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1
MacMillan, L. J. M. "Receptor mechanisms common to platelets and platelet progenitor cells." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233116.
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Box, Clare Louise. "Interactions between platelets and platelet derived microvesicles in inflamation." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5818/.
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Atherosclerosis is a chronic inflammatory disease, characterised by infiltration of leukocytes and accumulation of fatty deposits in the artery wall. Early events in this disease process include recruitment of platelets to the artery wall, which in turn aid in leukocyte recruitment. However, upon activation platelets release microvesicles (PMV), we are interested in whether PMV have a role in enhancing leukocyte recruitment. We demonstrated using whole blood that upon activation, platelets form aggregates with monocytes and neutrophils. The data suggests that upon platelet activation, PMV may be generated and subsequently may have a role in heterotypic aggregate formation observed. Interestingly, lymphocytes did not form aggregates with platelets (or PMV) as readily. We showed that blocking P-selectin leads to a significant reduction in heterotypic aggregate formation. We also demonstrated the presence of P-selectin glycoprotein ligand-1 (PSGL 1), the ligand with the highest binding affinity for P-selectin, on monocytes and neutrophils. Monocytes preferentially bound platelets or PMV. However, we found no significant increase in recruitment of these heterotypic aggregates to von Willebrand factor, under conditions of low shear stress compared to monocytes alone. These heterotypic aggregates provide a mechanism for cross-talk between cell types and have a potential role in inflammatory and thrombotic diseases.
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Taha, Mariam. "Bacterial Contamination of Platelet Concentrates: Role of Biofilm Formation and Manufacturing Process." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35192.
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Bacterial contamination of platelet concentrates (PCs) poses the highest transfusion-associated infectious risk with skin flora, such as Staphylococcus epidermidis and Staphylococcus capitis, being the predominant contaminants. These bacteria are able to form surface-attached aggregates or biofilms, which are present in the skin of healthy blood donors and can subsequently be isolated from contaminated PCs.
Disinfection of the venipuncture area before donation with a combination of 2% chlorhexidine-gluconate and 70% isopropanol is used at Canadian Blood Services. However, not all bacteria are eliminated during skin disinfection since contaminated PCs are still captured during routine PC screening. In this thesis, the ability of biofilm-forming S. epidermidis and S. capitis to resist the currently used disinfectants was explored. It was demonstrated that although a combination of chlorhexidine and isopropanol has a bactericidal effect, it is unable to completely eradicate skin flora biofilms.
Several countries have implemented Pathogen Inactivation Technologies (PITs) as a measure to help control transfusing bacterially-contaminated PCs by exposing PC units to ultra violet light. However, no investigations have been done to evaluate the ability of PITs against bacterial biofilms, which was one of the objectives of this thesis. Data revealed that the efficacy of a currently used PIT, the Mirasol® system, is similar for S. epidermidis present in PCs produced from whole blood inoculated with biofilm or non-biofilm cells. However, treatment effectiveness was strain dependent. In conclusion, further investigation to improve donor skin disinfection and PITs should be considered.
Surveillance at Canadian Blood Services shows that contamination rates in single-donor apheresis PCs (Aph-PCs) is generally higher than in four-donor buffy coat platelet pools (BC-PCs). This study investigated whether the BC-PC production method contributes to this observation as BC-PCs are derived from WB that is left to rest overnight while Aph-PCs are collected directly from the donor. Data showed that WB hold during BC-PC production does not have a broad-spectrum bactericidal effect and therefore other factors contribute to low rates of contamination in BC-PCs. The work presented in this thesis provides an insight to bacterial residence and persistence during blood product manufacturing and makes suggestions for PC safety improvements.
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Hayman, Melissa Anne. "Genomic influences on platelet function." Thesis, Queen Mary, University of London, 2018. http://qmro.qmul.ac.uk/xmlui/handle/123456789/36221.
