defense mechanisms such as NETosis. In addition, recent studies have revealed a new role for platelets in immunity: They are ubiquitous sentinels and rapid first-line immune responders, as platelet-pathogen interactions within the vasculature appear to precede all other host defense mechanisms. Here, we discuss recent advances in our understanding of platelets as inflammatory cells, and provide an exemplary review of their role in acute inflammation.

  7. Estrogen, inflammation, and platelet phenotype. (United States)

    Miller, Virginia M; Jayachandran, Muthuvel; Hashimoto, Kazumori; Heit, John A; Owen, Whyte G


    Although exogenous estrogenic therapies increase the risk of thrombosis, the effects of estrogen on formed elements of blood are uncertain. This article examines the genomic and nongenomic actions of estrogen on platelet phenotype that may contribute to increased thrombotic risk. To determine aggregation, secretion, protein expression, and thrombin generation, platelets were collected from experimental animals of varying hormonal status and from women enrolled in the Kronos Early Estrogen Prevention Study. Estrogen receptor beta predominates in circulating platelets. Estrogenic treatment in ovariectomized animals decreased platelet aggregation and adenosine triphosphate (ATP) secretion. However, acute exposure to 17beta-estradiol did not reverse decreases in platelet ATP secretion invoked by lipopolysaccharide. Thrombin generation was positively correlated to the number of circulating microvesicles expressing phosphatidylserine. Assessing the effect of estrogen treatments on blood platelets may lead to new ways of identifying women at risk for adverse thrombotic events with such therapies.

  8. Current Role of Platelet Glycoprotein Ⅱ b/Ⅲ a Receptor Inhibitors in Clinic-al Trials of Cardiovascular Diseases

    Institute of Scientific and Technical Information of China (English)

    SHEN Di


    @@Thrombosis formation on disrupted atherosclerotic plaque is the most common acuse of cardiovascular dis eases, in the pathophysiology, increased platelet reactiv ity is a descriptor of the risk of cardiovascular events in healthy persons and in patients with overt coronary artery disease. Regardless of the stimulus for activation platelet-platelet interation and thrombus formation is ul timately regulated through the GP Ⅱ b/Ⅲ a receptor complex

  9. Effects of platelet-poor plasma, platelet-rich plasma, and platelet-rich fibrin on healing of extraction sockets with buccal dehiscence in dogs. (United States)

    Hatakeyama, Ichiro; Marukawa, Eriko; Takahashi, Yukinobu; Omura, Ken


    Alveolar bone resorption generally occurs during healing after tooth extraction. This study aimed to evaluate the effects of platelet-poor plasma (PPP), platelet-rich plasma (PRP), and platelet-rich fibrin (PRF) on healing in a ridge-augmentation model of the canine socket with dehiscence of the buccal wall. The third mandibular premolars of 12 beagle dogs were extracted and a 3 mm buccal dehiscence from the alveolar crest to the buccal wall of the extraction socket was created. These sockets were then divided into four groups on the basis of the material used to fill the sockets: PPP, PRP, PRF, and control (no graft material) groups. Results were evaluated at 4 and 8 weeks after surgery. The ultrastructural morphology and constructs of each blood product were studied by a scanning electron microscope (SEM) or calculating concentrations of platelets, fibrinogen, platelet-derived growth factor, and transforming growth factor-β. A total of five microcomputed tomography images of specimens were selected for measurement, and the area occupied by the newly formed bone as well as the horizontal bone width were measured. Moreover, decalcified tissue specimens from each defect were analyzed histologically. The median area of new bone at 4 and 8 weeks and median horizontal bone width at 8 weeks were the highest in the PPP group. However, bone maturation in the PRF and the PRP groups was more progressed than that in the PPP and control groups. By SEM findings, the PRF group showed a more highly condensed fibrin fiber network that was regularly arranged when compared with the PPP and PRP groups. The growth factors released from platelets in PRP indicated higher concentrations than that in PRF. Under more severe conditions for bone formation, as in this experiment, the growth factors released from platelets had a negative effect on bone formation. This study showed that PPP is an effective material for the preservation of sockets with buccal dehiscence.

  10. Analysis of Reparative Activity of Platelet Lysate: Effect on Cell Monolayer Recovery In Vitro and Skin Wound Healing In Vivo. (United States)

    Sergeeva, N S; Shanskii, Ya D; Sviridova, I K; Karalkin, P A; Kirsanova, V A; Akhmedova, S A; Kaprin, A D


    Platelet lysate prepared from donor platelet concentrate and pooled according to a developed technique stimulates migration of multipotent mesenchymal stromal cells of the human adipose tissue and promotes healing of the monolayer defect in cultures of human fibroblasts and multipotent mesenchymal stromal cells in vitro in concentrations close those of fetal calf serum (5-10%). Lysate of platelets from platelet-rich rat blood plasma stimulated healing of the skin defect by promoting epithelialization and granulation tissue formation. The regenerative properties of platelet lysate in vivo increased with increasing its concentration.

  11. Complement Activation Alters Platelet Function (United States)


    Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet Function PRINCIPAL INVESTIGATOR: George Tsokos, M.D. CONTRACTING...Activation Alters Platelet Function 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0523 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) George Tsokos, M.D...a decreased level of disease. Further studies will expand upon these observations better outlining the function of platelets in the injury associated

  12. Where do the platelets go? A simulation study of fully resolved blood flow through aneurysmal vessels

    NARCIS (Netherlands)

    Mountrakis, L.; Lorenz, E.; Hoekstra, A.G.


    Despite the importance of platelets in the formation of a thrombus, their transport in complex flows has not yet been studied in detail. In this paper we simulated red blood cells and platelets to explore their transport behaviour in aneurysmal geometries. We considered two aneurysms with different

  13. Platelet effects on ovarian cancer (United States)

    Davis, Ashley; Afshar-Kharghan, Vahid; Sood, Anil K.


    Growing understanding of the role of thrombocytosis, high platelet turnover, and the presence of activated platelets in the circulation in cancer progression and metastasis has brought megakaryocytes into focus. Platelet biology is essential to hemostasis, vascular integrity, angiogenesis, inflammation, innate immunity, wound healing, and cancer biology. However, before megakaryocyte/platelet-directed therapies can be considered for clinical use, understanding of the mechanism and biology of paraneoplastic thrombocytosis in malignancy is required. Here, we provide an overview of the clinical implications, biological significance, and mechanisms of paraneoplastic thrombocytosis in the context of ovarian cancer. PMID:25023353

  14. Overview of platelet physiology and laboratory evaluation of platelet function. (United States)

    Rodgers, G M


    Appropriate laboratory testing for the platelet-type bleeding disorders hinges on an adequate assessment in the history and physical examination. Patients with histories and screening laboratory results consistent with coagulation disorders (hemophilia, disseminated intravascular coagulation) are not appropriate candidates for platelet function testing. In contrast, patients with a lifelong history of platelet-type bleeding symptoms and perhaps a positive family history of bleeding would be appropriate for testing. Figure 6 depicts one strategy to evaluate these patients. Platelet morphology can easily be evaluated to screen for two uncommon qualitative platelet disorders: Bernard-Soulier syndrome (associated with giant platelets) and gray platelet syndrome, a subtype of storage pool disorder in which platelet granulation is morphologically abnormal by light microscopy. If the bleeding disorder occurred later in life (no bleeding with surgery or trauma early in life), the focus should be on acquired disorders of platelet function. For those patients thought to have an inherited disorder, testing for vWD should be done initially because approximately 1% of the population has vWD. The complete vWD panel (factor VIII coagulant activity, vWf antigen, ristocetin cofactor activity) should be performed because many patients will have abnormalities of only one particular panel component. Patients diagnosed with vWD should be classified using multimeric analysis to identify the type 1 vWD patients likely to respond to DDAVP. If vWD studies are normal, platelet aggregation testing should be performed, ensuring that no antiplatelet medications have been ingested at least 1 week before testing. If platelet aggregation tests are normal and if suspicion for an inherited disorder remains high, vWD testing should be repeated. The evaluation of thrombocytopenia may require bone marrow examination to exclude primary hematologic disorders. If future studies with thrombopoietin assays

  15. Increased platelet activation in early symptomatic versus asymptomatic carotid stenosis and relationship with microembolic status: Results from the Platelets And Carotid Stenosis (PACS) Study.

    LENUS (Irish Health Repository)

    Kinsella, Ja


    -negative patients (2.8 vs. 2.3%; p=0.0085). DISCUSSION: Recently symptomatic carotid stenosis patients have higher platelet counts (potentially reflecting increased platelet production, mobilisation or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients. This article is protected by copyright. All rights reserved.

  16. SI Engine with repetitive NS spark plug (United States)

    Pancheshniy, Sergey; Nikipelov, Andrey; Anokhin, Eugeny; Starikovskiy, Andrey; Laplase Team; Mipt Team; Pu Team


    Now de-facto the only technology for fuel-air mixtures ignition in IC engines exists. It is a spark discharge of millisecond duration in a short discharge gap. The reason for such a small variety of methods of ignition initiation is very specific conditions of the engine operation. First, it is very high-pressure of fuel-air mixture - from 5-7 atmospheres in old-type engines and up to 40-50 atmospheres on the operating mode of HCCI. Second, it is a very wide range of variation of the oxidizer/fuel ratio in the mixture - from almost stoichiometric (0.8-0.9) at full load to very lean (φ = 0.3-0.5) mixtures at idle and/or economical cruising mode. Third, the high velocity of the gas in the combustion chamber (up to 30-50 m/s) resulting in a rapid compression of swirling inlet flow. The paper presents the results of tests of distributed spark ignition system powered by repetitive pulse nanosecond discharge. Dynamic pressure measurements show the increased pressure and frequency stability for nanosecond excitation in comparison with the standard spark plug. Excitation by single nanosecond high-voltage pulse and short train of pulses was examined. In all regimes the nanosecond pulsed excitation demonstrate a better performance.

  17. Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries

    Directory of Open Access Journals (Sweden)

    Conglei Li


    Full Text Available Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc., which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs, such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1. Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions.

  18. Collagen can selectively trigger a platelet secretory phenotype via glycoprotein VI.

    Directory of Open Access Journals (Sweden)

    Véronique Ollivier

    Full Text Available Platelets are not only central actors of hemostasis and thrombosis but also of other processes including inflammation, angiogenesis, and tissue regeneration. Accumulating evidence indicates that these "non classical" functions of platelets do not necessarily rely on their well-known ability to form thrombi upon activation. This suggests the existence of non-thrombotic alternative states of platelets activation. We investigated this possibility through dose-response analysis of thrombin- and collagen-induced changes in platelet phenotype, with regards to morphological and functional markers of platelet activation including shape change, aggregation, P-selectin and phosphatidylserine surface expression, integrin activation, and release of soluble factors. We show that collagen at low dose (0.25 µg/mL selectively triggers a platelet secretory phenotype characterized by the release of dense- and alpha granule-derived soluble factors without causing any of the other major platelet changes that usually accompany thrombus formation. Using a blocking antibody to glycoprotein VI (GPVI, we further show that this response is mediated by GPVI. Taken together, our results show that platelet activation goes beyond the mechanisms leading to platelet aggregation and also includes alternative platelet phenotypes that might contribute to their thrombus-independent functions.

  19. Platelet activation using electric pulse stimulation: growth factor profile and clinical implications. (United States)

    Torres, Andrew S; Caiafa, Antonio; Garner, Allen L; Klopman, Steve; LaPlante, Nicole; Morton, Christine; Conway, Kenneth; Michelson, Alan D; Frelinger, Andrew L; Neculaes, V Bogdan


    Autologous platelet gel therapy using platelet-rich plasma has emerged as a promising alternative for chronic wound healing, hemostasis, and wound infection control. A critical step for this therapeutic approach is platelet activation, typically performed using bovine thrombin (BT) and calcium chloride. However, exposure of humans to BT can stimulate antibody formation, potentially resulting in severe hemorrhagic or thrombotic complications. Electric pulse stimulation using nanosecond PEFs (pulse electric fields) is an alternative, nonbiochemical platelet activation method, thereby avoiding exposure to xenogeneic thrombin and associated risks. In this study, we identified specific requirements for a clinically relevant activator instrument by dynamically measuring current, voltage, and electric impedance for platelet-rich plasma samples. From these samples, we investigated the profile of growth factors released from human platelets with electric pulse stimulation versus BT, specifically platelet-derived growth factor, transforming growth factor β, and epidermal growth factor, using commercial enzyme-linked immunosorbent assay kits. Electric pulse stimulation triggers growth factor release from platelet α-granules at the same or higher level compared with BT. Electric pulse stimulation is a fast, inexpensive, easy-to-use platelet activation method for autologous platelet gel therapy.

  20. Abnormal whole blood thrombi in humans with inherited platelet receptor defects.

    Directory of Open Access Journals (Sweden)

    Francis J Castellino

    Full Text Available To delineate the critical features of platelets required for formation and stability of thrombi, thromboelastography and platelet aggregation measurements were employed on whole blood of normal patients and of those with Bernard-Soulier Syndrome (BSS and Glanzmann's Thrombasthenia (GT. We found that separation of platelet activation, as assessed by platelet aggregation, from that needed to form viscoelastic stable whole blood thrombi, occurred. In normal human blood, ristocetin and collagen aggregated platelets, but did not induce strong viscoelastic thrombi. However, ADP, arachidonic acid, thrombin, and protease-activated-receptor-1 and -4 agonists, stimulated both processes. During this study, we identified the genetic basis of a very rare double heterozygous GP1b deficiency in a BSS patient, along with a new homozygous GP1b inactivating mutation in another BSS patient. In BSS whole blood, ADP responsiveness, as measured by thrombus strength, was diminished, while ADP-induced platelet aggregation was normal. Further, the platelets of 3 additional GT patients showed very weak whole blood platelet aggregation toward the above agonists and provided whole blood thrombi of very low viscoelastic strength. These results indicate that measurements of platelet counts and platelet aggregability do not necessarily correlate with generation of stable thrombi, a potentially significant feature in patient clinical outcomes.

  1. Abnormal whole blood thrombi in humans with inherited platelet receptor defects. (United States)

    Castellino, Francis J; Liang, Zhong; Davis, Patrick K; Balsara, Rashna D; Musunuru, Harsha; Donahue, Deborah L; Smith, Denise L; Sandoval-Cooper, Mayra J; Ploplis, Victoria A; Walsh, Mark


    To delineate the critical features of platelets required for formation and stability of thrombi, thromboelastography and platelet aggregation measurements were employed on whole blood of normal patients and of those with Bernard-Soulier Syndrome (BSS) and Glanzmann's Thrombasthenia (GT). We found that separation of platelet activation, as assessed by platelet aggregation, from that needed to form viscoelastic stable whole blood thrombi, occurred. In normal human blood, ristocetin and collagen aggregated platelets, but did not induce strong viscoelastic thrombi. However, ADP, arachidonic acid, thrombin, and protease-activated-receptor-1 and -4 agonists, stimulated both processes. During this study, we identified the genetic basis of a very rare double heterozygous GP1b deficiency in a BSS patient, along with a new homozygous GP1b inactivating mutation in another BSS patient. In BSS whole blood, ADP responsiveness, as measured by thrombus strength, was diminished, while ADP-induced platelet aggregation was normal. Further, the platelets of 3 additional GT patients showed very weak whole blood platelet aggregation toward the above agonists and provided whole blood thrombi of very low viscoelastic strength. These results indicate that measurements of platelet counts and platelet aggregability do not necessarily correlate with generation of stable thrombi, a potentially significant feature in patient clinical outcomes.

  2. Effect of ascorbate on plasminogen activator inhibitor-1 expression and release from platelets and endothelial cells in an in-vitro model of sepsis. (United States)

    Swarbreck, Scott B; Secor, Dan; Ellis, Christopher G; Sharpe, Michael D; Wilson, John X; Tyml, Karel


    The microcirculation during sepsis fails due to capillary plugging involving microthrombosis. We demonstrated that intravenous injection of ascorbate reduces this plugging, but the mechanism of this beneficial effect remains unclear. We hypothesize that ascorbate inhibits the release of the antifibrinolytic plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and platelets during sepsis. Microvascular endothelial cells and platelets were isolated from mice. Cells were cultured and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα), or thrombin (agents of sepsis), with/without ascorbate for 1-24 h. PAI-1 mRNA was determined by quantitative PCR. PAI-1 protein release into the culture medium was measured by ELISA. In platelets, PAI-1 release was measured after LPS, TNFα, or thrombin stimulation, with/without ascorbate. In endothelial cells, LPS and TNFα increased PAI-1 mRNA after 6-24 h, but no increase in PAI-1 release was observed; ascorbate did not affect these responses. In platelets, thrombin, but not LPS or TNFα, increased PAI-1 release; ascorbate inhibited this increase at low extracellular pH. In unstimulated endothelial cells and platelets, PAI-1 is released into the extracellular space. Thrombin increases this release from platelets; ascorbate inhibits it pH-dependently. The data suggest that ascorbate promotes fibrinolysis in the microvasculature under acidotic conditions in sepsis.

  3. Interaction of human umbilical vein endothelial cells (HUVEC) with platelets in vitro: Influence of platelet concentration and reactivity. (United States)

    Krüger, A; Mrowietz, C; Lendlein, A; Jung, F


    Endothelialisation of polymer-based cardiovascular implants is one strategy to render biomaterials hemocompatible. The evaluation of the functionality and the confluence of an endothelial cell (EC) monolayer in vitro is therefore of crucial importance, because a non-functional or non-confluent EC monolayer can contribute to the failure of vascular grafts. Moreover, the comparison of different potential biomaterials regarding their ability to induce the formation of a functional confluent EC monolayer is of great value. Most of the currently reported in vitro studies focus on direct or indirect markers of EC behaviour. However, these studies still lack the final proof that the EC monolayer, which can be developed on polymers is confluent and functional. In this study, we investigated the suitability of an in vitro co-culture of human umbilical vein endothelial cells (HUVEC) with platelets to predict the functionality of an EC monolayer. The interaction of platelets with HUVEC was evaluated depending on the concentration of the platelets in the added plasma and of the reactivity of the platelets to pharmacological stimuli. For this purpose, HUVEC were seeded in a 24 well plate. After three days of cultivation, platelets were added to the HUVEC cell culture medium to final concentrations of 200, 2,000 or 20,000 platelets/μl (n = 7 each). The platelets were processed immediately after blood collection and added to the HUVEC culture after a 30 minutes resting period. As a first control, an EC monolayer just cultured with EC medium was used. As a second control EC supplemented with plasma without platelets were applied. The HUVEC monolayer was investigated microscopically after 1 hour of platelet exposition. The addition of thrombocytes to EC affected the EC adherence dependent on the initial cell seeding number of HUVEC, the platelet concentration and also on the reactivity of platelets added. In both controls no significant EC detachment was detected. The results

  4. An Increase in Mean Platelet Volume/Platelet Count Ratio Is Associated with Vascular Access Failure in Hemodialysis Patients (United States)

    Shin, Dong Ho; Rhee, So Yon; Jeon, Hee Jung; Park, Ji-Young; Kang, Shin-Wook; Oh, Jieun


    After stenosis of arteriovenous vascular access in hemodialysis patients, platelets play a crucial role in subsequent thrombus formation, leading to access failure. In a previous study, the mean platelet volume (MPV)/platelet count ratio, but not MPV alone, was shown to be an independent predictor of 4-year mortality after myocardial infarction. However, little is known about the potential influence of MPV/platelet count ratio on vascular access patency in hemodialysis patients. A total of 143 patients undergoing routine hemodialysis were recruited between January 2013 and February 2016. Vascular access failure (VAF) was defined as thrombosis or a decrease of greater than 50% of normal vessel diameter, requiring either surgical revision or percutaneous transluminal angioplasty. Cox proportional hazards model analysis ascertained that the change of MPV/platelet count ratio between baseline and 3 months [Δ(MPV/platelet count ratio)3mo-baseline] had prognostic value for VAF. Additionally, the changes of MPV/platelet count ratio over time were compared in patients with and without VAF by using linear mixed model analysis. Of the 143 patients, 38 (26.6%) were diagnosed with VAF. During a median follow-up of 26.9 months (interquartile range 13.0–36.0 months), Δ(MPV/platelet count ratio)3mo-baseline significantly increased in patients with VAF compared to that in patients without VAF [11.6 (6.3–19.0) vs. 0.8 (-1.8–4.0), P< 0.001]. In multivariate analysis, Δ(MPV/platelet ratio count)3mo-baseline was an independent predictor of VAF, after adjusting for age, sex, diabetes, hypertension, coronary artery disease, cerebrovascular disease, vascular access type, the presence of previous VAF, and antiplatelet drug use (hazard ratio, 1.15; 95% confidence interval, 1.10–1.21; P< 0.001). Moreover, a liner mixed model revealed that there was a significant increase of MPV/platelet count ratio over time in patients with VAF compared to those without VAF (P< 0.001). An

  5. Development of a Special Application Coiled Tubing Applied Plug for Geothermal Well Casing Remediation

    Energy Technology Data Exchange (ETDEWEB)



    Casing deformation in producing geothermal wells is a common problem in many geothermal fields, mainly due to the active geologic formations where these wells are typically located. Repairs to deformed well casings are necessary to keep the wells in production and to occasionally enter a well for approved plugging and abandonment procedures. The costly alternative to casing remediation is to drill a new well to maintain production and/or drill a well to intersect the old well casing below the deformation for abandonment purposes. The U.S. Department of Energy and the Geothermal Drilling Organization sponsored research and development work at Sandia National Laboratories in an effort to reduce these casing remediation expenditures. Sandia, in cooperation with Halliburton Energy Services, developed a low cost, bridge-plug-type, packer for use in casing remediation work in geothermal well environments. This report documents the development and testing of this commercially available petal-basket packer called the Special Application Coiled Tubing Applied Plug (SACTAP).

  6. Engaging Tenants in Reducing Plug Load Energy Use

    Energy Technology Data Exchange (ETDEWEB)

    Schantz, Marta; Langner, Rois


    Plug and Process Loads (PPLs) account for an increasingly large percentage of commercial building energy use in the U.S. due to the rising number of energy intensive plug-in devices. In addition, buildings are becoming more and more efficient and plug load energy use has become an increasingly pertinent component to achieving aggressive energy targets and netzero energy status. For multi-tenant buildings, controlling plug loads in tenant spaces can be a significant challenge. Luckily, there are a number of PPL reduction strategies, best practices, and lessons learned from numerous commercial real estate and higher education leaders who have successfully engaged building occupants and tenants in reducing PPL energy use. This paper provides actionable PPL reduction strategies and best practices that building owners and managers can immediately apply to their own buildings.

  7. Rotary plug device for use in LMFBR type reactors

    Energy Technology Data Exchange (ETDEWEB)

    Azuma, Kazuhiko; Imayoshi, Sho.


    Purpose: To prevent adhesion of sodium in the rotational gap of a rotational plug. Constitution: One of the walls of a cylindrical gap formed between the outer circumference of a small rotary plug and a large rotary plug that constitute a double rotary plug is cooled to lower than the sodium coagulation temperature, while a stater of a linear motor in a cylindrical shape and wound with linear coils around the iron core is attached to the inside of the other of the walls. Then, one of the walls of the gap to which sodium adheres is cooled to less than sodium coagulation temperature, so that sodium is or tends to be deposited to the wall. Then, eddy currents are resulted to sodium by the current supplied to the stater of the linear motor attached to the other of the walls, to produce thrusting force. Sodium on the wall surface is scraped off by this. (Yoshihara, H.).

  8. Application of Inductive Monitoring System to Plug Load Anomaly Detection (United States)

    National Aeronautics and Space Administration — NASA Ames Research Center’s Sustainability Base is a new 50,000 sq. ft. LEED Platinum office building. Plug loads are expected to account for a significant portion...

  9. Waste isolation pilot plant (WIPP) borehole plugging program description

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, C.L.; Hunter, T.O.


    The tests and experiments described attempt to provide a mix of borehole (with limited access) and in-mine (with relatively unlimited access) environments in which assessment of the various issues involved can be undertaken. The Bell Canyon Test provides the opportunity to instrument and analyze a plug in a high pressure region. The Shallow Hole Test permits application of best techniques for plugging and then access to both the top and bottom of the plug for further analysis. The Diagnostic Test Hole permits recovery of bench scale size samples for analysis and establishes an in-borehole laboratory in which to conduct testing and analysis in all strata from the surface into the salt horizon. The additional in mine experiments provide the opportunity to investigate in more detail specific effects on plugs in the salt region and allows evaluation of instrumentation systems.

  10. Mechanical Properties of Plug Welds after Micro-Jet Cooling

    Directory of Open Access Journals (Sweden)

    Hadryś D.


    Full Text Available New technology of micro-jet welding could be regarded as a new way to improve mechanical properties of plug welds. The main purpose of that paper was analyzing of mechanical properties of plug welds made by MIG welding method with micro-jet cooling. The main way for it was comparison of plug welds made by MIG welding method with micro-jet cooling and plug welds made by ordinary MIG welding method. It is interesting for steel because higher amount of acicular ferrite (AF in weld metal deposit (WMD is obtained in MIG welding method with micro-jet cooling in relation to ordinary MIG welding method. This article presents the influence of the cooling medium and the number of micro-jet streams on mechanical properties of the welded joint. Mechanical properties were described by force which is necessary to destroy weld joint.

  11. Platelet Concentrates: Past, Present and Future



    Platelets play a crucial role in hemostasis and wound healing, platelet growth factors are well known source of healing cytokines. Numerous techniques of autologous platelet concentrates have been developed and applied in oral and maxillofacial surgery. This review describes the evolution of the first and second generation of platelet concentrates (platelet rich plasma and platelet rich fibrin respectively) from their fore runner-fibrin sealants.

  12. Studies on megakaryopoiesis and platelet function


    Meinders, M.


    Platelets are blood circulating specialized subcellular fragments, which are produced by megakaryocytes. Platelets are essential for hemostasis and wound healing but also play a role in non-hemostatic processes such as the immune response or cancer metastasis. Considering the immediate precursors of platelets, normal megakaryocyte development is essential for normal platelet function. Although much is known about platelet development, some aspects of platelet production remain poorly understo...

  13. Biologically formed calcium carbonate : a durable plugging agent for enhanced oil recovery

    Energy Technology Data Exchange (ETDEWEB)

    Nemati, M.; Voordouw, G. [Calgary Univ., AB (Canada)


    Waterflooding is a common enhanced oil recovery method in which water is injected into an oil reservoir. The flow is diverted into high permeability zones from which oil has already been recovered during primary production. The increased permeability variation decreases volumetric sweep efficiency of injected water. Cross flow complicates this problem by allowing flow between contrasting layers. This results in a ratio of produced water to oil that is much too high. The use of calcium carbonate (CaCO{sub 3}) and silica may be an effective method for selective plugging of reservoirs. The controlled biological formation of CaCO{sub 3} depends on the decomposition of urea to carbonate and ammonium ions by the catalytic action of urease enzyme. This study shows that biological formation of CaCO{sub 3} could be induced successfully using a bacterium with urease producing activity or urease enzyme. It is shown that the yield of enzymatically produced CaCO{sub 3} is substantially higher than when bacterially produced because the tolerable level of urea for bacteria is lower than the concentration of urea that participates in the enzymatic reaction. Plugging studies in unconsolidated porous media have shown that in situ formation of CaCO{sub 3} may decrease the permeability of porous media. The extent of plugging depends on the enzyme and reactant concentration. The extent of enzymatically produced CaCO{sub 3} increases with higher enzyme concentrations as well as with higher temperature. In situ formation of CaCO{sub 3} could result in a major decrease in permeability. 4 refs., 1 tab., 1 fig.

  14. Storage pool diseases illuminate platelet dense granule biogenesis. (United States)

    Ambrosio, Andrea L; Di Pietro, Santiago M


    Platelet dense granules (DGs) are membrane bound compartments that store polyphosphate and small molecules such as ADP, ATP, Ca(2+), and serotonin. The release of DG contents plays a central role in platelet aggregation to form a hemostatic plug. Accordingly, congenital deficiencies in the biogenesis of platelet DGs underlie human genetic disorders that cause storage pool disease and manifest with prolonged bleeding. DGs belong to a family of lysosome-related organelles, which also includes melanosomes, the compartments where the melanin pigments are synthesized. These organelles share several characteristics including an acidic lumen and, at least in part, the molecular machinery involved in their biogenesis. As a result, many genes affect both DG and melanosome biogenesis and the corresponding patients present not only with bleeding but also with oculocutaneous albinism. The identification and characterization of such genes has been instrumental in dissecting the pathways responsible for organelle biogenesis. Because the study of melanosome biogenesis has advanced more rapidly, this knowledge has been extrapolated to explain how DGs are produced. However, some progress has recently been made in studying platelet DG biogenesis directly in megakaryocytes and megakaryocytoid cells. DGs originate from an endosomal intermediate compartment, the multivesicular body. Maturation and differentiation into a DG begins when newly synthesized DG-specific proteins are delivered from early/recycling endosomal compartments. The machinery that orchestrates this vesicular trafficking is composed of a combination of both ubiquitous and cell type-specific proteins. Here, we review the current knowledge on DG biogenesis. In particular, we focus on the individual human and murine genes encoding the molecular machinery involved in this process and how their deficiencies result in disease.

  15. Plasminogen associates with phosphatidylserine-exposing platelets and contributes to thrombus lysis under flow. (United States)

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


    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.

  16. Extract of feverfew inhibits interactions of human platelets with collagen substrates

    Energy Technology Data Exchange (ETDEWEB)

    Loesche, W.M.; Mazurov, A.V.; Heptinstall, S.; Groenewegen, W.A.; Repin, V.S.; Till, U.


    The interaction of platelets with surfaces coated with collagens of type III (C III) or IV (C IV) has been studied by measuring the deposition of /sup 51/Cr-labeled platelets and by scanning electron microscopy (SEM). Experiments were performed using platelet-rich plasma (PRP) and suspensions of gel-filtered platelets (GFP). Platelets were deposited on C III mainly as surface-bound aggregates. In contrast they were deposited on C IV mainly as spread forms of individual cells. Formation of aggregates on C III was more extensive for PRP than for GFP; in contrast platelet spreading on C IV was more extensive for GFP than for PRP. The effects of an extract of the plant feverfew on platelet-collagen interactions were determined. Feverfew extract inhibited the deposition of /sup 51/Cr-labeled platelets on both C III and C IV in a dose-dependent way. Similar concentrations of extract were needed to inhibit the formation of surface-bound aggregates and to inhibit platelet spreading in both PRP and GFP.

  17. Homocysteine and its thiolactone may promote apoptotic events in blood platelets in vitro. (United States)

    Olas, Beata; Malinowska, Joanna; Rywaniak, Joanna


    The actions of homocysteine and its major metabolite, cyclic thioester, homocysteine thiolactone on endothelial cells, blood platelets, plasmatic fibrinogen and plasminogen--the important major components of haemostasis, regulating the flowing properties of blood--are complex and sometimes controversial. Homocysteine (Hcys) can promote apoptosis in endothelial cells, but the role of Hcys and its thiolactone in the apoptotic process in blood platelets is unknown. In order to study the appearance of apoptosis in platelets after treatment with the reduced form of Hcys or its thiolactone different markers were chosen: annexin V binding (phosphatidylserine exposure), platelet microparticle formation, mitochondrial membrane depolarization and αIIbβ3 expression in vitro. Apoptotic events and platelet activation were measured by a flow cytometer. In gel-filtered platelets treated with different concentrations of the reduced form of Hcys (25, 50 and 100 µM, 10 min) a significant increase of phosphatidylserine exposure (about 37% at the highest concentration, p < 0.001) and platelet microparticle formation were observed. Homocysteine caused also a dose-dependent depolarization of mitochondrial potential. The same apoptotic markers appeared in HTL-treated platelets (0.2 and 1 µM). Moreover, resveratrol (25 µM), a well known antioxidant, distinctly reduced the level of apoptotic markers. The obtained results indicate that Hcys and its thiolactone may promote in vitro apoptotic events in human gel-filtered platelets.

  18. Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase. (United States)

    Blair, Price; Rex, Sybille; Vitseva, Olga; Beaulieu, Lea; Tanriverdi, Kahraman; Chakrabarti, Subrata; Hayashi, Chie; Genco, Caroline A; Iafrati, Mark; Freedman, Jane E


    Cells of the innate immune system use Toll-like receptors (TLRs) to initiate the proinflammatory response to microbial infection. Recent studies have shown acute infections are associated with a transient increase in the risk of vascular thrombotic events. Although platelets play a central role in acute thrombosis and accumulating evidence demonstrates their role in inflammation and innate immunity, investigations into the expression and functionality of platelet TLRs have been limited. In the present study, we demonstrate that human platelets express TLR2, TLR1, and TLR6. Incubation of isolated platelets with Pam(3)CSK4, a synthetic TLR2/TLR1 agonist, directly induced platelet aggregation and adhesion to collagen. These functional responses were inhibited in TLR2-deficient mice and, in human platelets, by pretreatment with TLR2-blocking antibody. Stimulation of platelet TLR2 also increased P-selectin surface expression, activation of integrin alpha(IIb)beta(3), generation of reactive oxygen species, and, in human whole blood, formation of platelet-neutrophil heterotypic aggregates. TLR2 stimulation also activated the phosphoinositide 3-kinase (PI3-K)/Akt signaling pathway in platelets, and inhibition of PI3-K significantly reduced Pam(3)CSK4-induced platelet responses. In vivo challenge with live Porphyromonas gingivalis, a Gram-negative pathogenic bacterium that uses TLR2 for innate immune signaling, also induced significant formation of platelet-neutrophil aggregates in wild-type but not TLR2-deficient mice. Together, these data provide the first demonstration that human platelets express functional TLR2 capable of recognizing bacterial components and activating the platelet thrombotic and/or inflammatory pathways. This work substantiates the role of platelets in the immune and inflammatory response and suggests a mechanism by which bacteria could directly activate platelets.

  19. Engineering activities on the ITER representative diagnostic equatorial port plug

    Energy Technology Data Exchange (ETDEWEB)

    Meunier, L. [Association Euratom CEA, CEA/DSM/IRFM (France)], E-mail:; Doceul, L.; Salasca, S.; Martins, J.-P.; Jullien, F.; Dechelle, Christian; Bidaud, Pierre; Pilard, Vincent; Terra, Alexis; Ogea, Mathieu [Association Euratom CEA, CEA/DSM/IRFM (France); Ciattaglia, Emanuela [EFDA CSU, Garching (Germany); Walker, Christopher [ITER International Organisation (France)


    Most of ITER diagnostic systems are integrated in port plugs, which are water cooled stainless steel structures inserted into the vacuum vessel ports. The port plug must provide basic functions such as neutron and gamma shielding, supporting the first wall armour (BSM), closing the vacuum vessel ports, while supporting the diagnostic equipments. ITER diagnostic port plug must resist a severe environment like high temperature due to neutron interaction with the structures and high electromechanical loading during disruptions events. CEA has contributed to the design and integration tasks in the frame of the representative equatorial port plug EQ no. 01, in particular on the engineering, structural and thermal finite element analysis. These detailed analyses have highlighted some design issues which were worked out through different solutions. This paper contains a description of the engineering activities performed such as: -The static mechanical calculations of the top plate closure system under disruption load. -The static mechanical calculations of the BSM attachment to the port plug. These two first studies led to design changes proposals which significantly improved the behaviour of the structures but also showed that the safety margin with respect to design limits is quite low. -The design of a Diagnostic Shield Module (DSM) integrated inside the port plug and a proposition of attachment scheme, with respect to disruption loads. The manufacturing of the DSM has been taken into account, as well as diagnostic integration inside the structure and maintenance aspects. -The thermal assessment of the port plug under neutronic load during normal operation, with the optimization of the cooling system. The maximum temperature calculated in normal operation has been reduced from 900 deg. C to less than 400 deg. C in the front plate; and the cooling arrangement at the back of the port plug has been simplified without important temperature increase.

  20. Extract of a spice--omum (Trachyspermum ammi)-shows antiaggregatory effects and alters arachidonic acid metabolism in human platelets. (United States)

    Srivastava, K C


    An ethereal extract of omum (Trachyspermum ammi; Hindustani: ajwan)--a frequently consumed spice--was found to inhibit platelet aggregation induced by arachidonic acid (AA), epinephrine and collagen; in this respect it was most effective against AA-induced aggregation. Inhibition of aggregation by omum could be explained by its effect on platelet thromboxane production as suggested by the following experimental observation. (i) Omum reduced TxB2 formation in intact platelet preparations from added arachidonate, and (ii) it reduced the formation of TxB2 from AA-labelled platelets after stimulation with Ca2+-ionophore A23187 by a direct action on cyclooxygenase as it did not affect the release of AA from labelled platelets. An increased formation of lipoxygenase-derived products from exogenous AA in omum-treated platelets was apparently due to redirection of AA from cyclooxygenase to the lipoxygenase pathway.

  1. Platelet activation through a Bi-leaflet mechanical heart valve (United States)

    Hedayat, Mohammadali; Borazjani, Iman


    Platelet activation is one of the major drawbacks of the Mechanical Heart Valves (MHVs) which can increase the risk of thrombus formation in patients. The platelet activation in MHVs can be due to the abnormal shear stress during the systole, the backward leakage flow during the diastole, and the flow through the hinge region. We investigate the contribution of each of the above mechanism to the activation of platelets in MHVs by performing simulations of the flow through the MHV and in the hinge region. The large scale heart valve simulations are performed in a straight aorta using a sharp interface curvilinear immersed boundary method along with a strong-coupling algorithm under physiological flow conditions. In addition, in order to perform the simulation of hinge region the flow field boundary conditions are obtained from the largescale simulations during a whole cardiac cycle. In order to investigate the role of hinge flow on platelet activation in MHVs, a 23mm St. Jude Medical Regent valve hinge with three different gap sizes is tested along with different platelet activation models to ensure the consistency of our results with different activation models. We compare the platelet activation of the hinge region against the bulk of the flow during one cardiac cycle. This work is supported by the American Heart Association Grant 13SDG17220022, and the computational resources were partly provided by Center for Computational Research (CCR) at University at Buffalo.

  2. Identification of the platelet ADP receptor targeted by antithrombotic drugs. (United States)

    Hollopeter, G; Jantzen, H M; Vincent, D; Li, G; England, L; Ramakrishnan, V; Yang, R B; Nurden, P; Nurden, A; Julius, D; Conley, P B


    Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.

  3. Platelet activation and platelet-leukocyte interaction in dogs naturally infected with Babesia rossi

    DEFF Research Database (Denmark)

    Goddard, Amelia; Leisewitz, Andrew L; Kristensen, Annemarie Thuri;


    EDTA as anticoagulant. Activated platelets and PLA formation were detected by measuring surface expression of P-selectin (CD62P) on platelets, monocytes and neutrophils. Of the Babesia-infected dogs, 29 survived and seven died. The percentage of CD62P-positive monocytes was significantly higher (P = 0.......036) in the Babesia-infected dogs (54%) than in healthy control dogs (35.3%). However, there were no significant differences between the Babesia-infected and control groups for CD62P-positive platelets (4.9% and 1.2%, respectively) and CD62P-positive neutrophils (28.3% and 17.9%, respectively). The percentage of CD62...... groups for the percentage of CD62P-positive platelets (survivors 4.8%; non-survivors 5.3%; controls 1.2%) or CD62P-positive neutrophils (survivors 31.6%; non-survivors 5.6%; controls 17.9%). In conclusion, Babesia-infected dogs, specifically dogs that survived, had a significantly increased percentage...

  4. IgG+ platelets in the marmoset: their induction, maintenance, and survival

    Energy Technology Data Exchange (ETDEWEB)

    Gengozian, N.; McLaughlin, C.L.


    Immunization of marmosets with platelets from another species of marmoset leads to antibody formation to the donor platelets, deposition of IgG on the host's platelets, and thrombocytopenia. This disease closely resembles posttransfusion purpura of man, which may develop after one or two transfusions of whole blood. The mode of immunization in the marmoset was found to be important: intravenous (i.v.) inoculations were without effect, while intramuscular (i.m.) immunizations led to the disease. Intramuscular inoculations were characterized by formation of 7S antibodies, as measured by indirect immunofluorescent (IF) and complement-dependent platelet cytotoxicity (PC) tests; in contrast, i.v. immunizations, while leading to 7S antibodies by the IF test, yielded only 19S antibodies reactive in the PC assay. The titers were also consistently higher with i.m. immunizations. Antibody was not limited to the donor platelets, but auto- or host-type reactivity was also present; this antibody was in very low titer and could be found only when the animal was thrombocytopenic. A primary finding was the ability to maintain increased deposition of IgG on the host's platelets in the absence of thrombocytopenia by biweekly or monthly inoculations of the donor platelet antigen. The amount of IgG found on platelets of normal and immunized marmosets was comparable to that reported for normal humans and patients with cinical immune thrombocytopenia. Finally, platelet survival studies in animals with IgG+ platelets and normal platelet counts indicated a rapid turnover, suggesting operation of a compensatory mechanism to maintain platelet levels.

  5. Circulating primers enhance platelet function and induce resistance to antiplatelet therapy (United States)

    Blair, T A; Moore, S F; Hers, I


    Background Aspirin and P2Y12 antagonists are antiplatelet compounds that are used clinically in patients with thrombosis. However, some patients are ‘resistant’ to antiplatelet therapy, which increases their risk of developing acute coronary syndromes. These patients often present with an underlying condition that is associated with altered levels of circulating platelet primers and platelet hyperactivity. Platelet primers cannot stimulate platelet activation, but, in combination with physiologic stimuli, significantly enhance platelet function. Objectives To explore the role of platelet primers in resistance to antiplatelet therapy, and to evaluate whether phosphoinositide 3-kinase (PI3K) contributes to this process. Methods and Results We used platelet aggregation, thromboxane A2 production and ex vivo thrombus formation as functional readouts of platelet activity. Platelets were treated with the potent P2Y12 inhibitor AR-C66096, aspirin, or a combination of both, in the presence or absence of the platelet primers insulin-like growth factor-1 (IGF-1) and thrombopoietin (TPO), or the Gz-coupled receptor ligand epinephrine. We found that platelet primers largely overcame the inhibitory effects of antiplatelet compounds on platelet functional responses. IGF-1-mediated and TPO-mediated, but not epinephrine-mediated, enhancements in the presence of antiplatelet drugs were blocked by the PI3K inhibitors wortmannin and LY294002. Conclusions These results demonstrate that platelet primers can contribute to antiplatelet resistance. Furthermore, our data demonstrate that there are PI3K-dependent and PI3K-independent mechanisms driving primer-mediated resistance to antiplatelet therapy. PMID:26039631


    Barinov, E F


    Objective of the research was to determine involvement of platelets and the role of adrenaline in chronic inflammation maintaining and the initiation of acute inflammatory response in elderly patients with chronic obstructive pyelonephritis against this background. The study includes 60 patients with chronic obstructive pyelonephritis (COPN), which are distributed into two groups: basic - 22 elderly patients (age 73±1,5 years) and the comparison group - 38 middle-aged patients (52,5±2,4 years). The study excluded patients who took antiplatelet drugs and non-selective blockers of α adrenergic receptors at least 1 week before the study. Analysis of platelets adrenoreactivity in vitro was carried out at the time of hospitalization before the start of conservative therapy. Platelet-rich plasma was isolated from peripheral blood by centrifuging. ADP and epinephrine were used in the effective (EC50) and sub-threshold (EC10) concentrations to stimulate platelets. The formation of platelet-leukocyte aggregates was reproduced in vitro upon incubation of stimulated platelets (at a concentration of adrenaline EC50) and intact leukocytes isolated from patient peripheral blood. The study of platelet reactivity revealed that in elderly patients acute inflammatory response realization (relapse of COPN) is against optimal functioning of platelets α2 adrenergic receptors. Significant increase in the number of platelet-leukocyte aggregates is possible. Remission of COPN (the presence of chronic inflammation) in the examined patients of various ages was associated with platelet hypoadrenoreactivity. Increased platelet adrenoreactivity during transition from remission to relapse of COPN in the elderly patients is possible if adequate synthesis of ADP in platelets and its secretion from dense granules are preserved. The observed interaction of adrenaline and ADP with stimulated platelet hyporesponsiveness probably ensures adaptive response aimed at acute inflammatory response in

  7. High quality new type spark plug pressure sensor; Koseino plug gata shiatsu sensor ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Urakawa, H.; Yanagihara, S.; Kawa, T. [Tsukasa Sokken Co. Ltd., Tokyo (Japan); Enomoto, Y. [Musashi Institute of Technology, Tokyo (Japan); Sato, T. [Dai Ichi Institute of Technology, Kagoshima (Japan); Gotthard, E.


    Investigations were made on a spark plug type pressure sensor using GaPO4 piezoelectric material developed recently by AVL Corporation. This sensor has the ignition electrode installed decentered to assure the installing position for the pressure sensor, where the small pressure sensor with a diameter of 4.4 mm, model GU12P is installed on the side. Experiments were performed on this sensor, a water cooled sensor for comparison, and a cooling-free type sensor for reference. The engine was operated at an outlet cooling water temperature maintained constant at 80 degC, and experimented in a normal combustion condition with full load at 2000 rpm and 4000 rpm, in a knocking condition with full load at 2000 rpm, and in a transient condition from full load at 4000 rpm to no load at 1300 rpm. As a result, it was made clear that the spark plug type pressure sensor showed an output of the same level as that with the water cooled sensor in the normal combustion pressure. Load change drift under the transient condition was found as good as 2.5% FS at maximum. No effect of columnar vibration was discovered, and a knocking waveform of 14 kHz was observed. 6 refs., 12 figs., 1 tab.