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The study of platelet messenger and micro-RNAs is of increasing interest owing to the fact that platelets contain the machinery to splice and translate mRNA into proteins in response to inhibitory or activating signals. However, the relatively small size (roughly 4000-5000 transcripts) and short half-life of the platelet transcriptome makes this a technically challenging aspect of platelet biology to investigate. The aims of these thesis investigations were therefore to optimise protocols for the isolation of platelets for downstream RNA analyses and function testing, to investigate the functional capabilities of platelet subpopulations rich in RNA, and to understand the functional and transcriptomic impact of gene mutations predicted to influence platelet function. I found that the optimal method for isolating platelets from whole blood is to use simple single step centrifugation to obtain platelet rich plasma. This method is as effective as more involved methods at reducing white blood cell contamination whilst causing minimal platelet activation. Using this method in combination with flow cytometric cell sorting techniques I was able to isolate the newly formed reticulated platelet sub-population and to confirm the link between reticulation status and increased RNA content. Furthermore, using a range of platelet function assays I demonstrated that reticulated platelets are more reactive than non-reticulated platelets. By obtaining blood samples from a patient with a PLA2G4A mutation I was able to show that loss of cPLA2α enzymatic activity alters both platelet function and the expression of certain mRNA transcripts. My investigations using samples from a range of patients with bleeding tendencies show the benefit of combining deep platelet phenotyping with next generation sequencing to understand the causation of bleeding disorders. Together these investigations highlight the utility of genomic DNA and platelet specific mRNA studies in providing novel insights in to pathways regulating platelet reactivity.
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Hamali, Hassan A. A. "Regulation of the procoagulant activity of platelets and platelet-derived microparticles." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/10046.
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Procoagulant microparticles (MPs) in the circulation are increasingly recognized as playing a role in haemostasis and inflammation and may prove useful biomarkers for clinical studies. Platelets are known to generate MPs in response to stimulation, and platelet-derived MPs (PDMPs) form the majority of the MPs found in the normal circulation and can be elevated in a number of disease states. The current study has focused on the procoagulant activity of platelets and PDMPs following stimulation with the collagen-mimetic peptide CRP-XL. Their activity in accelerating thrombin generation can be accurately measured by the Calibrated Automated Thrombogram (CAT) assay using 1pM TF reagent to initiate the reaction, with the finding that plasma from patients with chronic renal disease has significant thrombin generation due to increased procoagulant activity of MPs. Conversely premature MI patients in a stable condition have thrombin generation comparable to matched healthy control. In all subjects, removal of MPs from plasma by filtration (>0.2 μm) eliminates this procoagulant activity, indicating the importance of MP size in driving the procoagulant response. The procoagulant activity of activated platelets and PDMPs showed a strong correlation with annexin-V binding measured using flow cytometry. Comparison of the regulatory mechanism of the procoagulant activity of platelet and PDMPs upon activation with platelets undergoing apoptosis showed that although both activation and apoptosis resulted in exposure of the procoagulant surface, apoptotic platelets did not release procoagulant MPs or show any markers of activation such as P-selectin expression, fibrinogen binding or aggregation. Reactive oxygen species (ROS) are generated during platelet activation or apoptosis mainly through the NADP(P)H oxidase pathway. The procoagulant activity of platelets and PDMPs was significantly attenuated (as measured by thrombin generation and annexin-V binding) by inhibition of the NAD(P)H oxidase pathway by apocynin, which had similar inhibition on other platelet responses including on 12-HETE generation, TxB2 production and aggregation. However antioxidants only inhibited apoptosis-induced platelet procoagulant activity. These data demonstrate significant involvement of ROS in platelet procoagulant activity induced by both activation and apoptosis and suggest the involvement of lipid peroxidation during apoptosis.
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Murphy, Christine Therese. "Mechanisms of stimulus-response coupling in platelet-activating factor stimulated platelets." Thesis, University of Bath, 1992. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304999.
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Arunima, Ghosh. "Role of CD36 in Platelet Function." Cleveland State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=csu1199991110.
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Hamad, Osama A. "Crosstalk Between Activated Platelets and the Complement System." Doctoral thesis, Uppsala universitet, Enheten för klinisk immunologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-123681.