  8. The GPIIb/IIIa antagonist eptifibatide markedly potentiates platelet-leukocyte interaction and tissue factor expression following platelet activation in whole blood in vitro. (United States)

    Scholz, Thomas; Zhao, Lian; Temmler, Uta; Bath, Philip; Heptinstall, Stan; Lösche, Wolfgang


    Tissue factor (TF) is the most important initiator of intravascular coagulation. Activated platelets are able to adhere to leukocytes and this heterotypic cell-cell interaction results in a CD62P-dependent TF expression on monocytes. GPIIb/IIIa antagonists are inhibitors of the common pathway of platelet aggregation and they are widely used in patients with acute coronary syndromes undergoing coronary interventions. As GPIIb/IIIa antagonists do not prevent platelet activation we investigated the effect a GPIIb/IIIa antagonist, eptifibatide, on the formation of platelet-leukocyte conjugates and leukocyte TF expression. Flow cytometry was used to detect conjugates and TF. When platelets in citrated human blood were stimulated for 30 min with collagen there was a increase in the number of both neutrophils and monocytes with the platelet-specific antigen CD42a, indicating the formation of platelet-neutrophil (P/N) and platelet-monocyte (P/M) conjugates. P/M formation was associated with about a 2.5-fold increase in TF expression on monocytes, whereas P/N formation changed TF expression neutrophils only by about 10%. Eptifibatide enhanced dose-dependently (0.0625-1.5 microg/ml) both collagen-induced P/M formation and monocyte TF expression. Maximum enhancement by about 60 and 120%, respectively, was observed at 0.5 microg/ml eptifibatide. In contrast, eptifibatide had only a minor effect on P/N formation and no effect on neutrophil TF expression. The augmented P/M formation and monocyte TF expression in the presence of a GPIIb/IIIa antagonist may be relevant to the poor antithrombotic efficiency of oral GPIIb/IIIa antagonists as shown in recent large clinical trials.

  9. [Effect of dauricine on rat and human platelet aggregation and metabolism of arachidonic acid in washed rat platelets]. (United States)

    Tong, L; Yue, T L


    Dauricine (Dau), an isoquinoline alkaloid extracted from the roots of Menispermum dauricum D. C. and used as an antiarrhythmic agent in China recently, was shown to inhibit rat platelet aggregation induced by arachidonic acid (AA) and ADP, as well as human platelet aggregation induced by AA, ADP and adrenaline (Adr) in vitro in a dose-dependent manner. The concentration of Dau required for 50% inhibition (IC50) of rat platelet aggregation induced by AA and ADP was 26 and 37 mumol/L, respectively. For human platelet aggregation induced by AA, ADP and Adr the IC50 of Dau was found to be 39, 55 and 43 mumol/L, respectively. Dau inhibited the cyclooxygenase pathway metabolites of AA (TXB2 and HHT) in washed intact rat platelets. The production of TXB2 and HHT was reduced by 26% and 19%, respectively, when the Dau concentration was 50 mumol/L and by 46 and 45%, respectively, when the concentration of Dau was 100 mumol/L. The formation of 12-HETE was also inhibited at 100 mumol/L of Dau. The inhibitory effect of Dau on AA metabolism may be one of the mechanisms related to its inhibition of platelet aggregation.

  10. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice. (United States)

    Deppermann, Carsten; Cherpokova, Deya; Nurden, Paquita; Schulz, Jan-Niklas; Thielmann, Ina; Kraft, Peter; Vögtle, Timo; Kleinschnitz, Christoph; Dütting, Sebastian; Krohne, Georg; Eming, Sabine A; Nurden, Alan T; Eckes, Beate; Stoll, Guido; Stegner, David; Nieswandt, Bernhard


    Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, α-granules, release proteins that participate in thrombus formation and hemostasis. Proteins stored in α-granules are also thought to play a role in inflammation and wound healing, but their functional significance in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet syndrome (GPS), a rare bleeding disorder characterized by macrothrombocytopenia, with platelets lacking α-granules. Here we show that Nbeal2-knockout mice display the characteristics of human GPS, with defective α-granule biogenesis in MKs and their absence from platelets. Nbeal2 deficiency did not affect MK differentiation and proplatelet formation in vitro or platelet life span in vivo. Nbeal2-deficient platelets displayed impaired adhesion, aggregation, and coagulant activity ex vivo that translated into defective arterial thrombus formation and protection from thrombo-inflammatory brain infarction following focal cerebral ischemia. In a model of excisional skin wound repair, Nbeal2-deficient mice exhibited impaired development of functional granulation tissue due to severely reduced differentiation of myofibroblasts in the absence of α-granule secretion. This study demonstrates that platelet α-granule constituents are critically required not only for hemostasis but also thrombosis, acute thrombo-inflammatory disease states, and tissue reconstitution after injury.

  11. Analyzing the platelet proteome. (United States)

    García, Angel; Zitzmann, Nicole; Watson, Steve P


    During the last 10 years, mass spectrometry (MS) has become a key tool for protein analysis and has underpinned the emerging field of proteomics. Using high-throughput tandem MS/MS following protein separation, it is potentially possible to analyze hundreds to thousands of proteins in a sample at a time. This technology can be used to analyze the protein content (i.e., the proteome) of any cell or tissue and complements the powerful field of genomics. The technology is particularly suitable for platelets because of the absence of a nucleus. Cellular proteins can be separated by either gel-based methods such as two-dimensional gel electrophoresis or one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by liquid chromatography (LC) -MS/MS or by multidimensional LC-MS/MS. Prefractionation techniques, such as subcellular fractionations or immunoprecipitations, can be used to improve the analysis. Each method has particular advantages and disadvantages. Proteomics can be used to compare the proteome of basal and diseased platelets, helping to reveal information on the molecular basis of the disease.

  12. Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation

    Directory of Open Access Journals (Sweden)

    Yi Chang


    Full Text Available Pomegranates are widely consumed either as fresh fruit or in beverage form as juice and wine. Ellagic acid possesses potent antioxidative properties; it is known to be an effective phytotherapeutic agent with antimutagenic and anticarcinogenic qualities. Ellagic acid (20 to 80 μM exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619. Treatment with ellagic acid (50 and 80 μM significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca2+]i mobilization, and the phosphorylation of phospholipase C (PLCγ2, protein kinase C (PKC, mitogen-activated protein kinases (MAPKs, and Akt, as well as hydroxyl radical (OH● formation. In addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC activation and platelet aggregation stimulated by PDBu. This study is the first to show that, in addition to being considered a possible agent for preventing tumor growth, ellagic acid possesses potent antiplatelet properties. It appears to initially inhibit the PLCγ2-PKC cascade and/or hydroxyl radical formation, followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting platelet aggregation.

  13. Platelet granule exocytosis: A comparison with chromaffin cells

    Directory of Open Access Journals (Sweden)

    Jennifer eFitch-Tewfik


    Full Text Available The rapid secretion of bioactive amines from chromaffin cells constitutes an important component of the fight or flight response of mammals to stress. Platelets respond to stresses within the vasculature by rapidly secreting cargo at sites of injury, inflammation, or infection. Although chromaffin cells derive from the neural crest and platelets from bone marrow megakaryocytes, both have evolved a heterogeneous assemblage of granule types and a mechanism for efficient release. This article will provide an overview of granule formation and exocytosis in platelets with an emphasis on areas in which the study of chromaffin cells has influenced that of platelets and on similarities between the two secretory systems. Commonalities include the use of transporters to concentrate bioactive amines and other cargos into granules, the role of cytoskeletal remodeling in granule exocytosis, and the use of granules to provide membrane for cytoplasmic projections. The SNAREs and SNARE accessory proteins used by each cell type will also be considered. Finally, we will discuss the newly appreciated role of dynamin family proteins in regulated fusion pore formation. This evaluation of the comparative cell biology of regulated exocytosis in platelets and chromaffin cells demonstrates a convergence of mechanisms between two disparate cell types both tasked with responding rapidly to physiological stimuli.

  14. Effect of platelet-derived growth factor on rabbit corneal wound healing. (United States)

    Stern, M E; Waltz, K M; Beurerman, R W; Ghosn, C R; Mantras, C E; Nicolson, M; Assouline, M; Stern, K L; Wheeler, L A


    Human recombinant platelet-derived growth factor was evaluated with the use of wound healing models in New Zealand albino rabbits. The efficacy of the platelet-derived growth factor dimers, AA, AB, and BB, was determined in corneal reepithelialization and anterior keratectomy models which examined the healing response in the presence or absence of the basement membrane. All dimers increased the rate of wound healing in both models at 100 microg/ml when compared with control; however, the platelet-derived growth factor-BB isoform showed the most dramatic increase in both studies. The strength of the healing stroma after incision was evaluated by means of a tensile strength model. Histologic evaluation of the stromal wound area after 9 days of healing showed a marked increase in the number of keratocytes within the wound bed of the corneas treated with platelet-derived growth factor-BB when compared with control corneas. In addition, at 9 days, the epithelial plug was still present in the control corneas but had been extruded to the surface by the granulation tissue in the platelet-derived growth factor-BB-treated corneas. These results are indicative of a more advanced stage of healing in treated versus control wounds at 9 days after the operation. A 30% increase in corneal tensile strength versus control was noted after 21 days of healing. Finally, in an in vitro gel contraction assay, platelet-derived growth factor exhibited a dose-dependent effect on the contraction of fibroblasts for doses ranging from 0.01 to 10 ng/ml. These results indicate that platelet-derived growth factor is active in the corneal wound healing process.

  15. Methodology for physical modeling of melter electrode power plug

    Energy Technology Data Exchange (ETDEWEB)

    Heath, W.O.


    A method is presented for building and testing a one-third scale model of an electrode power plug used to supply up to 3000 amperes to a liquid fed ceramic melter. The method describes how a one-third scale model can be used to verify the ampacity of the power plug, the effectiveness of the power plug cooling system and the effect of the high amperage current on eddy current heating of rebar in the cell wall. Scale-up of the test data, including cooling air flow rate and pressure drop, temperature profiles, melter water jacket heat duty and electrical resistance is covered. The materials required to build the scale model are specified as well as scale surface finish and dimensions. The method for designing and testing a model power plug involves developing a way to recreate the thermal conditions including heat sources, sinks and boundary temperatures on a scale basis. The major heat sources are the molten glass in contact with the electrode, joule heat generation within the power plug, and eddy current heating of the wall rebar. The melting cavity heat source is modelled using a plate heater to provide radiant heat transfer to a geometrically similar, one-third scale electrode housed in a scale model of a melting cavity having a thermally and geometrically similar wall and floor. The joule heat generation within the power plug is simulated by passing electricity through the model power plug with geometrically similar rebar positioned to simulate the eddy heating phenomenon. The proposed model also features two forced air cooling circuits similar to those on the full design. The interaction of convective, natural and radiant heat transfer in the wall cooling circuit are considered. The cell environment and a melter water jacket, along with the air cooling circuits, constitute the heat sinks and are also simulated.

  16. Reduced-dimension model of liquid plug propagation in tubes (United States)

    Fujioka, Hideki; Halpern, David; Ryans, Jason; Gaver, Donald P.


    We investigate the flow resistance caused by the propagation of a liquid plug in a liquid-lined tube and propose a simple semiempirical formula for the flow resistance as a function of the plug length, the capillary number, and the precursor film thickness. These formulas are based on computational investigations of three key contributors to the plug resistance: the front meniscus, the plug core, and the rear meniscus. We show that the nondimensional flow resistance in the front meniscus varies as a function of the capillary number and the precursor film thickness. For a fixed capillary number, the flow resistance increases with decreasing precursor film thickness. The flow in the core region is modeled as Poiseuille flow and the flow resistance is a linear function of the plug length. For the rear meniscus, the flow resistance increases monotonically with decreasing capillary number. We investigate the maximum mechanical stress behavior at the wall, such as the wall pressure gradient, the wall shear stress, and the wall shear stress gradient, and propose empirical formulas for the maximum stresses in each region. These wall mechanical stresses vary as a function of the capillary number: For semi-infinite fingers of air propagating through pulmonary airways, the epithelial cell damage correlates with the pressure gradient. However, for shorter plugs the front meniscus may provide substantial mechanical stresses that could modulate this behavior and provide a major cause of cell injury when liquid plugs propagate in pulmonary airways. Finally, we propose that the reduced-dimension models developed herein may be of importance for the creation of large-scale models of interfacial flows in pulmonary networks, where full computational fluid dynamics calculations are untenable.

  17. Changes in the level of cytosolic calcium, nitric oxide and nitric oxide synthase activity during platelet aggregation: an in vitro study in platelets from normal subjects and those with cirrhosis

    Indian Academy of Sciences (India)

    Sam Annie-JeyachristYn; Arumugam Geetha; Rajagopal Surendran


    Variceal bleeding due to abnormal platelet function is a well-known complication of cirrhosis. Nitric oxide-related stress has been implicated in the pathogenesis of liver cirrhosis. In the present investigation, we evaluated the level of platelet aggregation and concomitant changes in the level of platelet cytosolic calcium (Ca2+), nitric oxide (NO) and NO synthase (NOS) activity in liver cirrhosis. The aim of the present study was to investigate whether the production of NO by NOS and level of cytosolic Ca2+ influence the aggregation of platelets in patients with cirrhosis of the liver. Agonist-induced aggregation and the simultaneous changes in the level of cytosolic Ca2+, NO and NOS were monitored in platelets of patients with cirrhosis. Platelet aggregation was also measured in the presence of the eNOS inhibitor, diphenylene iodinium chloride (DIC). The level of agonist-induced platelet aggregation was significantly low in the platelets of patients with cirrhosis compared with that in platelets from normal subjects. During the course of platelet aggregation, concomitant elevation in the level of cytosolic Ca2+ was observed in normal samples, whereas the elevation was not significant in platelets of patients with cirrhosis. A parallel increase was observed in the levels of NO and NOS activity. In the presence of the eNOS inhibitor, platelet aggregation was enhanced and accompanied by an elevated calcium level. The inhibition of platelet aggregation in liver cirrhosis might be partly due to greater NO formation by eNOS. Defective Ca2+ release from the internal stores to the cytosol may account for inhibition of aggregation of platelets in cirrhosis. The NO-related defective aggregation of platelets in patients with cirrhosis found in our study is of clinical importance, and the underlying mechanism of such changes suggests a possible therapeutic strategy with cell-specific NO blockers.

  18. Prolactin does not affect human platelet aggregation or secretion

    NARCIS (Netherlands)

    Reuwer, A.Q.; Nieuwland, R.; Fernandez, I.; Goffin, V.; van Tiel, C.M.; Schaap, M.C.L.; Berckmans, R.J.; Kastelein, J.J.P.; Twickler, M.T.B.


    Platelets play an important role in the development of plaque formation and in the events after rupture of the atherosclerotic plaque, leading to atherothrombosis. Multiple hormones, either in excess or when deficient, are involved in the development of atherothrombotic disease, but, to which extent

  19. Evaluation of triple anti-platelet therapy by modified thrombelastography in patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    REN Yi-hong; JIN Jing; XIN You-hong; LI Rong-bin; LI Hai-yan; LIN Lin; LIU Chun-xue; YANG Ting-shu; WANG Yu; GAI Lu-yue; LIU Hong-bin; CHEN Lian; WANG Hong-ye; WANG Chun-ya; XU Xiu-li


    @@ Most cases of acute coronary syndrome (ACS) involve coronary atherosclerosis and plaque rupture,as well as subsequent thrombosis. The initial thrombotic events leading to red thrombus formation are platelet adherence and aggregation.

  20. Estimation of Heights of Soil Plug Inside Bucket Foundations During Suction Penetration by Deformable Discrete Element Modeling

    Institute of Scientific and Technical Information of China (English)


    The soil plug phenomenon involving the rising of the surface soil inside the bucket chamber under the suction pressure and seepage forces was simulated and calculated by deformable discrete element method (DDEM) models. The seepage forces, the effective gravity of soil, the friction on the chamber wall and the suction inside the chamber are considered as the main external forces of DDEM specimen. Three typical types of soil (silty clay, silt and sand) in the Bohai Sea are set as the main environmental conditions in the formation process of soil plug. It is found that the heights of soil plug simulated by DDEM models are 161.85 mm in silty clay, 125.22 mm in silt and 167.56 mm in sand, which are close to model test results and higher than those estimated by discrete element method (DEM). DDEM is an effective method to estimate and predict the heights of soil plug before suction penetration of bucket foundations on site.

  1. VAMP-7 links granule exocytosis to actin reorganization during platelet activation. (United States)

    Koseoglu, Secil; Peters, Christian G; Fitch-Tewfik, Jennifer L; Aisiku, Omozuanvbo; Danglot, Lydia; Galli, Thierry; Flaumenhaft, Robert


    Platelet activation results in profound morphologic changes accompanied by release of granule contents. Recent evidence indicates that fusion of granules with the plasma membrane during activation provides auxiliary membrane to cover growing actin structures. Yet little is known about how membrane fusion is coupled with actin reorganization. Vesicle-associated membrane protein (VAMP)-7 is found on platelet vesicles and possesses an N-terminal longin domain capable of linking exocytosis to cytoskeletal remodeling. We have evaluated platelets from VAMP-7(-/-) mice to determine whether this VAMP isoform contributes to granule release and platelet spreading. VAMP-7(-/-) platelets demonstrated a partial defect in dense granule exocytosis and impaired aggregation. α Granule exocytosis from VAMP-7(-/-) platelets was diminished both in vitro and in vivo during thrombus formation. Consistent with a role of VAMP-7 in cytoskeletal remodeling, spreading on matrices was decreased in VAMP-7(-/-) platelets compared to wild-type controls. Immunoprecipitation of VAMP-7 revealed an association with VPS9-domain ankyrin repeat protein (VARP), an adaptor protein that interacts with both membrane-bound and cytoskeleton proteins and with Arp2/3. VAMP-7, VARP, and Arp2/3 localized to the platelet periphery during spreading. These studies demonstrate that VAMP-7 participates in both platelet granule secretion and spreading and suggest a mechanism whereby VAMP-7 links granule exocytosis with actin reorganization.

  2. Platelet Hyperactivity in TNFSF14/LIGHT Knockout Mouse Model of Impaired Healing. (United States)

    Dhall, Sandeep; Karim, Zubair A; Khasawneh, Fadi T; Martins-Green, Manuela


    Objective: Impaired and chronic wounds occur due to defects in one or more of the overlapping stages of healing. However, problems related to the vascular system are critical for nonhealing, and chronic wounds in humans often show the presence of fibrin cuffs/clots. We hypothesized that these clots are due to alterations in platelet function; hence, we have investigated whether alterations in platelet function are present during impaired healing. Approach: Platelets were subjected to different agonists to determine the rate of aggregation and evaluate the molecules involved in adhesion and aggregation that could lead to faster thrombosis and potentially contribute to impaired wound healing. Results: We show that wounding of TNFSF14/LIGHT(-/-) mice, which have impaired healing, leads to an enhanced response in platelet aggregation and a faster time to blood vessel occlusion (thrombosis). In addition, after wounding, platelets from these mice have increased levels of P-selectin, integrin αIIbβ3, and phosphatidylserine, molecules that contribute to platelet adhesion. They also have more extensive open canalicular system than platelets of control mice, suggesting increased surface area for interactions upon activation. Innovation: These results show a novel function for TNFSF14/LIGHT during wound healing. Conclusion: The absence of TNFSF14/LIGHT from the cell surface of platelets causes rapid platelet aggregation and thrombus formation that may contribute to impaired healing by reducing the ability of the blood vessels to transport nutrients and oxygen and other molecules needed for proper healing.

  3. Arachidonic acid metabolism in the platelets and neutrophils of diabetic rabbit and human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Greco, N.J.


    An alteration of arachidonic acid metabolism to prostaglandins and leukotrienes from platelets and polymorphonuclear leukocytes respectively is evident in subjects with diabetes mellitus. There is evidence of altered platelet/vascular wall interactions in diabetes mellitus and evidence that polymorphonuclear leukocytes influence the vascular walls. Theories on the pathogenesis of atherosclerosis include both blood cells. Platelet hypersensitivity is evident in those platelets from the alloxan-induced diabetic rabbit either suspended in plasma or buffer. Arachidonic acid- and collagen-induced platelet aggregation, release of /sup 14/serotonin, and T x B/sub 2/ and 12-HETE production is enhanced when responses of diabetic platelets are compared to control platelets. Control rabbit neutrophils produce more LTB/sub 4/, LTB/sub 4/ isomers and 5-HETE than diabetic rabbits neutrophils. Decreased synthesis from diabetic rabbit neutrophils is not explained by increased catabolism of LTB/sub 4/, reesterification of 5-HETE, or increased eicosanoid formation. These experiments demonstrate both platelet and neutrophil dysfunction in diabetic subjects. Because of the involvement of these cells in regulating circulatory homeostatis, abnormal behavior could aggravate the atherosclerotic process. Platelet and neutrophil dysfunctions are noted before macroscopic vascular lesions are apparent suggesting an important role in the pathogenesis of atherosclerosis.

  4. Effects of Nd:YAG laser-heated metal cap on human platelets in vitro (United States)

    Liu, Xia; Guo, You-chi


    Human platelet-rich plasma (PRP) was irradiated in vitro with a fiberoptic Nd:YAG laser-heated metal cap to study its effects on platelets. The energy of the laser was 5 and 10 watts with an irradiation time of 0, 3, 6, and 9 seconds and 14 watts with an irradiation time of 0, 3, 4, and 5 seconds, respectively. The irradiated PRPs were analyzed for platelet count, aggregation reaction, thromboxane (TX)B2 measurement and electron microscopy. Various degrees of decrease in platelet count were observed in all groups. Except the 5Wx3S group, the other groups showed an increase in the maximum aggregation rate of platelets, which corresponded to the enhancement of TXB2 formation. It was also demonstrated by a transmission electron microscopy in 10Wx3S, 10Wx6S, 10Wx9S, 14Wx3S, 14Wx4S, and 14Wx5S energy groups that alpha- and dense-particles in irradiated platelets became sparse in number or even disappeared, less electron density, irregularity in size and shape, and a tendency for these particles to cluster around platelet membranes and open canalicular systems, which dilated apparently. Furthermore, scanning electron microscopy depicted the appearance of short and thick pseudopods on the surfaces of some irradiated platelets and an increase in the axis rate in most of the irradiated platelets.

  5. Platelets in inflammation and infection. (United States)

    Jenne, Craig N; Kubes, Paul


    Although platelets are traditionally recognized for their central role in hemostasis, many lines of research clearly demonstrate these rather ubiquitous blood components are potent immune modulators and effectors. Platelets have been shown to directly recognize, sequester and kill pathogens, to activated and recruit leukocytes to sites of infection and inflammation, and to modulate leukocyte behavior, enhancing their ability to phagocytose and kill pathogens and inducing unique effector functions, such as the production of Neutrophil Extracellular Traps (NETs). This multifaceted response to infection and inflammation is due, in part, to the huge array of soluble mediators and cell surface molecules expressed by platelets. From their earliest origins as primordial hemocytes in invertebrates to their current form as megakaryocyte-derived cytoplasts, platelets have evolved to be one of the key regulators of host intravascular immunity and inflammation. In this review, we present the diverse roles platelets play in immunity and inflammation associated with autoimmune diseases and infection. Additionally, we highlight recent advances in our understanding of platelet behavior made possible through the use of advanced imaging techniques that allow us to visualize platelets and their interactions, in real-time, within the intact blood vessels of a living host.

  6. [Murine models of platelet diseases]. (United States)

    Lanza, F


    Platelet-related diseases correspond to functional defects or abnormal production (thrombopoiesis) of hereditary and immunological origins. Recent progress in the manipulation of the mouse genome (transgenesis, gene inactivation or insertion) has resulted in the generation of numerous strains exhibiting defective platelet function or production. Some strains reproduce known hereditary diseases affecting haemostasis (Glanzmann thrombasthenia, Bernard-Soulier syndrome (BSS) or thrombopoiesis (Wiscott-Aldrich or May-Hegglin syndrome). More often the mutated strains have no human equivalent and represent useful models to study: (i) the role of adhesive or signalling receptors or of signalling proteins in platelet-dependent haemostasis and thrombosis or; (ii) to study the poorly characterized mechanisms of thrombopoiesis, which implicate transcription factors (GATA, Fli1), growth factors and receptors (TPO, cMPL), and cytoskeletal or contractile proteins (tubulin, myosin). Additional mouse strains result from the selection of spontaneous mutants many of which affect intracellular platelet granules, representing models of storage pool diseases (SPD) such as the Gray platelet syndrome (alphaSPD) or Hermansky-Pudlack syndrome (deltaSPD). More recently, a systematic chemical mutagenesis approach has also identified genes involved in thrombopoiesis and platelet survival. Finally, mouse models of auto- or allo-immune thrombocytopenia have been developed to study the mechanisms of platelet destruction or removal.

  7. Platelet scintigraphy in atherothrombotic disease

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Yoshinari (Osaka National Hospital (Japan))


    Indium-111 platelet scintigraphy for the measurement of in vivo thrombogenicity is a useful noninvasive technique with a number of applications. From 1982 to 1989, we explored clinical relevance of this method for 576 consecutive patients with atherothrombotic disease. There was a disease-related difference in the percentage of positive platelet accumulation; 85% in patients with Dacron bifurcation graft, 75% in abdominal or thoracic aneurysm, 40% in intra-cardiac thrombi, 33% in arteriosclerosis obliterans and 25% in ischemic cerebrovascular disease. Labelled platelets accumulated frequently in the lesion with severe arteriographic abnormality. Aspirin clearly inhibited platelet accumulation on carotid atheroma but the effect of ticlopidine has been less conclusive. Short-term orally active PGI[sub 2] analogue had inhibitory effects on platelet accumulation in carotid atheroma and platelet aggregability, but did not cause significant reduction in plaque size. The results suggest the usefulness of platelet scintigraphy for monitoring the thrombogenicity in various atherothrombotic diseases. It will be necessary, however, to simplify the labelling procedures and to develop a new [sup 99m]Tc-labelled thrombus imaging agent, if thrombus imaging is to be considered for more generall use for patients with atherosclerosis. (author).

  8. Cyclosporine A enhances platelet aggregation. (United States)

    Grace, A A; Barradas, M A; Mikhailidis, D P; Jeremy, J Y; Moorhead, J F; Sweny, P; Dandona, P


    In view of the reported increase in thromboembolic episodes following cyclosporine A (CyA) therapy, the effect of this drug on platelet aggregation and thromboxane A2 release was investigated. The addition of CyA, at therapeutic concentrations to platelet rich plasma from normal subjects in vitro was found to increase aggregation in response to adrenaline, collagen and ADP. Ingestion of CyA by healthy volunteers was also associated with enhanced platelet aggregation. The CyA-mediated enhancement of aggregation was further enhanced by the addition in vitro of therapeutic concentrations of heparin. Platelets from renal allograft recipients treated with CyA also showed hyperaggregability and increased thromboxane A2 release, which were most marked at "peak" plasma CyA concentration and less so at "trough" concentrations. Platelet hyperaggregability in renal allograft patients on long-term CyA therapy tended to revert towards normal following the replacement of CyA with azathioprine. Hypertensive patients with renal allografts on nifedipine therapy had normal platelet function and thromboxane release in spite of CyA therapy. These observations suggest that CyA-mediated platelet activation may contribute to the pathogenesis of the thromboembolic phenomena associated with the use of this drug. The increased release of thromboxane A2 (a vasoconstrictor) may also play a role in mediating CyA-related nephrotoxicity.

  9. Matrix metalloproteinase-2 enhances platelet deposition on collagen under flow conditions. (United States)

    Guglielmini, Giuseppe; Appolloni, Viviana; Momi, Stefania; De Groot, Philip G; Battiston, Monica; De Marco, Luigi; Falcinelli, Emanuela; Gresele, Paolo


    Platelets contain and release matrix metalloproteinase-2 (MMP-2) that in turn potentiates platelet aggregation. Platelet deposition on a damaged vascular wall is the first, crucial, step leading to thrombosis. Little is known about the effects of MMP-2 on platelet activation and adhesion under flow conditions. We studied the effect of MMP-2 on shear-dependent platelet activation using the O'Brien filtration system, and on platelet deposition using a parallel-plate perfusion chamber. Preincubation of human whole blood with active MMP-2 (50 ng/ml, i.e. 0.78 nM) shortened filter closure time (from 51.8 ± 3.6 sec to 40 ± 2.7 sec, pMMP-2 inhibitor. High shear stress induced the release of MMP-2 from platelets, while TIMP-2 levels were not significantly reduced, therefore, the MMP-2/TIMP-2 ratio increased significantly showing enhanced MMP-2 activity. Preincubation of whole blood with active MMP-2 (0.5 to 50 ng/ml, i.e 0.0078 to 0.78 nM) increased dose-dependently human platelet deposition on collagen under high shear-rate flow conditions (3000 sec⁻¹) (maximum +47.0 ± 11.9%, pMMP-2 inhibitor reduced platelet deposition. In real-time microscopy studies, increased deposition of platelets on collagen induced by MMP-2 started 85 sec from the beginning of perfusion, and was abolished by a GPIIb/IIIa antagonist, while MMP-2 had no effect on platelet deposition on fibrinogen or VWF. Confocal microscopy showed that MMP-2 enhances thrombus volume (+20.0 ± 3.0% vs control) rather than adhesion. In conclusion, we show that MMP-2 potentiates shear-induced platelet activation by enhancing thrombus formation.

  10. Micro-array profiling exhibits remarkable intra-individual stability of human platelet micro-RNA. (United States)

    Stratz, C; Nührenberg, T G; Binder, H; Valina, C M; Trenk, D; Hochholzer, W; Neumann, F J; Fiebich, B L


    Platelets play an important role in haemostasis and thrombus formation. Latest research identified platelets harbouring so called microRNAs (miRNA). MiRNAs are short single-stranded RNAs modulating gene expression by targeting mRNAs. Limited data exist on inter-individual variability of platelet miRNA profile while no data are available on intra-individual variability. We assessed platelet miRNA profile in five volunteers at five time points over a time course of 10 days; 24 hours prior to the last blood sampling, subjects took 500 mg acetylsalicylic acid (ASA). Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma, and miRNA array-analysis was performed. Temporal patterns and ASA effect were explored by a linear mixed effects model for each miRNA. For the 20 most abundantly expressed platelet miRNAs, target gene search was performed and an annotation network was created. MiRNA expression profiling of 1,281 human miRNAs revealed relevant expression of 221 miRNAs consistently expressed in all samples at all time points. Correlation of platelet miRNA ranks was highly significant to other studies. Global distribution of miRNA expression was relatively similar in all subjects. No miRNA exhibited a significant effect of time at level 0.05. After 24 hours, no significant effect of ASA was found. Concerning functional implications of the 20 most abundantly expressed miRNAs, we found six functional themes. In conclusion, platelet miRNA profile is remarkably stable over the time period studied. Single-point analysis of platelet miRNA profile is reasonable when inter-individual differences are studied. The functional annotation network points toward extra-platelet effects of platelet miRNAs.

  11. Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation

    Directory of Open Access Journals (Sweden)

    Hou Ssu-Yu


    Full Text Available Abstract Background 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors (statins have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved. Methods The aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin. Results Simvastatin (20-50 μM exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin. Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2 formation, and phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP phosphorylation, and endothelial nitric oxide synthase (eNOS expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCγ2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation. Conclusion The most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP

  12. Report on electric cars and plug-in hybrid cars; Redegoerelse - elbiler og plug-in hybridbiler

    Energy Technology Data Exchange (ETDEWEB)

    Elkjaer Toennesen, A.; Winther, K.; Noerregaard, K. (Teknologisk Institut, Taastrup (Denmark)); Larsen, Esben; Christensen, Linda; Kveiborg, O. (Danmarks Teknologiske Univ., Kgs. Lyngby (DTU) (Denmark))


    The Center for Green Transport at the Danish Transport Authority has prepared this statement in order to uncover driving technical aspects, user expectations and needs, and the environmental consequences of using electric and plug-in hybrid cars. An electric car is defined as a car driven by an electric motor that has a battery that can be charged with power from the grid. A plug-in hybrid car is defined as a car that combines gasoline or diesel engine with an electric motor with a battery which can be recharged with power from the grid. From an overall consideration related to the transport sector electric cars and plug-in hybrid cars have the major advantage that negative impacts on environment and climate from traffic can be reduced while the high mobility is maintained. Through an increased use of electric cars and plug-in hybrid cars, the many advantages attached to the car as an individual transportation form is maintained, while CO{sub 2} emissions etc. are reduced. Electric cars and plug-in hybrid cars is one of the technologies that are considered to have particularly great prospects in the medium term when it comes to promoting new technologies in transport. Another advantage of using electric vehicles is the power supply factor. An increased use of electricity in transport will reduce the need for and dependence on fossil fuels in the sector. Both electric cars and plug-in hybrid cars are expected to be used for storage of wind power, a possibility which is hardly available today. The plug-in hybrid car could meet some of the challenges facing the pure electric car, because it also can use conventional fuel. The report presents analyses based on three focus areas: a) Users' needs, expectations and economics in relation to vehicles; b) The technology - and hence the manufacturers' opportunities and challenges; c) Connection to the power grid. (ln)

  13. Platelet enzyme abnormalities in leukemias

    Directory of Open Access Journals (Sweden)

    S Sharma


    Full Text Available Aim of the Study: The aim of this study was to evaluate platelet enzyme activity in cases of leukemia. Materials and Methods: Platelet enzymes glucose-6-phosphate dehydrogenase (G6PD, pyruvate kinase (PK and hexokinase (HK were studied in 47 patients of acute and chronic leukemia patients, 16 patients with acute myeloid leukemia (AML(13 relapse, three in remission, 12 patients with acute lymphocytic leukemia (ALL (five in relapse, seven in remission, 19 patients with chronic myeloid leukemia (CML. Results: The platelet G6PD activity was significantly low in cases of AML, ALL and also in CML. G6PD activity was normalized during AML remission. G6PD activity, although persistently low during ALL remission, increased significantly to near-normal during remission (P < 0.05 as compared with relapse (P < 0.01. Platelet PK activity was high during AML relapse (P < 0.05, which was normalized during remission. Platelet HK however was found to be decreased during all remission (P < 0.05. There was a significant positive correlation between G6PD and PK in cases of AML (P < 0.001 but not in ALL and CML. G6PD activity did not correlate with HK activity in any of the leukemic groups. A significant positive correlation was however seen between PK and HK activity in cases of ALL remission (P < 0.01 and CML (P < 0.05. Conclusions: Both red cell and platelet enzymes were studied in 36 leukemic patients and there was no statistically significant correlation between red cell and platelet enzymes. Platelet enzyme defect in leukemias suggests the inherent abnormality in megakaryopoiesis and would explain the functional platelet defects in leukemias.

  14. Plug-in electric vehicles integrating fluctuating renewable electricity

    Energy Technology Data Exchange (ETDEWEB)

    Dallinger, David


    This paper examines a method to model plug-in electric vehicles as part of the power system and presents results for the contribution of plug-in electric vehicles to balance the fluctuating electricity generation of renewable energy sources. The scientific contribution includes: - A novel approach to characterizing fluctuating generation. This allows the detailed comparison of results from energy analysis and is the basis to describe the effect of electricity from renewable energy sources and plug-in electric vehicles on the power system. - The characterization of mobile storage, which includes the description of mobility behavior using probabilities and battery discharging costs. - The introduction of an agent-based simulation approach, coupling energy markets and distributed grids using a price-based mechanism design. - The description of an agent with specific driving behavior, battery discharging costs and optimization algorithm suitable for real plug-in vehicles and simulation models. - A case study for a 2030 scenario describing the contribution of plug-in electric vehicles to balance generation from renewable energy sources in California and Germany.

  15. Damage Tolerance Assessment of Friction Pull Plug Welds (United States)

    McGill, Preston; Burkholder, Jonathan


    Friction stir welding is a solid state welding process developed and patented by The Welding Institute in Cambridge, England. Friction stir welding has been implemented in the aerospace industry in the fabrication of longitudinal welds in pressurized cryogenic propellant tanks. As the industry looks to implement friction stir welding in circumferential welds in pressurized cryogenic propellant tanks, techniques to close out the termination hole associated with retracting the pin tool are being evaluated. Friction pull plug welding is under development as a one means of closing out the termination hole. A friction pull plug weld placed in a friction stir weld results in a non-homogenous weld joint where the initial weld, plug weld, their respective heat affected zones and the base metal all interact. The welded joint is a composite, plastically deformed material system with a complex residual stress field. In order to address damage tolerance concerns associated with friction plug welds in safety critical structures, such as propellant tanks, nondestructive inspection and proof testing may be required to screen hardware for mission critical defects. The efficacy of the nondestructive evaluation or the proof test is based on an assessment of the critical flaw size in the test or service environments. Test data relating residual strength capability to flaw size in two aluminum alloy friction plug weld configurations is presented.

  16. Platelet surface glutathione reductase-like activity. (United States)

    Essex, David W; Li, Mengru; Feinman, Richard D; Miller, Anna


    We previously found that reduced glutathione (GSH) or a mixture of GSH/glutathione disulfide (GSSG) potentiated platelet aggregation. We here report that GSSG, when added to platelets alone, also potentiates platelet aggregation. Most of the GSSG was converted to GSH by a flavoprotein-dependent platelet surface mechanism. This provided an appropriate redox potential for platelet activation. The addition of GSSG to platelets generated sulfhydryls in the beta subunit of the alpha(IIb)beta(3) fibrinogen receptor, suggesting a mechanism for facilitation of agonist-induced platelet activation.

  17. Platelet P2Y12 is involved in murine pulmonary metastasis.

    Directory of Open Access Journals (Sweden)

    Yanhua Wang

    Full Text Available The involvement of platelets in tumor progression is well recognized. The depletion of circulating platelets or pharmacologic inhibitors of platelet activation decreases the metastatic potential of circulating tumor cells in metastasis mouse models. The platelet ADP receptor P2Y12 amplifies the initial hemostatic responses activated by a variety of platelet agonists and stabilizes platelet aggregation, playing a crucial role in granule secretion, integrin activation and thrombus formation. However, the relationship between P2Y12 and tumor progression is not clear. In our study, the Lewis Lung Carcinoma (LLC spontaneous metastatic mouse model was used to evaluate the role of P2Y12 in metastasis. The results demonstrated that P2Y12 deficiency significantly reduced pulmonary metastasis. Further studies indicated that P2Y12 deficiency diminished the ability of LLC cells to induce platelet shape change and release of active TGFβ1 by a non-contact dependent mechanism resulting in a diminished, platelet-induced EMT-like transformation of the LLC cells, and that transformation probably is a prerequisite of LLC cell metastasis. Immunohistochemical analyses indicated an obvious P2Y12 deficiency related attenuation of recruitment of VEGFR1+ bone marrow derived cell clusters, and extracellular matrix fibronectin deposition in lungs, which presumably are required for pre-metastatic niche formation. In contrast to the LLC cells, non-epithelial melanoma B16 cells induced platelet aggregation in a cell number and P2Y12-dependent manner. Also, a platelet induced EMT-like transformation of B16 cells is dependent on P2Y12. In agreement with the LLC cell model, platelet P2Y12 deficiency also results in significantly less lung metastasis in the B16 melanoma experimental metastasis model. These results demonstrate that P2Y12 is a safe drug target for anti-thrombotic therapy, and that P2Y12 may serve as a new target for inhibition of tumor metastasis.

  18. Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

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    Trevor P. Fidler


    Full Text Available Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT 1 and GLUT3 (double knockout [DKO] specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes, including Ca2+ signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets, with circulating counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an essential role for energy metabolism in platelet viability. Thus, substrate metabolism is essential for platelet production, activation, and survival.

  19. Contribution of blood platelets to vascular pathology in Alzheimer's disease

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    Zhang W


    Full Text Available Wei Zhang,1,2 Wei Huang,1 Fang Jing11Department of Pharmacology, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People's Republic of China; 2Shanghai Engineering Research Center of Molecular Therapy and Pharmaceutical Innovation, Shanghai, People's Republic of ChinaAbstract: Cerebral amyloid angiopathy (CAA is a critical factor in the pathogenesis of Alzheimer's disease (AD. In the clinical setting, nearly 98% AD patients have CAA, and 75% of these patients are rated as severe CAA. It is characterized by the deposition of the β-amyloid peptide (mainly Aβ40 in the walls of cerebral vessels, which induces the degeneration of vessel wall components, reduces cerebral blood flow, and aggravates cognitive decline. Platelets are anuclear cell fragments from bone marrow megakaryocytes and their function in hemostasis and thrombosis has long been recognized. Recently, increasing evidence suggests that platelet activation can also mediate the onset and development of CAA. First, platelet activation and adhesion to a vessel wall is the initial step of vascular injury. Activated platelets contribute to more than 90% circulating Aß (mainly Aβ1-40, which in turn activates platelets and results in the vicious cycle of Aβ overproduction in damaged vessel. Second, the uncontrolled activation of platelets leads to a chronic inflammatory reaction by secretion of chemokines (eg, platelet factor 4 [PF4], regulated upon activation normal T-cell expressed and presumably secreted [RANTES], and macrophage inflammatory protein [MIP-1α], interleukins (IL-1 β, IL-7, and IL-8, prostaglandins, and CD40 ligand (CD40L. The interaction of these biological response modulators with platelets, endothelial cells, and leukocytes establishes a localized inflammatory response that contributes to CAA formation. Finally, activated platelets are the upholder of fibrin clots, which are structurally abnormal and resistant to degradation

  20. Mechanisms of platelet-mediated liver regeneration. (United States)

    Lisman, Ton; Porte, Robert J


    Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.

  1. Platelets as delivery systems for disease treatments


    Shi, Qizhen; Montgomery, Robert R.


    Platelets are small, anucleate, discoid shaped blood cells that play a fundamental role in hemostasis. Platelets contain a large number of biologically active molecules within cytoplasmic granules that are critical to normal platelet function. Because platelets circulate in blood through out the body, release biological molecules and mediators on demand, and participate in hemostasis as well as many other pathophysiologic processes, targeting expression of proteins of interest to platelets an...

  2. Evaluation of the TEG® platelet mapping™ assay in blood donors

    Directory of Open Access Journals (Sweden)

    Steinbrüchel Daniel A


    Full Text Available Abstract Background Monitoring of antiplatelet therapy in patients at cardiovascular risk is difficult because existing platelet function tests are too sophisticated for clinical routine. The whole blood TEG® Platelet Mapping™ assay measures clot strength as maximal amplitude (MA and enables for quantification of platelet function, including the contribution of the adenosine diphosphate (ADP and thromboxane A2 (TxA2 receptors to clot formation. Methods In 43 healthy blood donors, the analytical (CVa and inter-individual variability (CVg of the TEG® Platelet Mapping™ assay were determined together with platelet receptor inhibition in response to arachidonic acid (AA and ADP. Results The CVa of the assay for maximal platelet contribution to clot strength (MAThrombin was 3.5%, for the fibrin contribution to clot strength (MAFibrin 5.2%, for MAAA 4.5% and for MAADP it was 6.6%. The MAThrombin CVg was 2.8%, MAFibrin 4.7%, MAAA 6.6% and for MAADP it was 26.2%. Females had a higher MAThrombin compared to males (62.8 vs. 58.4 mm, p = 0.005. The platelet TxA2 receptor inhibition was 1.2% (range 0–10% and lower than for the ADP receptor (18.6% (0–58%; p Conclusion The high variability in ADP receptor inhibition may explain both the differences in response to ADP receptor inhibitor therapy and why major bleeding sometimes develops during surgery in patients not treated with ADP receptor inhibitors. An analytical variation of ~5 % for the TEG® enables, however, for routine monitoring of the variability in ADP receptor inhibition and of antiplatelet therapy.

  3. Flexible Plug Repair for Shuttle Wing Leading Edge (United States)

    Camarda, Charles J.; Sikora, Joseph; Smith, Russel; Rivers, H.; Scotti, Stephen J.; Fuller, Alan M.; Klacka, Robert; Reinders, Martin; Schwind, Francis; Sullivan, Brian; hide


    In response to the Columbia Accident Investigation Board report, a plug repair kit has been developed to enable astronauts to repair the space shuttle's wing leading edge (WLE) during orbit. The plug repair kit consists of several 17.78- cm-diameter carbon/silicon carbide (C/SiC) cover plates of various curvatures that can be attached to the refractory carbon-carbon WLE panels using a TZM refractory metal attach mechanism. The attach mechanism is inserted through the damage in the WLE panel and, as it is tightened, the cover plate flexes to conform to the curvature of the WLE panel within 0.050 mm. An astronaut installs the repair during an extravehicular activity (EVA). After installing the plug repair, edge gaps are checked and the perimeter of the repair is sealed using a proprietary material, developed to fill cracks and small holes in the WLE.

  4. Susceptibility-matched plugs for microcoil NMR probes (United States)

    Kc, Ravi; Gowda, Yashas N.; Djukovic, Danijel; Henry, Ian D.; Park, Gregory H. J.; Raftery, Daniel


    For mass-limited samples, the residual sample volume outside the detection coil is an important concern, as is good base line resolution. Here, we present the construction and evaluation of magnetic susceptibility-matched plugs for microcoil NMR sample cells which address these issues. Mixed-epoxy glue and ultem tube plugs that have susceptibility values close to those of perfluorocarbon FC-43 (fluorinert) and copper were used in small volume (0.5-2 μL) and larger volume (15-20 μL) thin glass capillary sample cells. Using these plugs, the sample volume efficiency (i.e. ratio of active volume to total sample volume in the microcoil NMR cell) was improved by 6-12-fold without sensitivity and resolution trade-offs. Comparison with laser etched or heat etched microcoil sample cells is provided. The approaches described are potentially useful in metabolomics for biomarkers detection in mass limited biological samples.

  5. Reliability assessment of reserved water disposal with erodible fuse plug

    Directory of Open Access Journals (Sweden)

    Kosichenko Yuriy Mikhaylovich

    Full Text Available Water disposal constructions are one of the most responsible constructions of reservoir hydrosystem, that’s why the a lot of attention was always paid to the problems of estimating and providing their reliability and safety. The most important function of such objects is providing reliability and safety of other hydraulic constructions and economic assets in afterbay and water head. The authors offer estimation method for reliability and faultless performance of reserved water disposal with erodible fuse plug on low-head water development. In order to estimate the reliability of reserved water disposal with erodible fuse plug the Bayesian treatment was used. The calculation of diagnoses (states of reserved water disposal isoffered in case of diagnostic properties k 1 and k 2. One of the main demands placed onreserved water disposals is erosion of soil plug in case of flood discharge exeedance over the estimated frequency with the full opening of the waste sluice.

  6. Susceptibility-matched plugs for microcoil NMR probes. (United States)

    Kc, Ravi; Gowda, Yashas N; Djukovic, Danijel; Henry, Ian D; Park, Gregory H J; Raftery, Daniel


    For mass-limited samples, the residual sample volume outside the detection coil is an important concern, as is good base line resolution. Here, we present the construction and evaluation of magnetic susceptibility-matched plugs for microcoil NMR sample cells which address these issues. Mixed-epoxy glue and ultem tube plugs that have susceptibility values close to those of perfluorocarbon FC-43 (fluorinert) and copper were used in small volume (0.5-2 microL) and larger volume (15-20 microL) thin glass capillary sample cells. Using these plugs, the sample volume efficiency (i.e. ratio of active volume to total sample volume in the microcoil NMR cell) was improved by 6-12-fold without sensitivity and resolution trade-offs. Comparison with laser etched or heat etched microcoil sample cells is provided. The approaches described are potentially useful in metabolomics for biomarkers detection in mass limited biological samples.