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Several studies have shown that complement and thrombotic events co-exist. Platelets have been suspected to act as the bridge between the two cascade systems. To study the platelet-induced complement activation we developed a system in which platelets were activated by thrombin receptor activating peptide (TRAP) in platelet rich plasma (PRP) or whole blood anti-coagulated using the specific thrombin inhibitor, lepirudin. TRAP-activated platelets induced a fluid-phase complement activation measured as generation of C3a and sC5b-9, triggered by released chondroitin sulphate-A (CS-A) which interacted with C1q and activated the complement system through the classical pathway. Complement components C1q, C3, C4 and C9 were also shown to bind to TRAP-activated platelets but this binding did not seem to be due to a complement activation since blocking of complement activation at the C1q or C3 levels did not affect the binding of the complement proteins. The C3 which bound to activated platelets consisted of C3(H2O), indicating that bound C3 was not proteolytically activated. Binding of C1q was partially dependent on CS-A exposure on activated platelets. The abolished complement activation on the surface of activated platelets was suggested to be dependent on the involvement of several complement inhibitors. We confirmed the binding of C1INH and factor H to activated platelets. To this list we have added another potent complement inhibitor, C4BP. The binding of factor H and C4BP was shown to be dependent on exposure of CS-A on activated platelets. The physiological relevance of these reactions was reflected in an elevated expression of CD11b on leukocytes, and increased generation of platelet-leukocyte complexes. The platelets were involved in these events by at least two different mechanisms; generation of C5a which activated leukocytes and binding of C3(H2O)/iC3(H2O), a ligand to the intergrin CD11b/CD18 on their surface. These mechanisms add further to the understanding of how platelets interact with the complement system and will help us to understand the role of the complement system in cardiovascular disease and thrombotic conditions.Platelet Mediated Complement Activation
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Battram, Anthony Matthew. "The role and regulation of Rasa3 in platelets and platelet cell models." Thesis, University of Bristol, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702741.
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Upon vascular insult, platelets are recruited to the site of injury, are activated, and form a haemostatic plug to prevent bleeding. However, inappropriate platelet activation can lead to the formation of occluding thrombi in arteries and veins in a process known as thrombosis. The GTPase Rap1 plays a critical role in platelet activation by regulating the affinity state of the fibrinogen receptor, integrin allbb3. The aim of this thesis was to ascertain the role and regulation of a Rap1-targeting GTPase-activating protein (GAP), Rasa3 (previously GAP1lP4BP), in platelet signal transduction and function. I first investigated possible mechanisms of Rasa3 regulation in platelets, and I found that platelet Rasa3 bound to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3), suggesting a role of PI3 kinase. Although PI(3,4,5)P3 binding had no direct effect on Rasa3 Rap1 GAP activity in vitro, Pl3 kinase did regulate Rasa3 subcellular localisation and activation of Rasa3 substrate, Rap1. Rasa3 also underwent thrombin-induced phosphorylation and associated with integrin b3. Next, to assess potential effects of Rasa3 on platelet function, I used a CHO cell model of integrin allbb3 signalling, C19 cells. I demonstrated that Rasa3 Rap1GAP activity was responsible for inhibiting integrin allbb3-mediated C19 cell spreading. I then characterised two Rasa3 mutants, H794L and G125V, found in thrombocytopaenic mouse models. I found that both mutations caused a loss of Rasa3 Rap1GAP and RasGAP activity, and Rasa3 inhibition of C19 cell spreading. Furthermore, platelets from mice expressing Rasa3 (H794L) exhibit increased spreading in a manner that is insensitive to PI3 kinase inhibition, suggesting that Pl3 kinase regulates platelet spreading by blocking Rasa3 Rap1GAP activity. I finally evaluated CMK cells as a possible cell line in which to study the effect of Rasa3 on platelet signalling and integrin allbb3 activation, and I found that they have some advantages compared to the C19 cell model. Overall, this thesis establishes a novel role for Rasa3 in platelet integrin allbb3 outside-in signalling and begins to explore the Pl3 kinase-dependent and -independent mechanisms of Rasa3 regulation.
10
Eriksson, Andreas. "Platelet Adhesion to Proteins in Microplates : Applications in Experimental and Clinical Research." Doctoral thesis, Linköping : Department of Medical and Health Sciences, Linköping University, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-11733.
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Cicmil, Milenko. "Platelet endothelial cell adhesion in molecule -1 (PECAM-1/CD31) signalling in platelets." Thesis, University of Reading, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270922.
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Edwards, Rebecca Susan. "Synthesis of graphene platelets." Thesis, Durham University, 2015. http://etheses.dur.ac.uk/11132/.