  7. [Protein kinase C activation induces platelet apoptosis]. (United States)

    Zhao, Li-Li; Chen, Meng-Xing; Zhang, Ming-Yi; Dai, Ke-Sheng


    Platelet apoptosis elucidated by either physical or chemical compound or platelet storage occurs wildly, which might play important roles in controlling the numbers and functions of circulated platelets, or in the development of some platelet-related diseases. However, up to now, a little is known about the regulatory mechanisms of platelet apoptosis. Protein kinase C (PKC) is highly expressed in platelets and plays central roles in regulating platelet functions. Although there is evidence indicating that PKC is involved in the regulation of apoptosis of nucleated cells, it is still unclear whether PKC plays a role in platelet apoptosis. The aim of this study was to investigate the role of PKC in platelet apoptosis. The effects of PKC on mitochondrial membrane potential (ΔΨm), phosphatidylserine (PS) exposure, and caspase-3 activation of platelets were analyzed by flow cytometry and Western blot. The results showed that the ΔΨm depolarization in platelets was induced by PKC activator in time-dependent manner, and the caspase-3 activation in platelets was induced by PKC in concentration-dependent manner. However, the platelets incubated with PKC inhibitor did not results in ΔΨm depolarization and PS exposure. It is concluded that the PKC activation induces platelet apoptosis through influencing the mitochondrial functions and activating caspase 3. The finds suggest a novel mechanism for PKC in regulating platelet numbers and functions, which has important pathophysiological implications for thrombosis and hemostasis.

  8. Eddy Current Minimizing Flow Plug for Use in Flow Conditioning and Flow Metering (United States)

    England, John Dwight (Inventor); Kelley, Anthony R. (Inventor)


    An eddy-current-minimizing flow plug has open flow channels formed between the plug's inlet and outlet. Each open flow channel includes (i) a first portion that originates at the inlet face and converges to a location within the plug that is downstream of the inlet, and (ii) a second portion that originates within the plug and diverges to the outlet. The diverging second portion is approximately twice the length of the converging first portion. The plug is devoid of planar surface regions at its inlet and outlet, and in fluid flow planes of the plug that are perpendicular to the given direction of a fluid flowing therethrough.

  9. Varying nanoparticle pseudostationary phase plug length during capillary electrophoresis† (United States)

    Subramaniam, Varuni; Griffith, Lindsay; Haes, Amanda J.


    Capillary electrophoresis based separations of the hypothesized Parkinson’s disease biomarkers dopamine, epinephrine, pyrocatechol, L-3,4-dihydroxyphenylalanine (L-DOPA), glutathione, and uric acid are performed in the presence of a 1 nM 11-mercaptoundecanoic acid functionalized gold (Au@MUA) nanoparticle pseudostationary phase plug. Au@MUA nanoparticles are monitored in the capillary and remain stable in the presence of electrically-driven flow. Migration times, peak areas, and relative velocity changes (vs. no pseudostationary) are monitored upon varying (1) the Au@MUA nanoparticle pseudostationary phase plug length at a fixed separation voltage and (2) the separation voltage for a fixed Au@MUA nanoparticle pseudostationary phase plug length. For instance, the migration times of positively charged dopamine and epinephrine increase slightly as the nanoparticle pseudostationary phase plug length increases with concomitant decreases in peak areas and relative velocities as a result of attractive forces between the positively charged analytes and the negatively charged nanoparticles. Migration times for neutral pyrocatechol and slightly negative L-DOPA did not exhibit significant changes with increasing nanoparticle pseudostationary plug length; however, reduction in peak areas for these two molecules were evident and attributed to non-specific interactions (i.e. hydrogen bonding and van der Waals interactions) between the biomarkers and nanoparticles. Moreover, negatively charged uric acid and glutathione displayed progressively decreasing migration times and peak areas and as a result, increased relative velocities with increasing nanoparticle pseudostationary phase plug length. These trends are attributed to partitioning and exchanging with 11-mercaptoundecanoic acid on nanoparticle surfaces for uric acid and glutathione, respectively. Similar trends are observed when the separation voltage decreased thereby suggesting that nanoparticle-biomarker interaction

  10. Plug and Play PV Systems for American Homes

    Energy Technology Data Exchange (ETDEWEB)

    Hoepfner, Christian [Fraunhofer USA, Inc., Boston, MA (United States)


    The core objectives of the Plug & Play PV Systems Project were to develop a PV system that can be installed on a residential rooftop for less than $1.50/W in 2020, and in less than 10 hours (from point of purchase to commissioning). The Fraunhofer CSE team’s approach to this challenge involved a holistic approach to system design – hardware and software – that make Plug & Play PV systems: • Quick, easy, and safe to install • Easy to demonstrate as code compliant • Permitted, inspected, and interconnected via an electronic process Throughout the three years of work during this Department of Energy SunShot funded project, the team engaged in a substantive way with inspectional services departments and utilities, manufacturers, installers, and distributors. We received iterative feedback on the system design and on ideas for how such systems can be commercialized. This ultimately led us to conceiving of Plug & Play PV Systems as a framework, with a variety of components compatible with the Plug & Play PV approach, including string or microinverters, conventional modules or emerging lightweight modules. The framework enables a broad group of manufacturers to participate in taking Plug & Play PV Systems to market, and increases the market size for such systems. Key aspects of the development effort centered on the system hardware and associated engineering work, the development of a Plug & Play PV Server to enable the electronic permitting, inspection and interconnection process, understanding the details of code compliance and, on occasion, supporting applications for modifications to the code to allow lightweight modules, for example. We have published a number of papers on our testing and assessment of novel technologies (e.g., adhered lightweight modules) and on the electronic architecture.

  11. Versatile Friction Stir Welding/Friction Plug Welding System (United States)

    Carter, Robert


    A proposed system of tooling, machinery, and control equipment would be capable of performing any of several friction stir welding (FSW) and friction plug welding (FPW) operations. These operations would include the following: Basic FSW; FSW with automated manipulation of the length of the pin tool in real time [the so-called auto-adjustable pin-tool (APT) capability]; Self-reacting FSW (SRFSW); SR-FSW with APT capability and/or real-time adjustment of the distance between the front and back shoulders; and Friction plug welding (FPW) [more specifically, friction push plug welding] or friction pull plug welding (FPPW) to close out the keyhole of, or to repair, an FSW or SR-FSW weld. Prior FSW and FPW systems have been capable of performing one or two of these operations, but none has thus far been capable of performing all of them. The proposed system would include a common tool that would have APT capability for both basic FSW and SR-FSW. Such a tool was described in Tool for Two Types of Friction Stir Welding (MFS- 31647-1), NASA Tech Briefs, Vol. 30, No. 10 (October 2006), page 70. Going beyond what was reported in the cited previous article, the common tool could be used in conjunction with a plug welding head to perform FPW or FPPW. Alternatively, the plug welding head could be integrated, along with the common tool, into a FSW head that would be capable of all of the aforementioned FSW and FPW operations. Any FSW or FPW operation could be performed under any combination of position and/or force control.

  12. A physical description of the adhesion and aggregation of platelets

    CERN Document Server

    Chopard, Bastien; Latt, Jonas; Dubois, Frank; Yourassowsky, Catherine; Van Antwerpen, Pierre; Eker, Omer; Vanhamme, Luc; Perez-Morga, David; Courbebaisse, Guy; Boudjeltia, Karim Zouaoui


    The early stages of clot formation in blood vessels involve platelets adhesion-aggregation. Although these mechanisms have been extensively studied, gaps in their understanding still persist. We have performed detailed in-vitro experiments and developed a numerical model to better describe and understand this phenomenon. Unlike previous studies, we took into account both activated and non-activated platelets, as well as the 3D nature of the aggregation process. Our investigation reveals that blood albumin is a major parameter limiting platelet adhesion and aggregation. Our results also show that the well accepted Zydney-Colton shear-induced diffusivity is much too low to explain the observed deposition rate. Simulations are in very good agreement with observations and provide quantitative estimates of the adhesion and aggregation rates that are hard to measure experimentally.

  13. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features. (United States)

    Dohan, David M; Choukroun, Joseph; Diss, Antoine; Dohan, Steve L; Dohan, Anthony J J; Mouhyi, Jaafar; Gogly, Bruno


    Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this second article, we investigate the platelet-associated features of this biomaterial. During PRF processing by centrifugation, platelets are activated and their massive degranulation implies a very significant cytokine release. Concentrated platelet-rich plasma platelet cytokines have already been quantified in many technologic configurations. To carry out a comparative study, we therefore undertook to quantify PDGF-BB, TGFbeta-1, and IGF-I within PPP (platelet-poor plasma) supernatant and PRF clot exudate serum. These initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrin meshes. This result would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibrin matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.

  14. Warning: safety risk with some Apple AC Wall Plug Adapters

    CERN Multimedia

    CERN IT department


    Dear Mac and iOS Users, Apple has determined that some of its two prong Apple AC wall plug adapters may break and create a risk of electrical shock.   CERN users can now exchange their affected Apple wall plug adapters at the Service Desk. To find out if your adapter is affected and for any further information concerning the procedure to follow to exchange it, please check the following URL:

  15. Implantation of the AMPLATZER™ Cardiac Plug: tips and tricks. (United States)

    Park, Jai-Wun


    The AMPLATZER™ Cardiac Plug device is designed for percutaneous occlusion of the left atrial appendage (LAA) for stroke prophylaxis in patients with atrial fibrillation (AF) who are contraindicated or intolerant to oral anticoagulation. While updated guidelines start to refer to this therapy (Camm A, Eur Heart J, doi:10.1093/eurheartj/ehs253, 2012) and operators gain experience with this relatively new technique, continuing efforts are focused on maximizing the safety of the implantation procedure. This paper is aimed at explaining and illustrating the distinct steps and specific considerations related to the implantation of the AMPLATZER™ Cardiac Plug.

  16. Platelet-containing tantalum powders

    Energy Technology Data Exchange (ETDEWEB)

    Schiele, E.K.


    A method of forming platelet tantalum powders is described comprising the steps of: (a) providing an ingot-derived precursor tantalum powder, and (b) ball-milling the precursor powder for a time sufficient to form a platelet powder having an average FSSS of less than about 2 micrometers, a Scott density not greater than about 30 g/in/sup 3/ and a BET surface area of at least about 0.7 in/sup 2//g.

  17. Plug into PR. NJLA Public Relations Handbook. (United States)

    New Jersey Library Association, Trenton.

    A guide to using public relations techniques to promote both everyday services and special events at libraries, this handbook describes and suggests ways to use library displays; in-house printing; the local media, e.g., radio spots and cable television; library programs; marketing and promotion; and fundraising, including the formation of a…

  18. Helenalin and 11 alpha,13-dihydrohelenalin, two constituents from Arnica montana L., inhibit human platelet function via thiol-dependent pathways. (United States)

    Schröder, H; Lösche, W; Strobach, H; Leven, W; Willuhn, G; Till, U; Schrör, K


    This study investigates the effect on human platelet function of two sesquiterpene lactones from Arnica montana L., helenalin (H) and 11 alpha,13-dihydrohelenalin (DH). Both compounds inhibited collagen-induced platelet aggregation, thromboxane formation and 5-hydroxytryptamine secretion in a concentration-dependent manner at 3-300 microM. When arachidonic acid was used as stimulus, thromboxane formation remained unaffected despite of inhibition of platelet aggregation. Both H and DH reduced the number of acid-soluble sulfhydryl groups in platelets, by up to 78% at anti-aggregatory concentrations. Moreover, H- and DH-induced platelet inhibition could be prevented by the thiol containing amino acid cysteine. It is concluded that H and DH inhibit platelet function via interaction with platelet sulfhydryl groups, probably associated with reduced phospholipase A2 activity.

  19. PLUG: A FORTRAN program for the analysis of PLUG flow reactors with gas-phase and surface chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Larson, R.S.


    This manual describes the structure and usage of the computer program PLUG, which simulates the behavior of plug flow chemical reactors. More specifically, the code is designed to model the non-dispersive one-dimensional flow of a chemically reacting ideal gas mixture in a conduit of essentially arbitrary geometry. The code makes use of the CHEMKIN and SURFACE CHEMKIN software packages to handle gas-phase and heterogeneous kinetics as well as thermodynamic properties. In addition, the standard implicit code DASSL is used to solve the set of differential/algebraic equations describing the reactor. These equations are briefly discussed here, after which the procedures for running PLUG are described in some detail. Input and output files for a sample problem involving chemical vapor deposition are given.

  20. In vitro function of random donor platelets stored for 7 days in composol platelet additive solution

    Directory of Open Access Journals (Sweden)

    Gupta Ashish


    Full Text Available Background and Aim: Platelets are routinely isolated from whole blood and stored in plasma for 5 days. The present study was done to assess the in vitro function of random donor platelets stored for 7 days in composol platelet additive solution at 22°C. Materials and Methods: The study sample included 30 blood donors of both sex in State Blood Bank, CSM Medical University, Lucknow. Random donor platelets were prepared by platelet rich plasma method. Whole blood (350 ml was collected in anticoagulant Citrate Phosphate Dextrose Adenine triple blood bags. Random donor platelets were stored for 7 days at 22°C in platelet incubators and agitators, with and without additive solution. Results: Platelet swirling was present in all the units at 22°C on day 7, with no evidence of bacterial contamination. Comparison of the mean values of platelet count, platelet factor 3, lactate dehydrogenase, pH, glucose and platelet aggregation showed no significant difference in additive solution, whereas platelet factor 3, glucose and platelet aggregation showed significant difference (P < 0.001 on day 7 without additive solution at 22°C. Conclusion: Our study infers that platelet viability and aggregation were best maintained within normal levels on day 7 of storage in platelet additive solution at 22°C. Thus, we may conclude that in vitro storage of random donor platelets with an extended shelf life of 7 days using platelet additive solution may be advocated to improve the inventory of platelets.

  1. Amarogentin, a Secoiridoid Glycoside, Abrogates Platelet Activation through PLCγ2-PKC and MAPK Pathways

    Directory of Open Access Journals (Sweden)

    Ting-Lin Yen


    Full Text Available Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60 μM inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (MAPKs. It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLCγ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

  2. Evidence of platelet activation in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Alexander J Steven


    Full Text Available Abstract Objective A fatality in one multiple sclerosis (MS patient due to acute idiopathic thrombocytopenic purpura (ITP and a near fatality in another stimulated our interest in platelet function abnormalities in MS. Previously, we presented evidence of platelet activation in a small cohort of treatment-naive MS patients. Methods In this report, 92 normal controls and 33 stable, untreated MS patients were studied. Platelet counts, measures of platelet activation [plasma platelet microparticles (PMP, P-selectin expression (CD62p, circulating platelet microaggragtes (PAg], as well as platelet-associated IgG/IgM, were carried out. In addition, plasma protein S activity was measured. Results Compared to controls, PMP were significantly elevated in MS (p Conclusion Platelets are significantly activated in MS patients. The mechanisms underlying this activation and its significance to MS are unknown. Additional study of platelet activation and function in MS patients is warranted.

  3. Inhibitory effect of GBH on platelet aggregation through inhibition of intracellular Ca2+ mobilization in activated human platelets. (United States)

    Park, Won-Hwan; Kim, Han-Kyu; Nam, Kyung-Soo; Shon, Yun-Hee; Jeon, Byung Hun; Moon, Sung-Kwon; Kim, Min-Gon; Kim, Cheorl-Ho


    Geiji-Bokryung-Hwan (GBH) was studied on antiplatelet activity in human platelet suspensions. GBH consists of the 5 herbs Cinnamomi Ramulus, Poria Cocos, Mountan Cortex Radicis, Paeoniae Radix, and Persicae Semen, which have been used in herbal medicine for thousands of years for atherosclerosis. The mechanism involved in the antiplatelet activity of GBH in human platelet suspensions was investigated. GBH inhibited platelet aggregation and Ca2+ mobilization in a concentration-dependent manner without increasing intracellular cyclic AMP and cyclic GMP. GBH had no inhibitory effect on thromboxane B2 (TXB2) production in cell-free systems. Collagen-related peptide (CRP)-induced Ca2+ mobilization is regulated by phospholipase C-2 (PLC-gamma2) activation. We evaluated the effect of GBH on tyrosine phosphorylation of PLC-gamma2 and the production of inositol-1,4,5-trisphosphate (IP3). GBH at concentrations that inhibited platelet aggregation and Ca2+ mobilization had no effects on tyrosine phosphorylation of PLC-gamma2 or on the formation of IP3 induced by CRP. Similar results were obtained with thrombin-induced platelet activation. GBH inhibited platelet aggregation and Ca2+ mobilization induced by thrombin without affecting the production of IP3. We then evaluated the effect of GBH on the binding of IP3 to its receptor. GBH at high concentrations partially blocked the binding of IP3 to its receptor. Therefore, the results suggested that GBH suppresses Ca2+ mobilization at a step distal to IP3 formation. GBH may provide a good tool for investigating Ca2+ mobilization.

  4. Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion. (United States)

    Feghhi, Shirin; Munday, Adam D; Tooley, Wes W; Rajsekar, Shreya; Fura, Adriane M; Kulman, John D; López, Jose A; Sniadecki, Nathan J


    Platelets bind to exposed vascular matrix at a wound site through a highly specialized surface receptor, glycoprotein (GP) Ib-IX-V complex, which recognizes von Willebrand factor (VWF) in the matrix. GPIb-IX-V is a catch bond for it becomes more stable as force is applied to it. After attaching to the wound site, platelets generate cytoskeletal forces to compact and reinforce the hemostatic plug. Here, we evaluated the role of the GPIb-IX-V complex in the transmission of cytoskeletal forces. We used arrays of flexible, silicone nanoposts to measure the contractility of individual platelets on VWF. We found that a significant proportion of cytoskeletal forces were transmitted to VWF through GPIb-IX-V, an unexpected finding given the widely held notion that platelet forces are transmitted exclusively through its integrins. In particular, we found that the interaction between GPIbα and the A1 domain of VWF mediates this force transmission. We also demonstrate that the binding interaction between GPIbα and filamin A is involved in force transmission. Furthermore, our studies suggest that cytoskeletal forces acting through GPIbα are involved in maintaining platelet adhesion when external forces are absent. Thus, the GPIb-IX-V/VWF bond is able to transmit force, and uses this force to strengthen the bond through a catch-bond mechanism. This finding expands our understanding of how platelets attach to sites of vascular injury, describing a new, to the best of our knowledge, mechanism in which the catch bonds of GPIb-IX-V/VWF can be supported by internal forces produced by cytoskeletal tension.

  5. Unique morphology and gradient arrangement of nacre's platelets in green mussel shells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jun; Zhang, Gangsheng, E-mail:


    Nacre has long served as a classic model in biomineralization and the synthesis of biomimetic materials. However, the morphology and arrangement of its basic building blocks, the aragonite platelets, are still under hot debate. In this study, using a field emission scanning electron microscope (SEM), a high-resolution transmission electron microscope (HRTEM), and an X-ray diffractometer (XRD), we investigate the platelets at the edges and centers of green mussel shells. We find that 1) flat and curved platelets coexist in green mussel shells; 2) the immature platelets at the shell edge are aggregates of aragonite nanoparticles, whereas the immature ones at the shell center are single crystals; and 3) the morphology and thickness of the platelets exhibit a gradient arrangement. Based on these findings, we hypothesize that the gradient in the thickness and curvature of the platelets may probably result from the difference in growth rate between the edge and the center of the shell and from the gradient in compressive stress imposed by the closing of the shells by the adductor muscles or the withdrawal of the periostracum by the mantle. We expect that the presented results will shed new light on the formation mechanisms of natural composite materials. - Highlights: • Flat and curved platelets coexist in green mussel shells. • The immature platelets at the shell edge consist of aragonite nanoparticles. • The immature platelets at the shell center are single crystals. • The morphology and thickness of platelets exhibit a gradient arrangement. • The gradient arrangement of platelets may result from the stress gradient.

  6. Restoration of responsiveness of phospholipase Cγ2-deficient platelets by enforced expression of phospholipase Cγ1.

    Directory of Open Access Journals (Sweden)

    Yongwei Zheng

    Full Text Available Receptor-mediated platelet activation requires phospholipase C (PLC activity to elevate intracellular calcium and induce actin cytoskeleton reorganization. PLCs are classified into structurally distinct β, γ, δ, ε, ζ, and η isoforms. There are two PLCγ isoforms (PLCγ1, PLCγ2, which are critical for activation by tyrosine kinase-dependent receptors. Platelets express both PLCγ1 and PLCγ2. Although PLCγ2 has been shown to play a dominant role in platelet activation, the extent to which PLCγ1 contributes has not been evaluated. To ascertain the relative contributions of PLCγ1 and PLCγ2 to platelet activation, we generated conditionally PLCγ1-deficient, wild-type (WT, PLCγ2-deficient, and PLCγ1/PLCγ2 double-deficient mice and measured the ability of platelets to respond to different agonists. We found that PLCγ2 deficiency abrogated αIIbβ3-dependent platelet spreading, GPVI-dependent platelet aggregation, and thrombus formation on collagen-coated surfaces under shear conditions, which is dependent on both GPVI and αIIbβ3. Addition of exogenous ADP overcame defective spreading of PLCγ2-deficient platelets on immobilized fibrinogen, suggesting that PLCγ2 is required for granule secretion in response to αIIbβ3 ligation. Consistently, αIIbβ3-mediated release of granule contents was impaired in the absence of PLCγ2. In contrast, PLCγ1-deficient platelets spread and released granule contents normally on fibrinogen, exhibited normal levels of GPVI-dependent aggregation, and formed thrombi normally on collagen-coated surfaces. Interestingly, enforced expression of PLCγ1 fully restored GPVI-dependent aggregation and αIIbβ3-dependent spreading of PLCγ2-deficient platelets. We conclude that platelet activation through GPVI and αIIbβ3 utilizes PLCγ2 because PLCγ1 levels are insufficient to support responsiveness, but that PLCγ1 can restore responsiveness if expressed at levels normally achieved by PLCγ2.

  7. Plug-In Electric Vehicle Handbook for Fleet Managers (Brochure)

    Energy Technology Data Exchange (ETDEWEB)


    Plug-in electric vehicles (PEVs) are entering the automobile market and are viable alternatives to conventional vehicles. This guide for fleet managers describes the basics of PEV technology, PEV benefits for fleets, how to select the right PEV, charging a PEV, and PEV maintenance.


    Directory of Open Access Journals (Sweden)



    Full Text Available In spite of existence of many standard security mechanisms for ensuring secure e- Commerce business, users still fall prey for onlin e attacks. One such simple but powerful attack is ‘Phishing’. Phishing is the most alarming threat in the e-Commerce world and effective anti-phishing technique is the need of the hour. This paper focuses on a novel anti-phishing browser plug-in which uses information hiding technique - Steganography. A Robust Message based Image Steganography (RMIS algorithm has been proposed. The same has been incorporated in the form of a browser plug-in (safari called Pixastic. Pixastic is tested in an online banking scenario and it is compared with other well-known anti-phishing plug-in methods in practice. Various parameters such as robustness, usability and its behavior on various attacks have been analysed. From experimental results, it is ev ident that our method Pixastic performs well compared to other anti-phishing plug-ins.

  9. Nuclear determination of saturation profiles in core plugs. Status report

    Energy Technology Data Exchange (ETDEWEB)

    Sletsgaard, J. [DTU, Inst. for Automation (Denmark)


    A method to determine liquid saturations in core plugs during flooding is of importance when the relative permeability and capillary pressure function are to be determined. This part of the EFP-93 project uses transmission of {gamma}-radiation to determine these saturations. In {gamma}-transmission measurements, the electron density of the given substance is measured. This is an advantage as compared to methods that use electric conductivity, since neither oil nor gas conducts electricity. At the moment a single {sup 137}Cs-source is used, but a theoretical investigation of whether it is possible to determine three saturations, using two radioactive sources with different {gamma}-energies, has been performed. Measurements were made on three core plugs. To make sure that the measurements could be reproduced, all the plugs had a point of reference, i.e. a mark so that it was possible to place the plug same way every time. Two computer programs for calculation of saturation and porosity and the experimental setup are listed. (EG).

  10. Plug-In Electric Vehicle Handbook for Consumers (Brochure)

    Energy Technology Data Exchange (ETDEWEB)


    Plug-in electric vehicles (PEVs) are entering the automobile market and are viable alternatives to conventional vehicles. This guide for consumers describes the basics of PEV technology, PEV benefits, how to select the right PEV, charging a PEV, and PEV maintenance.

  11. A Rotating Plug Model of Friction Stir Welding Heat Transfer (United States)

    Raghulapadu J. K.; Peddieson, J.; Buchanan, G. R.; Nunes, A. C.


    A simplified rotating plug model is employed to study the heat transfer phenomena associated with the fiction stir welding process. An approximate analytical solution is obtained based on this idealized model and used both to demonstrate the qualitative influence of process parameters on predictions and to estimate temperatures produced in typical fiction stir welding situations.

  12. Occlusion of pulmonary arteriovenous malformations by use of vascular plug

    DEFF Research Database (Denmark)

    Andersen, P E; Kjeldsen, A D


    Pulmonary arteriovenous malformations are commonly treated by embolization with coils or balloons to prevent cerebral complications and to raise the oxygenation of the blood. The Amplatzer vascular plug is a new occlusive device made of a self-expanding cylindrical nitinol mesh. It is fast and safe...

  13. Evaluation of the TEG® platelet mappingTM assay in blood donors

    DEFF Research Database (Denmark)

    Bochsen, Louise; Wiinberg, Bo; Kjelgaard-Hansen, Mads Jens


    for quantification of platelet function, including the contribution of the adenosine diphosphate (ADP) and thromboxane A2 (TxA2) receptors to clot formation. Methods In 43 healthy blood donors, the analytical (CVa) and inter-individual variability (CVg) of the TEG® Platelet MappingTM assay were determined together...... with platelet receptor inhibition in response to arachidonic acid (AA) and ADP. Results The CVa of the assay for maximal platelet contribution to clot strength (MAThrombin) was 3.5%, for the fibrin contribution to clot strength (MAFibrin) 5.2%, for MAAA 4.5% and for MAADP it was 6.6%. The MAThrombin CVg was 2...

  14. Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover. (United States)

    Stratz, Christian; Nührenberg, Thomas; Amann, Michael; Cederqvist, Marco; Kleiner, Pascal; Valina, Christian M; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald


    Reticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all time-points (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.

  15. A Comparative Study of Apical Healing of Open Apices Using MTA and Ca(OH2 Apical Plugs in Cats

    Directory of Open Access Journals (Sweden)

    M. H. Zarrabi


    Full Text Available Statement of problem: Endodontic treatment of necrotic teeth with open apices is a challenge. After ruling out surgery as a treatment scheme and introduction of the multivisit apexification which in turn had its disadvantages, apical plug seems to be a suitable substitute treatment plan for such cases. Apical plug makes the treatment through formation of a barrier against the obturating material in a single visit.Purpose: The purpose of this study was to compare histologically the periapical healing using MTA and calcium hydroxide apical plugs after intervals of 4 and 12 weeks in cats.Materials and Methods: In this clinical trial study 64 canines of 16 healthy and mature cats were divided into 3 groups after a periapical lesion formation by over instrumentation in the apical area with files up to no.120. The first group included 24 teeth on which MTA apical plug was applied. The second group included 24 teeth on which Ca (OH 2 apical plug was applied. In both groups the canals were filled with gutta percha and sealer. The third group included 16 control teeth whose canals were left empty after instrumentation and debridement. The access cavities of all teeth were sealed with varnish and amalgam and the vital perfusion of cats was performed in 4 and 12 week intervals. Statistical analysis was established by χ2 and independence test.Results: After 4 weeks, periapical healing in the first group was 90%, in the second group 80% and in the third group, it was only 12.5 %. After 12 weeks, periapical healing occurred in 100% of the MTA group, while it was 57.1% in the second and 40%in the third group .Generally, in the study of histological parameters of healing, no statistical significant difference was observed between the 2 experimental groups,although the MTA group results were much better than the Ca (OH 2 group especially at 12 weeks.Conclusion: The use of MTA apical plug is more effective than Ca (OH 2 in treatment of necrotic teeth with open

  16. Hemocompatibility of Polyvinyl Alcohol-Gelatin Core-Shell Electrospun Nanofibers: A Novel Scaffold for Modulating Platelet Deposition and Activation (United States)

    Merkle, Valerie M.; Martin, Daniel; Hutchinson, Marcus; Tran, Phat L.; Behrens, Alana; Hossainy, Samir; Bluestein, Danny; Wu, Xiaoyi; Slepian, Marvin J.


    In this study, we evaluate coaxial electrospun nanofibers with gelatin in the shell and polyvinyl (PVA) in the core as a potential vascular material by determining fiber surface roughness, as well as human platelet deposition and activation under varying conditions. PVA scaffolds had the highest surface roughness (Ra = 65.5 ± 6.8 nm) but the lowest platelet deposition (34.2 ± 5.8 platelets) in comparison to gelatin nanofibers (Ra = 36.8 ± 3.0 nm & 168.9 ± 29.8 platelets) and coaxial nanofibers (1 Gel: 1 PVA coaxial – Ra = 24.0 ± 1.5 nm & 150.2 ± 17.4 platelets; 3 Gel: 1 PVA coaxial – Ra = 37.1 ± 2.8 nm & 167.8 ± 15.4 platelets). Therefore, the chemical structure of the gelatin nanofibers dominated surface roughness in platelet deposition. Due to their increased stiffness, the coaxial nanofibers had the highest platelet activation rate – rate of thrombin formation, in comparison to gelatin and PVA fibers. Our studies indicate that mechanical stiffness is a dominating factor for platelet deposition and activation, followed by biochemical moieties, and lastly surface roughness. Overall, these coaxial nanofibers are an appealing material for vascular applications by supporting cellular growth while minimizing platelet deposition and activation. PMID:25815434

  17. Effects of antiplatelet therapy on platelet extracellular vesicle release and procoagulant activity in health and in cardiovascular disease. (United States)

    Connor, David E; Ly, Ken; Aslam, Anoosha; Boland, John; Low, Joyce; Jarvis, Susan; Muller, David W; Joseph, Joanne E


    Dual antiplatelet therapy with aspirin and clopidogrel is commonly used to prevent recurrent ischemic events in patients with cardiovascular disease. Whilst their effects on platelet reactivity are well documented, it is unclear, however, whether antiplatelet therapy inhibits platelet extracellular vesicle (EV) release. The aim of this study was to investigate the effects of antiplatelet therapy on platelet EV formation and procoagulant activity. Blood samples from 10 healthy controls not receiving antiplatelet therapy were incubated in vitro with aspirin or a P2Y12 inhibitor (MeSAMP). Blood samples from 50 patients receiving long-term dual antiplatelet therapy and undergoing coronary angiography were also studied. Platelet reactivity was assessed by Multiplate™ impedance aggregometry. Platelet EV formation and procoagulant activity of pretreated and untreated blood samples in response to arachidonic acid (AA), adenosine diphosphate (ADP), ADP+PGE1, and thrombin receptor-activating peptide (TRAP) stimulation were assessed by flow cytometry and Procoag-PL assays, respectively. Incubation of normal platelets with aspirin significantly inhibited AA-induced platelet reactivity, EV formation, and procoagulant activity, whilst MeSAMP significantly inhibited platelet reactivity and EV formation in response to AA, ADP, and TRAP, but had minimal effect on procoagulant activity. Most patients receiving dual antiplatelet therapy showed an appropriate reduction in platelet reactivity in response to their treatment; however there was not complete inhibition of increased platelet and EV procoagulant activity in response to ADP, AA, or TRAP. In addition, we could not find any correlation between platelet reactivity and procoagulant activity in patients receiving dual antiplatelet therapy.

  18. Fiscal Year 1993 Well Plugging and Abandonment Program Summary Report Y-12 Plant, Oak Ridge, Tennessee

    Energy Technology Data Exchange (ETDEWEB)



    This report is a synopsis of the progress of the well plugging and abandonment program at the Y-12 Plant, Oak Ridge, Tennessee, from October 1993 through August 1994. A total of 57 wells and borings were plugged and abandoned during the period of time covered in this report. All wells and borings were plugged and abandoned in accordance with the Monitoring Well Plugging and Abandonment Plan for the U.S. Department of Energy, Y-12 Plant, Oak Ridge, Tennessee.

  19. Fiscal year 1993 well plugging and abandonment program, Y-12 Plant, Oak Ridge, Tennessee

    Energy Technology Data Exchange (ETDEWEB)


    This report is a synopsis of the progress of the well plugging and abandonment program at the Y-12 Plant, Oak Ridge, Tennessee, from December 1992 through August 20, 1993. A total of 70 wells and borings were plugged and abandoned during the period of time covered in this report. All wells and borings were plugged and abandoned in accordance with the Monitoring Well Plugging and Abandonment Plan for the US Department of Energy, Y-12 Plant, Oak Ridge, Tennessee (HSW, Inc. 1991).

  20. Initial experience of treating anal fistula with the Surgisis anal fistula plug. (United States)

    Chan, S; McCullough, J; Schizas, A; Vasas, P; Engledow, A; Windsor, A; Williams, A; Cohen, C R


    Complex anal fistulas remain a challenge for the colorectal surgeon. The anal fistula plug has been developed as a simple treatment for fistula-in-ano. We present and evaluate our experience with the Surgisis anal fistula plug from two centres. Data were prospectively collected and analysed from consecutive patients undergoing insertion of a fistula plug between January 2007 and October 2009. Fistula plugs were inserted according to a standard protocol. Data collected included patient demographics, fistula characteristics and postoperative outcome. Forty-four patients underwent insertion of 62 plugs (27 males, mean age 45.6 years), 25 of whom had prior fistula surgery. Mean follow-up was 10.5 months Twenty-two patients (50%) had successful healing following the insertion of plug with an overall success rate of 23 out of 62 plugs inserted (35%). Nineteen out of 29 patients healed following first-time plug placement, whereas repeated plug placement was successful in 3 out of 15 patients (20%; p = 0.0097). There was a statistically significant difference in the healing rate between patients who had one or less operations prior to plug insertion (i.e. simple fistulas) compared with patients who needed multiple operations (18 out of 24 patients vs. 4 out of 20 patients; p = 0.0007). Success of treatment with the Surgisis anal fistula plug relies on the eradication of sepsis prior to plug placement. Plugs inserted into simple tracts have a higher success rate, and recurrent insertion of plugs following previous plug failure is less likely to be successful. We suggest the fistula plug should remain a first-line treatment for primary surgery and simple tracts.

  1. Platelets and infection — an emerging role of platelets in viral infection

    Directory of Open Access Journals (Sweden)

    Alice eAssinger


    Full Text Available Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia and several platelet function disorders increase the risk of bleeding. Over the last years more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients.Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favours platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies.All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count, but also shapes immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation and platelet-mediated modulations of innate and adaptive immune responses.

  2. Platelets and infection - an emerging role of platelets in viral infection. (United States)

    Assinger, Alice


    Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis) are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia) and several platelet function disorders increase the risk of bleeding. Over the last years, more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients. Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favors platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen-antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies. All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count but also shape immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation, and platelet-mediated modulations of innate and adaptive immune responses.

  3. Alternate tube plugging criteria for steam generator tubes

    Energy Technology Data Exchange (ETDEWEB)

    Cueto-Felgueroso, C.; Aparicio, C.B. [Tecnatom, S.A., Madrid (Spain)


    The tubing of the Steam Generators constitutes more than half of the reactor coolant pressure boundary. Specific requirements governing the maintenance of steam generator tubes integrity are set in Plant Technical Specifications and in Section XI of the ASME Boiler and Pressure Vessel Code. The operating experience of Steam Generator tubes of PWR plants has shown the existence of some types of degradatory processes. Every one of these has an specific cause and affects one or more zones of the tubes. In the case of Spanish Power Plants, and depending on the particular Plant considered, they should be mentioned the Primary Water Stress Corrosion Cracking (PWSCC) at the roll transition zone (RTZ), the Outside Diameter Stress Corrosion Cracking (ODSCC) at the Tube Support Plate (TSP) intersections and the fretting with the Anti-Vibration Bars (AVBs) or with the Support Plates in the preheater zone. The In-Service Inspections by Eddy Currents constitutes the standard method for assuring the SG tubes integrity and they permit the monitoring of the defects during the service life of the plant. When the degradation reaches a determined limit, called the plugging limit, the SG tube must be either repaired or retired from service by plugging. Customarily, the plugging limit is related to the depth of the defect. Such depth is typically 40% of the wall thickness of the tube and is applicable to any type of defect in the tube. In its origin, that limit was established for tubes thinned by wastage, which was the predominant degradation in the seventies. The application of this criterion for axial crack-like defects, as, for instance, those due to PWSCC in the roll transition zone, has lead to an excessive and unnecessary number of tubes being plugged. This has lead to the development of defect specific plugging criteria. Examples of the application of such criteria are discussed in the article.

  4. Polysaccharides and bacterial plugging. Final report, 1992--1993

    Energy Technology Data Exchange (ETDEWEB)

    Fogler, H.S.


    In situ core plugging experiments and transport experiments, using the model bacteria Leuconostoc m., have been conducted. Results demonstrated that cellular polysaccharide production increases cell distribution in porous media and caused an overall decrease in media permeability. Further, a parallel core plugging experiment was conducted and showed the feasibility of this system to divert injection fluid from high permeability zones into low permeability zones within porous media as is needed for profile modification. To implement this type of application, however, controlled placement of cells and rates of polymer production are needed. Therefore, kinetic studies were performed. A kinetic model was subsequently developed for Leuconostoc m. bacteria. This model is based on data generated from batch growth experiments and allows for the prediction of saccharide utilization, cell generation, and dextran production. These predictions can be used to develop injection strategies for field implementation. Transport and in situ growth micromodel experiments have shown how dextran allow cells to remain as clusters after cell division which enhanced cell capture and retention in porous media. Additional Damkohler experiments have been performed to determine the effects of the nutrient injection rate and nutrient concentration on the rate of porous media plugging. As shown experimentally and as predicted by a model for in situ growth, an increase in nutrient concentration and/or its injection rate will result in a faster rate of porous media plugging. Through continuum model simulations, it has been shown that the initial cell profiles play a key role on the core plugging rate. Controlling the location of the inoculating cells is thus another key factor in using bacteria for profile modification.

  5. Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo

    DEFF Research Database (Denmark)

    Grüner, Sabine; Prostredna, Miroslava; Schulte, Valerie


    and alphaIIbbeta3. These were identified to be alpha5beta1 and/or alpha6beta1 as alphaIIbbeta3 inhibition abrogated platelet adhesion in beta1-null mice. We conclude that shear-resistant platelet adhesion on the injured vessel wall in vivo is a highly integrated process involving multiple integrin......Damage to the integrity of the vessel wall results in exposure of the subendothelial extracellular matrix (ECM), which triggers integrin-dependent adhesion and aggregation of platelets. The role of platelet beta1 integrins in these processes remains mostly undefined. Here, we demonstrate...... integrin on platelets in wild-type mice blocked aggregate formation and reduced platelet adhesion by 60.0%. Strikingly, alphaIIbbeta3 inhibition had a comparable effect in alpha2-null mice, demonstrating that other receptors mediate shear-resistant adhesion in the absence of functional alpha2beta1...

  6. Ultrastructural changes to rabbit fibrin and platelets due to aspartame. (United States)

    Pretorius, E; Humphries, P


    The coagulation process, including thrombin, fibrin, as well as platelets, plays an important role in hemostasis, contributing to the general well-being of humans. Fibrin formation and platelet activation are delicate processes that are under the control of many small physiological events. Any one of these many processes may be influenced or changed by external factors, including pharmaceutical or nutritional products, e.g., the sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester). It is known that phenylalanine is present at position P(9) and aspartate at position P(10) of the alpha-chain of human fibrinogen, and plays an important role in the conversion of fibrinogen to fibrin by the catalyst alpha-thrombin. The authors investigate the effect of aspartame on platelet and fibrin ultrastructure, by using the rabbit animal model and the scanning electron microscope. Animals were exposed to 34 mg/kg of aspartame 26x during a 2-month period. Aspartame-exposed fibrin networks appeared denser, with a thick matted fine fiber network covering thick major fibers. Also, the platelet aggregates appeared more granular than the globular control platelet aggregates. The authors conclude by suggesting that aspartame usage may interfere with the coagulation process and might cause delayed fibrin breakup after clot formation. They suggest this, as the fibrin networks from aspartame-exposed rabbits are more complex and dense, due to the netlike appearance of the minor, thin fibers. Aspartame usage should possibly be limited by people on anti-clotting medicine or those with prone to clot formation.

  7. Morphological evaluation of canine platelets on Giemsa- and PAS-stained blood smears. (United States)

    Halmay, Dóra; Sótonyi, P; Vajdovich, P; Gaál, T


    The morphology of canine platelets (changes in size, shape, staining characteristics, degree of activation and clump formation, distribution of granules, appearance of vacuoles on Giemsa-stained smears) was investigated in 20 healthy control and 181 diseased dogs. In the group of the sick dogs 84 animals suffered from disorders affecting directly the haematological parameters or the haematopoietic organs such as bleeding, thymic haemorrhage, haemolytic disorders, lymphoma, immune-mediated thrombocytopenia, and other 97 dogs were affected by other diseases (hepatopathy, nephropathy, hepatic, splenic or intestinal neoplasm, skin diseases, diabetes mellitus, Cushing's syndrome, sepsis). The alterations found in platelet morphology were not specific for any disorder. The most common platelet abnormalities were polychromasia and the presence of giant platelets. These changes occurred in a high number in disorders accompanied by bleeding or haemolysis. Anisocytosis was the most frequent finding in hepatic, splenic or intestinal neoplasms and in certain endocrinopathies. Microcytosis was observed in immune-mediated thrombocytopenia, hepatic neoplasms and endocrine disorders. Extreme platelet activation was common in haemolysis, hepatopathies, neoplastic diseases and sepsis. Vacuolisation was present in thymic haemorrhage, pancreatitis, diabetes mellitus and Cushing's syndrome. A new morphologic phenomenon, i.e. a ring-like formation of granules, was described in the cytoplasm of the platelets both in healthy and diseased animals. In addition, two forms of pathologic granulation were also described for the first time in Giemsa-stained blood smears: the pseudonuclear and the spot-like formation of granules, which were observed especially in disorders affecting the blood cells. The granulation and morphological characteristics of platelets on smears stained by periodic acid-Schiff reaction (PAS) were also studied. Three localisations of granulation were observed, such as

  8. 30 CFR 250.1715 - How must I permanently plug a well? (United States)


    ... effective back-pressure control set 50 to 100 feet above the casing shoe, and a cement plug that extends at...-pressure control set 50 to 100 feet above the top of the perforated interval, and a cement plug that.... (7) A subsea well with unsealed annulus A cutter to sever the casing, and you must set a stub plug...

  9. A Case of Randall's Plugs Associated to Calcium Oxalate Dihydrate Calculi

    Directory of Open Access Journals (Sweden)

    Felix Grases


    Full Text Available A case of a patient who developed multiple calcium oxalate dihydrate calculi, some of them connected to intratubular calcifications (Randall's plugs, is presented. Randall's plugs were isolated and studied. The mechanism of Randall's plug development is also suggested.

  10. Test Confessions: A Study of Testing Practices for Plug-in Systems

    NARCIS (Netherlands)

    Greiler, M.; Van Deursen, A.; Storey, M-A.


    Testing plug-in-based systems is challenging due to complex interactions among many different plug-ins, and variations in version and configuration. The objective of this paper is to increase our understanding of what testers and developers think and do when it comes to testing plug-inbased systems.

  11. Strangulated bowel obstruction resulting from mesh plug migration after open inguinal hernioplasty:case report

    Institute of Scientific and Technical Information of China (English)

    LIANG Xiao; CAI Xiu-jun; YU Hong; WANG Yi-fan


    @@ The use of mesh plug in hernioplasty was introduced by Shulman et al 1 in 1990 as a"rolled plug"fixed with two stitches to close the internal inguinal ring.Robbins and Rutkow 2 described their mesh plug technique in 1993.

  12. 40 CFR 144.62 - Cost estimate for plugging and abandonment. (United States)


    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Cost estimate for plugging and... Waste Injection Wells § 144.62 Cost estimate for plugging and abandonment. (a) The owner or operator must prepare a written estimate, in current dollars, of the cost of plugging the injection well...

  13. Methods to Determine the Lagrangian Shear Experienced by Platelets during Thrombus Growth.

    Directory of Open Access Journals (Sweden)

    Isaac P Pinar

    Full Text Available Platelets can become activated in response to changes in flow-induced shear; however, the underlying molecular mechanisms are not clearly understood. Here we present new techniques for experimentally measuring the flow-induced shear rate experienced by platelets prior to adhering to a thrombus. We examined the dynamics of blood flow around experimentally grown thrombus geometries using a novel combination of experimental (ex vivo and numerical (in silico methodologies. Using a microcapillary system, platelet aggregate formation was analysed at elevated shear rates in the presence of coagulation inhibitors, where thrombus formation is predominantly platelet-dependent. These approaches permit the resolution and quantification of thrombus parameters at the scale of individual platelets (2 μm in order to quantify real time thrombus development. Using our new techniques we can correlate the shear rate experienced by platelets with the extent of platelet adhesion and aggregation. The techniques presented offer the unique capacity to determine the flow properties for a temporally evolving thrombus field in real time.

  14. Binding of thrombin-activated platelets to a fibrin scaffold through α(IIbβ₃ evokes phosphatidylserine exposure on their cell surface.

    Directory of Open Access Journals (Sweden)

    Tomasz Brzoska

    Full Text Available Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an α(IIbβ₃ antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.

  15. Evaluation of platelet aggregation in platelet concentrates: storage implications

    Directory of Open Access Journals (Sweden)

    Neiva Teresinha J.C.


    Full Text Available The use of hemo-derivatives is nowadays a fundamentally important therapeutic modality in the exercise of medicine. Among the various hemo-components employed, we have the platelet concentrate (PC, indicated in cases of hemorrhagic disturbances. We previously showed that platelet function in blood donors is reduced in their screening phase and after the separation process of PCs. Currently, we are providing evidence for the existence of biochemical and functional changes in PC preparations stored for three days at temperatures of 20 ± 2 ºC. Platelet concentrates from 40 healthy donors, collected in CPD anticoagulant and PL-146 polyvinylchloride containers, were examined in order to determine the pH value, pCO2 ,pO2 and lactate concentrations. In addition, the aggregation of platelets with thrombin and collagen were examined to evaluate platelet function. A pH increase from 7.07 ± 0.04 to 7.36 ± 0.07 (p < 0.01 was observed. The pCO2 concentration decreased progressively from 69.2 ± 7.7 mmHg to 28.8 ± 6.2 mmHg (p < 0.001 during the storage period. In contrast, pO2 value increase from 103.4 ± 30.6 to 152.3 ± 24.6 mmHg (p < 0.001 was evidenced during the 48 hours of storage. The lactate concentration increased from 17.97 ± 5.2 to 57.21 ± 5.7 mg/dl (p < 0.001. Platelet aggregation using 0.25 U/ml-thrombin and 2.0 µg/ml-collagen showed significant hypofunction from 61.8 ± 2.7% to 24.8 ± 9.8% and 62.7±5.0 to 33.4± 6.2 (p < 0.001, respectively. We concluded that the evaluated biochemical parameters and the platelet function changed significantly when the platelets were kept under routine storage conditions.

  16. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia (United States)

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming


    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  17. An overview of platelet indices and methods for evaluating platelet function in thrombocytopenic patients

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Hvas, Anne-Mette; Nybo, Mads


    in thrombocytopenia. Flow cytometry, platelet aggregometry and platelet secretion tests are used to diagnose specific platelet function defects. The flow cytometric activation marker P-selectin and surface coverage by the Cone and Plate[let] analyser™ predict bleeding in selected thrombocytopenic populations...

  18. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva


    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  19. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva


    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  20. Effect of photodynamic therapy on mouse platelets (United States)

    Zhou, Chuannong; Chi, Shunji; Deng, Jinsheng; Zhang, Hua; Liang, Junlin; Ha, Xian-wen


    Normal mice received hematoporphyrin derivative (HpD) i.v. prior to red light irradiation and the platelet-rich plasma was prepared and irradiated by red light. The platelets were processed for EM examination and stereological analysis. It was shown the 16 hrs after irradiation almost all platelets were necrotized; 8 hours after irradiation about one fourth of the platelets were necrotized and the remaining were considerably damaged. Immediately after irradiation a small number of platelets became necrotic and most other platelets were swollen and deformated, showing significantly increased mean area, perimeter and short axis, and mean cell volume and cell surface area. The findings indicate that platelets are highly sensitive to PDT action and can be directly and rapidly damaged by PDT even in the absence of vascular endothelial cells. The early platelet photoactivation may play an important role in the initiation of early vascular damage and microcirculatory alterations induced by PDT in vivo.

  1. Platelet Disorders: MedlinePlus Health Topic (United States)

    ... Article: Erythropoietin and thrombopoietin mimetics: Natural alternatives to erythrocyte and platelet... Article: Detection of CALR Mutation in Clonal and Nonclonal Hematologic Diseases... Platelet Disorders -- see more articles Thrombocytopenias -- see more ...

  2. Thermo-sensitive polymer nanospheres as a smart plugging agent for shale gas drilling operations. (United States)

    Wang, Wei-Ji; Qiu, Zheng-Song; Zhong, Han-Yi; Huang, Wei-An; Dai, Wen-Hao


    Emulsifier-free poly(methyl methacrylate-styrene) [P(MMA-St)] nanospheres with an average particle size of 100 nm were synthesized in an isopropyl alcohol-water medium by a solvothermal method. Then, through radical graft copolymerization of thermo-sensitive monomer N-isopropylacrylamide (NIPAm) and hydrophilic monomer acrylic acid (AA) onto the surface of P(MMA-St) nanospheres at 80 °C, a series of thermo-sensitive polymer nanospheres, named SD-SEAL with different lower critical solution temperatures (LCST), were prepared by adjusting the mole ratio of NIPAm to AA. The products were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, thermogravimetric analysis, particle size distribution, and specific surface area analysis. The temperature-sensitive behavior was studied by light transmittance tests, while the sealing performance was investigated by pressure transmission tests with Lungmachi Formation shales. The experimental results showed that the synthesized nanoparticles are sensitive to temperature and had apparent LCST values which increased with an increase in hydrophilic monomer AA. When the temperature was higher than its LCST value, SD-SEAL played a dual role of physical plugging and chemical inhibition, slowed down pressure transmission, and reduced shale permeability remarkably. The plugged layer of shale was changed to being hydrophobic, which greatly improved the shale stability.

  3. A high-pressure plug flow reactor for combustion chemistry investigations (United States)

    Lu, Zhewen; Cochet, Julien; Leplat, Nicolas; Yang, Yi; Brear, Michael J.


    A plug flow reactor (PFR) is built for investigating the oxidation chemistry of fuels at up to 50 bar and 1000 K. These conditions include those corresponding to the low temperature combustion (i.e. the autoignition) that commonly occurs in internal combustion engines. Turbulent flow that approximates ideal, plug flow conditions is established in a quartz tube reactor. The reacting mixture is highly diluted by excess air to reduce the reaction rates for kinetic investigations. A novel mixer design is used to achieve fast mixing of the preheated air and fuel vapour at the reactor entrance, reducing the issue of reaction initialization in kinetic modelling. A water-cooled probe moves along the reactor extracting gases for further analysis. Measurement of the sampled gas temperature uses an extended form of a three-thermocouple method that corrects for radiative heat losses from the thermocouples to the enclosed PFR environment. Investigation of the PFR’s operation is first conducted using non-reacting flows, and then with isooctane oxidation at 900 K and 10 bar. Mixing of the non-reacting temperature and species fields is shown to be rapid. The measured fuel consumption and CO formation are then closely reproduced by kinetic modelling using an extensively validated iso-octane mechanism from the literature and the corrected gas temperature. Together, these results demonstrate the PFR’s utility for chemical kinetic investigations.

  4. Effect of platelet age on adhesiveness to collagen and platelet surface charge

    Energy Technology Data Exchange (ETDEWEB)

    Castellan, R.M.; Steiner, M.


    Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (less than or equal to 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.

  5. Dengue platelets meet Sir Arthur Conan Doyle. (United States)

    Bray, Paul F


    In this issue of Blood, Hottz et al provide compelling evidence that dengue virus (DV) induces (1) platelet synthesis of interleukin-1b (IL-1b); (2) platelet-derived IL-1b–containing microvesicles (MVs) that increase vascular permeability; and (3) DV-triggered inflammasome activation in platelets.

  6. Molecular Basis Linking Platelet to Inflammation

    Institute of Scientific and Technical Information of China (English)



    @@ Introduction Blood platelets not only play an important role in hemostasis and thrombosis,but increasing evidence show that they participate in the induction of inflammation.Firstly,platelets contain and release cytokines and immune mediators.And platelets are able to modulate and regulate the function of surrounding cells by adhesion molecules or by the release of various factors.

  7. Platelets Inhibit Migration of Canine Osteosarcoma Cells. (United States)

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C


    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  8. Platelet regulating properties of insulin revisited

    NARCIS (Netherlands)

    Andrade Ferreira, I. (Irlando)


    Disturbances in platelet responsiveness in diabetes mellitus (DM) lead to platelet-dependent complications in the vasculature. Our studies showed that insulin inhibits platelet activation by inhibiting ADP- and thrombin-induced Ca2+ levels. Ca2+ is under control of cAMP that is a potent endogenous p

  9. Image analysis of blood platelets adhesion. (United States)

    Krízová, P; Rysavá, J; Vanícková, M; Cieslar, P; Dyr, J E


    Adhesion of blood platelets is one of the major events in haemostatic and thrombotic processes. We studied adhesion of blood platelets on fibrinogen and fibrin dimer sorbed on solid support material (glass, polystyrene). Adhesion was carried on under static and dynamic conditions and measured as percentage of the surface covered with platelets. Within a range of platelet counts in normal and in thrombocytopenic blood we observed a very significant decrease in platelet adhesion on fibrin dimer with bounded active thrombin with decreasing platelet count. Our results show the imperative use of platelet poor blood preparations as control samples in experiments with thrombocytopenic blood. Experiments carried on adhesive surfaces sorbed on polystyrene showed lower relative inaccuracy than on glass. Markedly different behaviour of platelets adhered on the same adhesive surface, which differed only in support material (glass or polystyrene) suggest that adhesion and mainly spreading of platelets depends on physical quality of the surface. While on polystyrene there were no significant differences between fibrin dimer and fibrinogen, adhesion measured on glass support material markedly differed between fibrin dimer and fibrinogen. We compared two methods of thresholding in image analysis of adhered platelets. Results obtained by image analysis of spreaded platelets showed higher relative inaccuracy than results obtained by image analysis of platelets centres and aggregates.

  10. Plugging of microchannels by spherical particles (United States)

    Climent, Eric; Agbangla, Constant; Bacchin, Patrice


    We investigate by means of numerical simulations the dynamic formation of 3D structures of microparticle aggregates blocking the flow through microchannels. Both the geometries of a straight channel and a sudden reduction of section are analyzed. We use the Force Coupling Method (Climent & Maxey, 2010) to handle simultaneously multi-body hydrodynamic interactions of a confined flowing suspension together with particle/particle and particle/wall surface interactions leading to the adhesion and aggregation of particles. The basic idea of the Force Coupling Method relies on multipole expansion of velocity perturbations induced by the presence of particles in the flow. Simulation results show that varying the magnitude of DLVO interparticle and particle/wall interactions leads to distinct scenarios of pores clogging. We investigate the kinetics of the microchannel occlusion (corresponding to a temporal decrease of the bulk permeability of the channel). We identify the nature of the fouling mechanism: deposition, interception, bridging (see the papers of Sharp & Adrian (2005), Ramachandran & Fogler (1999) and Marshal, 2007).

  11. A critical role for the regulation of Syk from agglutination to aggregation in human platelets. (United States)

    Shih, Chun-Ho; Chiang, Tin-Bin; Wang, Wen-Jeng


    Agglucetin, a tetrameric glycoprotein (GP) Ibα agonist from Formosan Agkistrodon acutus venom, has been characterized as an agglutination inducer in human washed platelets (WPs). In platelet-rich plasma (PRP), agglucetin dramatically elicits a biphasic response of agglutination and subsequent aggregation. For clarifying the intracellular signaling events from agglutination to aggregation in human platelets, we examined the essential signaling molecules involved through the detection of protein tyrosine phosphorylation (PTP). In WPs, an anti-GPIbα monoclonal antibody (mAb) AP1, but not a Src kinase inhibitor PP1, completely inhibited agglucetin-induced agglutination. However, PP1 but not AP1 had a potent suppression on platelet aggregation by a GPVI activator convulxin. The PTP analyses showed agglucetin alone can cause a weak pattern involving sequential phosphorylation of Lyn/Fyn, Syk, SLP-76 and phospholipase Cγ2 (PLCγ2). Furthermore, a Syk-selective kinase inhibitor, piceatannol, significantly suppressed the aggregating response in agglucetin-activated PRP. Analyzed by flow cytometry, the binding capacity of fluorophore-conjugated PAC-1, a mAb recognizing activated integrin αIIbβ3, was shown to increase in agglucetin-stimulated platelets. Again, piceatannol but not PP1 had a concentration-dependent suppression on agglucetin-induced αIIbβ3 exposure. Moreover, the formation of signalosome, including Syk, SLP-76, VAV, adhesion and degranulation promoting adapter protein (ADAP) and PLCγ2, are required for platelet aggregation in agglucetin/fibrinogen-activated platelets. In addition, GPIbα-ligation via agglucetin can substantially promote the interactions between αIIbβ3 and fibrinogen. Therefore, the signal pathway of Lyn/Fyn/Syk/SLP-76/ADAP/VAV/PLCγ2/PKC is sufficient to trigger platelet aggregation in agglucetin/fibrinogen-pretreated platelets. Importantly, Syk may function as a major regulator for the response from GPIbα-initiated agglutination to

  12. Antimicrobial/anti-biofilm activity of expired blood platelets and their released products 

    Directory of Open Access Journals (Sweden)

    Marcin I. Różalski


    Full Text Available Introduction. Although platelets are not part of the classical immune system, they have many features that indicate their role in the anti-infective host defense. They come into interactions with microorganisms, which results in co-aggregation and co-adhesion or destruction of themicrobes due to the action of antimicrobial peptides released from platelets.The aim of this study was to evaluate the killing effect of platelets against planktonic and biofilm cultures of Staphylococcus aureus and to test their synergy with antibiotics. Materials and Methods. S. aureus ATCC 29213; platelet rich plasma (1-3 days post shelf life. Evaluation of bactericidal activity of platelets or their lysates against planktonic cultures of S. aureus – CFU calculation after 4- and 24-hour co-incubation. Assessment of S. aureus biofilm viability under the influence of platelets – Live/Dead® BacLightTM Bacterial Viability Kit. Determination of minimum inhibitory concentrations (MICs (oxacillin, vancomycin, linezolid and estimation of the synergistic action of antibiotics and platelet lysates – a gradient-diffusion test strip. Results. Microbicidal activity of “expired” platelets and their lysates has been shown as a significant reduction in the population of staphylococci in their planktonic cultures by 56-87�0and a decrease in metabolic activity of biofilm formation by 7-38�20These activities were enhanced after activation with ADP. Platelet lysates showed a synergistic effect with β-lactam antibiotic (oxacillin and glycopeptide (vancomycin but not with oxazolidinone (linezolid. Conclusions and Discussion. In summary, platelets even after the medical expiry date are still a good source of antimicrobial low molecular weight proteins (PMPs. Testing of bacterialresistance to PMPs may be advisable as a predictive indicator of susceptibility to treatment of infections such as infective endocarditis and other local infections of biofilm nature.

  13. Human platelet antigen genotyping of platelet donors in southern Brazil. (United States)

    Merzoni, J; Fagundes, I S; Lunardi, L W; Lindenau, J D-R; Gil, B C; Jobim, M; Dias, V G; Merzoni, L; Sekine, L; Onsten, T G H; Jobim, L F


    Human platelet antigens (HPA) are immunogenic structures that result from single nucleotide polymorphisms (SNPs) leading to single amino acid substitutions. This study sought to determine the allele and genotype frequencies of HPA-1, HPA-2, HPA-3, HPA-4, HPA-5 and HPA-15 in platelet donors from the state of Rio Grande do Sul (RS), Brazil, and compare their allele frequencies to those observed in other populations. HPA genotyping was performed by PCR-SSP method. The study sample comprised 201 platelet donors (167 Caucasians and 34 non-Caucasians). Allele 'a' was that most commonly found for HPA-1 to 5 in both groups. The HPA-15ab genotype predominated over homozygous genotypes of this system. Fisher's exact test revealed statistically significant differences for the HPA-5 system, with a greater prevalence of the HPA-5b allele in non-Caucasians. The neighbour-joining method and principal components analysis revealed genetic proximity between our Caucasian group and European populations. We conclude that the allele frequencies of HPA-1 to 5 and HPA-15 found in our Caucasian sample are similar to those reported for European populations. These findings corroborate the ethnic makeup of the population of RS. The higher frequency of the HPA-5b allele found in the non-Caucasian group of our sample suggests the possibility of allosensitization in patients who receive platelet transfusions from genetically incompatible donors.

  14. Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration

    Directory of Open Access Journals (Sweden)

    Ronaldo JFC do Amaral


    Full Text Available Platelet-rich plasma has been used to treat articular cartilage defects, with the expectations of anabolic and anti-inflammatory effects. However, its role on cellular chondrogenic or fibrogenic commitment is still a controversy. Herein, the role of platelet-rich plasma releasate, the product obtained following platelet-rich plasma activation, on cellular commitment toward the chondrogenic lineage was evaluated in vitro. Human nasoseptal chondrogenic cells and human bone marrow mesenchymal stromal cells were used as cell types already committed to the chondrogenic lineage and undifferentiated cells, respectively, as different concentrations of platelet-rich plasma releasate were tested in comparison to commonly used fetal bovine serum. Low concentration of platelet-rich plasma releasate (2.5% presented similar effects on cellular growth compared to 10% fetal bovine serum, for both cell types. In a three-dimensional culture system, platelet-rich plasma releasate alone did not induce full nasoseptal chondrogenic cells cartilage-like pellet formation. Nonetheless, platelet-rich plasma releasate played a significant role on cell commitment as high-passage nasoseptal chondrogenic cells only originated cartilage-like pellets when expanded in the presence of platelet-rich plasma releasate rather than fetal bovine serum. Histological analyses and measurements of pellet area demonstrated that even low concentrations of platelet-rich plasma releasate were enough to prevent nasoseptal chondrogenic cells from losing their chondrogenic potential due to in vitro expansion thereby promoting their recommitment. Low concentration of platelet-rich plasma releasate supplemented in chondrogenic medium also increased the chondrogenic potential of mesenchymal stromal cells seeded on collagen-hyaluronic acid scaffolds, as observed by an increase in chondrogenic-related gene expression, sulfated glycosaminoglycan production, and compressive modulus following in vitro

  15. Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration (United States)

    Matsiko, Amos; Tomazette, Marcel RP; Rocha, Wanessa KR; Cordeiro-Spinetti, Eric; Levingstone, Tanya J; Farina, Marcos; O’Brien, Fergal J; El-Cheikh, Marcia C; Balduino, Alex


    Platelet-rich plasma has been used to treat articular cartilage defects, with the expectations of anabolic and anti-inflammatory effects. However, its role on cellular chondrogenic or fibrogenic commitment is still a controversy. Herein, the role of platelet-rich plasma releasate, the product obtained following platelet-rich plasma activation, on cellular commitment toward the chondrogenic lineage was evaluated in vitro. Human nasoseptal chondrogenic cells and human bone marrow mesenchymal stromal cells were used as cell types already committed to the chondrogenic lineage and undifferentiated cells, respectively, as different concentrations of platelet-rich plasma releasate were tested in comparison to commonly used fetal bovine serum. Low concentration of platelet-rich plasma releasate (2.5%) presented similar effects on cellular growth compared to 10% fetal bovine serum, for both cell types. In a three-dimensional culture system, platelet-rich plasma releasate alone did not induce full nasoseptal chondrogenic cells cartilage-like pellet formation. Nonetheless, platelet-rich plasma releasate played a significant role on cell commitment as high-passage nasoseptal chondrogenic cells only originated cartilage-like pellets when expanded in the presence of platelet-rich plasma releasate rather than fetal bovine serum. Histological analyses and measurements of pellet area demonstrated that even low concentrations of platelet-rich plasma releasate were enough to prevent nasoseptal chondrogenic cells from losing their chondrogenic potential due to in vitro expansion thereby promoting their recommitment. Low concentration of platelet-rich plasma releasate supplemented in chondrogenic medium also increased the chondrogenic potential of mesenchymal stromal cells seeded on collagen-hyaluronic acid scaffolds, as observed by an increase in chondrogenic-related gene expression, sulfated glycosaminoglycan production, and compressive modulus following in vitro culture. On the

  16. Platelet count and platelet indices in women with preeclampsia

    Directory of Open Access Journals (Sweden)

    AlSheeha MA


    Full Text Available Muneera A AlSheeha,1 Rafi S Alaboudi,1 Mohammad A Alghasham,1 Javed Iqbal,2 Ishag Adam1 1Department of Obstetrics and Gynaecology, College of Medicine, Qassim University, Buriadah, 2Department of Obstetrics and Gynecology, Maternity and Children’s Hospital, Qassim, Kingdom of Saudi Arabia Background: Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia.Objective: To compare platelet indices, namely platelet count (PC, mean platelet volume (MPV, platelet distribution width (PDW, and PC to MPV ratio in women with preeclampsia compared with healthy controls.Setting: Qassim Hospital, Kingdom of Saudi Arabia.Design: A case–control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls.Results: There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC curves, the PC cutoff was 248.0×103/µL for diagnosis of preeclampsia (P=0.019; the area under the ROC curve was 62.4%. Binary regression suggests that women with PC <248.010×103/µL were at higher risk of preeclampsia (odds ratio =2.2, 95% confidence interval =1.08–4.6, P=0.03. The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia (P=0.035, the area under the ROC curve was 62.2%.Conclusion: PC <248.010×103/µL and PC to MPV ratio 31.2 are valid predictors of preeclampsia. Keywords: preeclampsia, platelets, PDW, mean platelet

  17. [Platelet-rich plasma (platelet gel) in secondary alveoloplasty in cleft patients]. (United States)

    Méndez, R; López-Cedrún, J L; Patiño, B; Vázquez, I; Martín-Sastre, R; Tellado, M G; Vela, D


    The use of Platelet-rich plasma (platelet gel--PRP--) was introduced in the oral and maxilofacial surgery 10 years ago. Its good results are due to the quickly generation of new bone and the acceleration of the period of surgical scar formation. Its employment in the alveolar reconstruction of the cleft patient is not still consistent and the works published in the literature are infrequent. The objective of this preliminary study is presenting our experience with the use of PRP in the reconstruction of the alveolar congenital defects of cleft patients. Between July 2002 and January 2004 were operated 14 patients with congenital alveolar cleft carrying out an standard secondary alveoloplasty. In 12 cases was employed cancellous bone of iliac crest and in two cases the donor area was tibial. The laboratory of Hematology of our Hospital prepared the plasma gel rich in platelets by means of a double centrifuge of autologous serum of the patient. After adding calcium a rich gel in platelets in approximate quantities of 1-2 ml was obtained. In this preliminary report we have studied the aspect of the surgical injury the 3er postoperative day, and the first and second weeks after intervention. These results were compared carried out previously with the Standard alveoloplasty without use of the PRP. Likewise we evaluated the bony density by means of intraoral Rx at 3 and 6 months postoperative. The injury of the alveoloplasty healed more quickly in the patients in which plasma enriched gel was employed. The patients referred less pain and edema in the first days of the postoperative period. The alveolar bony regeneration was faster to the 3 months, though the result was similar in the intraoral Rx to the 6 months. The necessary quantities of cancellous bone were smaller in all cases in which the plasma enriched gel was used (30% less). The use of Platelet-rich plasma (PRP) is a valid protocol for the reconstruction in patients with congenital alveolar clefts. Its low

  18. Processing of nanolitre liquid plugs for microfluidic cell-based assays

    Directory of Open Access Journals (Sweden)

    Junji Fukuda, Shintaro Takahashi, Tatsuya Osaki, Naoto Mochizuki and Hiroaki Suzuki


    Full Text Available Plugs, i.e. droplets formed in a microchannel, may revolutionize microfluidic cell-based assays. This study describes a microdevice that handles nanolitre-scale liquid plugs for the preparation of various culture setups and subsequent cellular assays. An important feature of this mode of liquid operation is that the recirculation flow generated inside the plug promotes the rapid mixing of different solutions after plugs are merged, and it keeps cell suspensions homogeneous. Thus, serial dilutions of reagents and cell suspensions with different cell densities and cell types were rapidly performed using nanolitres of solution. Cells seeded through the plug processing grew well in the microdevice, and subsequent plug processing was used to detect the glucose consumption of cells and cellular responses to anticancer agents. The plug-based microdevice may provide a useful platform for cell-based assay systems in various fields, including fundamental cell biology and drug screening applications.

  19. Inhibitory effects of yuzu and its components on human platelet aggregation. (United States)

    Kim, Tae-Ho; Kim, Hye-Min; Park, Se Won; Jung, Yi-Sook


    Our previous study demonstrated that yuzu has an anti-platelet effect in rat blood. In the present study, we examined whether the anti-platelet effect of yuzu can be extended to human blood by investigating its ability to inhibit aggregations induced by various agonists in human platelet rich plasma (PRP). This study also investigated the underlying mechanism of yuzu focusing on ADP granule secretion, TXB2 formations, and PLCγ/Akt signaling. The results from this study showed that ethanolic yuzu extract (YE), and its components, hesperidin and naringin, inhibited human platelet aggregation in a concentration-dependent manner. YE, hesperidin and naringin also inhibited TXB2 formation and ADP release. The phosphorylation of PLCγ and Akt was significantly inhibited by YE, heperidin and naringin. Furthermore, we demonstrated that YE, heperidin and naringin has anti-platelet effects in rat ex vivo studies, and lower side effects in mice tail bleeding time studies. The results from this study suggest that YE, hesperidin and naringin can inhibit human platelet aggregation, at least partly through the inhibition of PLCγ and Akt, leading to a decrease in TXB2 formation and granule secretion.

  20. Platelet count and platelet indices in women with preeclampsia. (United States)

    AlSheeha, Muneera A; Alaboudi, Rafi S; Alghasham, Mohammad A; Iqbal, Javed; Adam, Ishag


    Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia. To compare platelet indices, namely platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and PC to MPV ratio in women with preeclampsia compared with healthy controls. Qassim Hospital, Kingdom of Saudi Arabia. A case-control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls. There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC) curves, the PC cutoff was 248.0×10(3)/µL for diagnosis of pre-eclampsia (P=0.019; the area under the ROC curve was 62.4%). Binary regression suggests that women with PC preeclampsia (odds ratio =2.2, 95% confidence interval =1.08-4.6, P=0.03). The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia (P=0.035, the area under the ROC curve was 62.2%). PC preeclampsia.

  1. Pooled platelet concentrates: an alternative to single donor apheresis platelets? (United States)

    Pietersz, R N I


    Three types of platelet concentrates (PC) are compared: PC either processed with the platelet-rich plasma (PRP) or the Buffy coat (BC) method from whole blood units and PC obtained by apheresis. Leuko-reduction (LR) pre-storage is advocated to improve quality of the PC during storage and reduce adverse reactions in recipients. Standardization of methods allow preparation of PC with comparable yields of approximately 400 x 10(9) platelets in pooled non-LR-PRP, approximately 370 x 10(9) in pooled LR-BC-PC and in LR apheresis PC the number of platelets can be targeted on 350 x 10(9) or more with devices of various manufacturers. While viral transmission can be prevented by outstanding laboratory tests, the risk of bacterial contamination should be reduced by improved arm disinfection, deviation of the first 20-30 ml of blood and culture or rapid detection assays of the PC pre-issue. In a large prospective multicenter trial no significant difference was observed between cultures of apheresis PC (n = 15,198): 0.09% confirmed positive units versus 0.06% in pooled BC-PC (n = 37,045), respectively. Though platelet activation as measured by CD62 expression may differ in vitro in PC obtained with various apheresis equipment, and also between PC processed with the two whole blood methods there is scarce literature about the clinical impact of these findings. In conclusion the final products of LR-PC derived from whole blood or obtained by apheresis can be comparable, provided the critical steps of the processing method are identified and covered and the process is in control.

  2. Polymer grouts for plugging lost circulation in geothermal wells.

    Energy Technology Data Exchange (ETDEWEB)

    Galbreath, D. (Green Mountain International, Waynesvile, NC); Mansure, Arthur James; Bauer, Stephen J.


    We have concluded a laboratory study to evaluate the survival potential of polymeric materials used for lost circulation plugs in geothermal wells. We learned early in the study that these materials were susceptible to hydrolysis. Through a systematic program in which many potential chemical combinations were evaluated, polymers were developed which tolerated hydrolysis for eight weeks at 500 F. The polymers also met material, handling, cost, and emplacement criteria. This screening process identified the most promising materials. A benefit of this work is that the components of the polymers developed can be mixed at the surface and pumped downhole through a single hose. Further strength testing is required to determine precisely the maximum temperature at which extrusion through fractures or voids causes failure of the lost circulation plug.

  3. Plug and Process Loads Capacity and Power Requirements Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sheppy, M.; Gentile-Polese, L.


    This report addresses gaps in actionable knowledge that would help reduce the plug load capacities designed into buildings. Prospective building occupants and real estate brokers lack accurate references for plug and process load (PPL) capacity requirements, so they often request 5-10 W/ft2 in their lease agreements. Limited initial data, however, suggest that actual PPL densities in leased buildings are substantially lower. Overestimating PPL capacity leads designers to oversize electrical infrastructure and cooling systems. Better guidance will enable improved sizing and design of these systems, decrease upfront capital costs, and allow systems to operate more energy efficiently. The main focus of this report is to provide industry with reliable, objective third-party guidance to address the information gap in typical PPL densities for commercial building tenants. This could drive changes in negotiations about PPL energy demands.

  4. Strength and stability of microbial plugs in porous media

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, A.K. [NIPER/BDM-Oklahoma, Inc., Bartlesville, OK (United States); Sharma, M.M.; Georgiou, G. [Univ. of Texas, Austin, TX (United States)


    Mobility reduction induced by the growth and metabolism of bacteria in high-permeability layers of heterogeneous reservoirs is an economically attractive technique to improve sweep efficiency. This paper describes an experimental study conducted in sandpacks using an injected bacterium to investigate the strength and stability of microbial plugs in porous media. Successful convective transport of bacteria is important for achieving sufficient initial bacteria distribution. The chemotactic and diffusive fluxes are probably not significant even under static conditions. Mobility reduction depends upon the initial cell concentrations and increase in cell mass. For single or multiple static or dynamic growth techniques, permeability reduction was approximately 70% of the original permeability. The stability of these microbial plugs to increases in pressure gradient and changes in cell physiology in a nutrient-depleted environment needs to be improved.

  5. Migrated Mesh Plug Masquerading as a Bladder Tumor (United States)

    Dajani, Daoud; Aron, Monish


    Abstract Background: The purpose of this case presentation is to demonstrate how erosion of mesh into the bladder can initially present with the same symptoms as bladder malignancy. Case Presentation: A 62-year-old Hispanic male presented with 2 years of hematuria along with imaging concerning for a bladder tumor. The patient underwent cystoscopy with biopsy of a lesion at the anterior bladder. It was ultimately determined that a mesh plug from a prior hernia repair had migrated into the bladder. The mesh plug was excised using the Da Vinci Si robot, which allowed for efficient mobilization of the bladder and other anatomic structures, as well as rapid recovery. Conclusion: Our case demonstrates the need to consider mesh erosion as a cause of hematuria and, furthermore, shows how the robotic approach can help facilitate excision of migrated mesh into the bladder. PMID:28164159

  6. Flow induced vibration studies on PFBR control plug components

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, V., E-mail: [Fast Reactor Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamilnadu (India); Kumar, P. Anup; Anandaraj, M.; Thirumalai, M.; Anandbabu, C.; Rajan, K.K. [Fast Reactor Technology Group, Indira Gandhi Centre for Atomic Research, Kalpakkam, Tamilnadu (India)


    Highlights: Black-Right-Pointing-Pointer Flow induced vibration studies on Prototype Fast Breeder Reactor control plug model carried out. Black-Right-Pointing-Pointer Velocity similitude was followed for the study. Black-Right-Pointing-Pointer Frequencies and amplitude of vibrations of various control plug components measured. Black-Right-Pointing-Pointer Overall values of vibration are well within permissible limits. - Abstract: The construction of Prototype Fast Breeder Reactor (PFBR), a 500 MWe liquid sodium cooled reactor, is in progress at Kalpakkam in India. Control plug (CP) is located right above the core subassemblies in the hot pool. Control plug is an important component as many of the critical reactor parameters are sensed and controlled by the components housed in the control plug assembly. In PFBR primary circuit, components are basically thin walled, slender shells with diameter to thickness ratio ranging from 100 to 650. These components are prone to flow induced vibrations. The existence of free liquid (sodium) surfaces, which is the source of sloshing phenomenon and the operation of primary sodium pump in the primary pool are other potential sources of vibration of reactor components. Control plug is a hollow cylindrical shell structure and provides passages and support for 12 absorber rod drive mechanisms (ARDM) which consists of 9 control and safety rods and 3 diverse safety rods, 210 thermo wells to measure the sodium temperature at the exit of various fuel subassemblies, three failed fuel localization modules (FFLM) and acoustic detectors. It consists of a core cover plate (CCP), which forms the bottom end, two intermediate supports plate, i.e. lower stay plate (LSP) and upper stay plate (USP) and an outer shell. The CCP is located at a distance of 1.3 m from the core top. With such a gap, there will be long free hanging length of the thermocouple sleeves, Delayed neutron detector (DND) sampling tubes and ARDM shroud tubes and hence they are

  7. Effect of ionizing radiation on platelet function in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kalovidouris, A.E.; Papayannis, A.G. (Evangelismos Hospital, Athens (Greece))


    The effect of ionizing radiation on platelet function was investigated in vitro. Platelet-rich plasma (300x10/sup 9//l) was irradiated with doses of 1, 4, 10, 20 and 50 Gy. Platelet function tests were performed on both irradiated and control (non-irradiated) platelet samples. The platelet function tests were (1) platelet aggregation by ADP (1, 2, 4 final concentration), adrenaline and collagen, (2) ADP-release from platelets, (3) clot retraction and (4) platelet factor-3 availability. It was found that roentgen irradiation of platelets in vitro did not affect these platelet function tests.

  8. A Rigorous Methodology for Analyzing and Designing Plug-Ins

    DEFF Research Database (Denmark)

    Fasie, Marieta V.; Haxthausen, Anne Elisabeth; Kiniry, Joseph


    . This paper addresses these problems by describing a rigorous methodology for analyzing and designing plug-ins. The methodology is grounded in the Extended Business Object Notation (EBON) and covers informal analysis and design of features, GUI, actions, and scenarios, formal architecture design, including...... behavioral semantics, and validation. The methodology is illustrated via a case study whose focus is an Eclipse environment for the RAISE formal method's tool suite....

  9. Maturity Assessment of Space Plug-and-Play Architecture (United States)


    EPC ) to convert the standard bus voltage to the necessary component voltages. In light of these voltage requirements, SPA introduced a the developers to decide how to implement those functions. Assessing software maturity for contractor -developed software will be difficult at...Comtech AA) and Seakr are two of the Advanced Plug-and-Play Technology (APT) contractors . Comtech AA demonstrated a full system utilizing SPA

  10. Plug-In Electric Vehicle Handbook for Workplace Charging Hosts

    Energy Technology Data Exchange (ETDEWEB)



    Plug-in electric vehicles (PEVs) have immense potential for increasing the country's energy, economic, and environmental security, and they will play a key role in the future of U.S. transportation. By providing PEV charging at the workplace, employers are perfectly positioned to contribute to and benefit from the electrification of transportation. This handbook answers basic questions about PEVs and charging equipment, helps employers assess whether to offer workplace charging for employees, and outlines important steps for implementation.

  11. Experimental Investigation of Near-Borehole Crack Plugging with Bentonite (United States)

    Upadhyay, R. A.; Islam, M. N.; Bunger, A.


    The success of the disposal of nuclear waste in a deep borehole (DBH) is determined by the integrity of the components of the borehole plug. Bentonite clay has been proposed as a key plugging material, and its effectiveness depends upon its penetration into near-borehole cracks associated with the drilling process. Here we present research aimed at understanding and maximizing the ability of clay materials to plug near-borehole cracks. A device was constructed such that the borehole is represented by a cylindrical chamber, and a near-borehole crack is represented by a slot adjacent to the center chamber. The experiments consist of placing bentonite clay pellets into the center chamber and filling the entire cavity with distilled water so that the pellets hydrate and swell, intruding into the slot because the cell prohibits swelling in the vertical direction along the borehole. Results indicate that the bentonite clay pellets do not fully plug the slot. We propose a model where the penetration is limited by (1) the free swelling potential intrinsic to the system comprised of the bentonite pellets and the hydrating fluid and (2) resisting shear force along the walls of the slot. Narrow slots have a smaller volume for the clay to fill than wider slots, but wider slots present less resistive force to clay intrusion. These two limiting factors work against each other, leading to a non-monotonic relationship between slot width and intrusion length. Further experimental results indicate that the free swelling potential of bentonite clay pellets depends on pellet diameter, "container" geometry, and solution salinity. Smaller diameter pellets possess more relative volumetric expansion than larger diameter pellets. The relative expansion of the clay also appears to decrease with the container size, which we understand to be due to the increased resistive force provided by the container walls. Increasing the salinity of the solution leads to a dramatic decrease in the clay

  12. National Plug-In Electric Vehicle Infrastructure Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Eric W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Rames, Clement L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Muratori, Matteo [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Srinivasa Raghavan, Seshadri [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Melaina, Marc W [National Renewable Energy Laboratory (NREL), Golden, CO (United States)


    This document describes a study conducted by the National Renewable Energy Laboratory quantifying the charging station infrastructure required to serve the growing U.S. fleet of plug-in electric vehicles (PEVs). PEV sales, which include plug-in hybrid electric vehicles (PHEVs) and battery electric vehicles (BEVs), have surged recently. Most PEV charging occurs at home, but widespread PEV adoption will require the development of a national network of non-residential charging stations. Installation of these stations strategically would maximize the economic viability of early stations while enabling efficient network growth as the PEV market matures. This document describes what effective co-evolution of the PEV fleet and charging infrastructure might look like under a range of scenarios. To develop the roadmap, NREL analyzed PEV charging requirements along interstate corridors and within urban and rural communities. The results suggest that a few hundred corridor fast-charging stations could enable long-distance BEV travel between U.S. cities. Compared to interstate corridors, urban and rural communities are expected to have significantly larger charging infrastructure requirements. About 8,000 fast-charging stations would be required to provide a minimum level of coverage nationwide. In an expanding PEV market, the total number of non-residential charging outlets or 'plugs' required to meet demand ranges from around 100,000 to more than 1.2 million. Understanding what drives this large range in capacity requirements is critical. For example, whether consumers prefer long-range or short-range PEVs has a larger effect on plug requirements than does the total number of PEVs on the road. The relative success of PHEVs versus BEVs also has a major impact, as does the number of PHEVs that charge away from home. This study shows how important it is to understand consumer preferences and driving behaviors when planning charging networks.

  13. Mesh Plug Repair of Inguinal Hernia; Single Surgeon Experience

    Directory of Open Access Journals (Sweden)

    Ahmet Serdar Karaca


    Full Text Available Aim: Mesh repair of inguinal hernia repairs are shown to be an effective and reliable method. In this study, a single surgeon%u2019s experience with plug-mesh method performs inguinal hernia repair have been reported. Material and Method: 587 patients with plug-mesh repair of inguinal hernia, preoperative age, body / mass index, comorbid disease were recorded in terms of form. All of the patients during the preoperative and postoperative hernia classification of information, duration of operation, antibiotics, perioperative complications, and later, the early and late postoperative complications, infection, recurrence rates and return to normal daily activity, verbal pain scales in terms of time and postoperative pain were evaluated. Added to this form of long-term pain ones. The presence of wound infection was assessed by the presence of purulent discharge from the incision. Visual analog scale pain status of the patients was measured. Results: 587 patients underwent repair of primary inguinal hernia mesh plug. One of the patients, 439 (74% of them have adapted follow-ups. Patients%u2019 ages ranged from 18-86. Was calculated as the mean of 47±18:07. Follow-up period of the patients was found to be a minimum of 3 months, maximum 55 months. Found an average of 28.2±13.4 months. Mean duration of surgery was 35.07±4.00 min (min:22mn-max:52mn, respectively. When complication rates of patients with recurrence in 2 patients (0.5%, hematoma development (1.4% in 6 patients, the development of infection in 11 patients (2.5% and long-term groin pain in 4 patients (0.9% appeared. Discussion: In our experience, the plug-mesh repair of primary inguinal hernia repair safe, effective low recurrence and complication rates can be used.



    P.Thiyagarajan; G.Aghila; V. Prasanna Venkatesan


    In spite of existence of many standard security mechanisms for ensuring secure e- Commerce business, users still fall prey for onlin e attacks. One such simple but powerful attack is ‘Phishing’. Phishing is the most alarming threat in the e-Commerce world and effective anti-phishing technique is the need of the hour. This paper focuses on a novel anti-phishing browser plug-in which uses information hiding technique - Steganography. A Robust Message based Im...

  15. Pixastic: Steganography based Anti-Phihsing Browser Plug-in


    P.Thiyagarajan; G.Aghila; Venkatesan, V. Prasanna


    In spite of existence of many standard security mechanisms for ensuring secure e-Commerce business, users still fall prey for online attacks. One such simple but powerful attack is 'Phishing'. Phishing is the most alarming threat in the e-Commerce world and effective anti-phishing technique is the need of the hour. This paper focuses on a novel anti-phishing browser plug-in which uses information hiding technique - Steganography. A Robust Message based Image Steganography (RMIS) algorithm has...

  16. Nuclear analysis of ITER Test Blanket Module Port Plug

    Energy Technology Data Exchange (ETDEWEB)

    Villari, Rosaria, E-mail: [ENEA, Fusion Technical Unit, Nuclear Technologies Laboratory, Via Enrico Fermi 45, 00044 Frascati, Rome (Italy); Kim, Byoung Yoon; Barabash, Vladimir; Giancarli, Luciano; Levesy, Bruno; Loughlin, Michael; Merola, Mario [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 Saint Paul-lez-Durance Cedex (France); Moro, Fabio [ENEA, Fusion Technical Unit, Nuclear Technologies Laboratory, Via Enrico Fermi 45, 00044 Frascati, Rome (Italy); Pascal, Romain [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 Saint Paul-lez-Durance Cedex (France); Petrizzi, Luigino [European Commission, DG Research & Innovation G5, CDMA 00/030, B-1049 Brussels (Belgium); Polunovsky, Eduard; Van Der Laan, Jaap G. [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 Saint Paul-lez-Durance Cedex (France)


    Highlights: • 3D nuclear analysis of the ITER TBM Port Plug (PP). • Calculations of neutron fluxes, nuclear heating, damage and He-production in TBM PP components. • Shutdown dose rate assessment with Advanced D1S method considering different configurations. • Potential design improvements to reduce the shutdown dose rate in the port interspace. - Abstract: Nuclear analyses have been performed for the ITER Test Blanket Module Port Plug (TBM PP) using the MCNP-5 Monte Carlo Code. A detailed 3D model of the TBM Port Plug with dummy TBM has been integrated into the ITER MCNP model (B-lite v.3). Neutron fluxes, nuclear heating, helium production and neutron damage have been calculated in all the TBM PP components. Global shutdown dose rate calculations have also been performed with Advanced D1S method for different configurations of the TBM PP system. This paper presents the results of these analyses and discusses potential design improvements aiming to further reduce the shutdown dose rate in the port interspace.

  17. Selecting a Control Strategy for Plug and Process Loads

    Energy Technology Data Exchange (ETDEWEB)

    Lobato, C.; Sheppy, M.; Brackney, L.; Pless, S.; Torcellini, P.


    Plug and Process Loads (PPLs) are building loads that are not related to general lighting, heating, ventilation, cooling, and water heating, and typically do not provide comfort to the building occupants. PPLs in commercial buildings account for almost 5% of U.S. primary energy consumption. On an individual building level, they account for approximately 25% of the total electrical load in a minimally code-compliant commercial building, and can exceed 50% in an ultra-high efficiency building such as the National Renewable Energy Laboratory's (NREL) Research Support Facility (RSF) (Lobato et al. 2010). Minimizing these loads is a primary challenge in the design and operation of an energy-efficient building. A complex array of technologies that measure and manage PPLs has emerged in the marketplace. Some fall short of manufacturer performance claims, however. NREL has been actively engaged in developing an evaluation and selection process for PPLs control, and is using this process to evaluate a range of technologies for active PPLs management that will cap RSF plug loads. Using a control strategy to match plug load use to users' required job functions is a huge untapped potential for energy savings.

  18. Plug and Play Integration through Space Object Standardization (United States)

    Boyce, Leslye; Meyers, Gary; Rigsbee, Emmett; Branch, William; Shaw, Jeffrey; Poole, David


    Plug and play is an industry standard promoted by Intel and Microsoft, and others that allows users to add and remove various input and output devices without making specific customizations to their systems. The idea behind concept is that using standard products eases integration of components and promotes capabilities of conforming products. The concept works because vendors comply with a standard specification. This paper reports the development of a reference architecture for the mission control domain, which is leveraging off this revolutionary concept. Standards are being developed at the application layer, which enable "plug and play" of mission software products. A Mission Control, reference architecture has been defined. For each sub-domain, the interfaces are modeled in Interface Definition Language (IDL). A subset of the IDL has been developed within both commercial off-the-shelf (COTS) and government (GOTS) products. Selected vendors have agreed to modify their products to be compatible with the defined IDL. The plug and play integration of these different products has been validated in a demonstration testbed.

  19. Platelets: crossroads of immunity and hemostasis. (United States)

    Jenne, Craig N


    In this issue of Blood, Koupenova and colleagues report that platelets express functional TOLL-like receptor 7 (TLR7) and contribute to host survival during viral infection. Through a series of experiments utilizing mice deficient for TLR7 together with adoptive transfer of wild-type platelets, Koupenova et al demonstrate that platelets specifically respond to viral analogs and intact virus, leading to platelet activation and binding to various leukocyte subsets. Perhaps most importantly, this platelet activation appears absolutely essential for host survival during infection with some viral pathogens such as encephalomyocarditis virus (EMCV).

  20. Evidence that platelet buoyant density, but not size, correlates with platelet age in man. (United States)

    Mezzano, D; Hwang, K; Catalano, P; Aster, R H


    Following infusion of 51Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radio-activity of LD platelets declined rapidly post-infusion (T1/2 = 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3--4-day period and gradually declined for 6--7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P less than 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33) days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P less than 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets = 7.57 mu3, LD platelets = 6.87 mu3, 0.05 less than P less than 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.

  1. Evidence that platelet buoyant density, but not size, correlates with platelet age in man

    Energy Technology Data Exchange (ETDEWEB)

    Mezzano, D.; Hwang, K.; Catalano, P.; Aster, R.H.


    Following infusion of 51Cr-labeled autologous platelets into normal subjects, high-density (HD) and low-density (LD) platelet cohorts were isolated by prolonged centrifugation in isosmotic arabino-galactan (Stractan). Specific radio-activity of LD platelets declined rapidly post-infusion (T1/2 . 1.5 days), but specific radioactivity of HD platelets remained constant or increased over a 3--4-day period and gradually declined for 6--7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high-density albumin were labeled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (P less than 0.02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33) days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (P less than 0.05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets . 7.57 mu3, LD platelets . 6.87 mu3, 0.05 less than P less than 0.01). We believe the most logical interpretation of these findings is that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, specific radioactivity of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled cells; specific radioactivity of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions.

  2. Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation. (United States)

    Boilard, Eric;