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Graphene, a single-layer of graphite, is frequently termed a ‘wonder material’ due to the wide range of extraordinary properties it possesses and the potential it has for uses in a broad variety of different applications. Key to the realisation of graphene’s use in applications is the ability to produce large scale quantities of graphene with consistent quality, which remains a challenge to the field. The aim of this thesis was to investigate the synthesis of graphene via a number of different methodologies in order to develop novel techniques that are suitable to scale and that provide graphene materials that are useful in different applications. To this aim, four studies were carried out; two involving the ‘top-down’ synthesis of graphene from graphite and two involving the ‘bottom-up’ synthesis of graphene from molecular precursors. In the first study a series of intermediate materials between graphene oxide (GO) and reduced GO (rGO) were successfully produced using a well-controlled reduction reaction, and the trend in their properties was explored, while in the second study rGO was successfully produced using a novel method that is simple, scalable and environmentally friendly. In both these studies a novel method of handling GO was used that eliminated the requirement for the final, time consuming purification step of GO synthesis. In the third study bulk graphene platelets were successfully produced using a novel chemical vapour deposition (CVD) method, and in the final study the templated growth of graphene via CVD over metal microcrystals was investigated. The work builds on some relatively new concepts for graphene synthesis; including tailoring the graphene product to the particular application and size/shape control for bulk scale graphene platelets, and also presents an interesting case study on carbon growth on copper which may provide new insights into carbon synthesis in these systems.
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Joutsi-Korhonen, Lotta. "Autoimmune thrombocytopenia : detection of platelet-associated IgG, reticulated platelets and platelet Fcg[gamma] receptor polymorphism in thrombocytopenic patients." Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/joutsi-korhonen/.
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Bunescu, Andreia. "Cellular markers indicating activation of the hemostatic system : studies on platelets and leukocytes in peripheral human blood /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-759-2/.
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Tohidi-Esfahani, Ibrahim. "Molecular profiling and characterisation of the procoagulant platelet subpopulation." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/29642.
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Platelets play a major role in thrombotic disorders, with current antiplatelet agents limited by bleeding complications. The procoagulant platelet, implicated in thrombosis, has little role in haemostasis and specifically targeting it could improve thrombotic outcomes. This work aimed to develop a method to isolate procoagulant platelets, interrogate the transcriptome to identify key biological pathways for the formation of the subpopulation, and evaluate the pathways in downstream experiments.
RNA-sequencing of healthy donor platelets identified >1000 genes differentially expressed between procoagulant and activated/non-procoagulant platelets from the same donor, confirming the molecularly distinct nature of the procoagulant platelet. Enriched biological pathways included actin cytoskeleton, endocytosis, calcium signalling and leukocyte interaction pathways, among others.
Three identified pathways were explored. The role of dynamin, involved in actin and endocytosis pathways, was assessed. Dynamin inhibitor MiTMAB reduced procoagulant platelets generated by thrombin and glycoprotein-VI stimulation from 30.5±3.0% to 2.9±0.3% (p<0.001), while platelet activation was preserved (>99% P-selectin+). The novel discovery of dynamin as a key player in procoagulant platelet formation may have a future clinical role. STIM1, which mediates cellular calcium entry, was also assessed, with inhibition preventing procoagulant platelet formation. Elevated procoagulant platelets could also be used to identify STIM1 gain-of-function mutations. Testing the importance of leukocyte interaction, platelet concentrates for transfusion had blunted agonist-induced procoagulant platelet formation which normalised upon return into whole blood.
This work, through deep molecular profiling, has generated a large amount of previously unavailable data for hypothesis generation and advancements in the field. This may facilitate discovery of novel anti-thrombotic therapeutics and diagnostics.
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VISMARA, MAURO. "Blood platelets and cancer: the involvement of platelet-derived extracellular vesicles in tumour progression." Doctoral thesis, Università degli studi di Pavia, 2021. http://hdl.handle.net/11571/1425254.
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In addition to their roles in haemostasis and thrombosis, blood platelets have been extensively implicated in the progression of cancer. During metastasis, circulating tumour cells (CTCs) induce platelet activation and aggregation, that are exploited to increase cancer dissemination though multiple mechanisms [1, 2].
Platelet-derived extracellular vesicles (PEVs) are shed from platelet membrane in response to extracellular stimuli and carry important biological signals to recipient cells. In vitro, cancer cells induce the release of PEVs and, accordingly, cancer patients display increased levels of circulating PEVs [3, 4]. PEVs are known mediators of cell-to-cell communication and gaining growing attention as potential mediators of the platelet-cancer interplay [5]. Nevertheless, PEVs ability to regulate target cancer cells is largely unexplored.
This study aims to investigate the effects of PEVs on breast cancer cells in vitro. Four breast cancer cell lines MDA-MB-231, SKBR3, MCF-7, and BT474, characterized by different metastatic potential, were used. PEVs were purified by differential centrifugation from thrombin-stimulated platelets. Breast cancer cells were co-cultured with PEVs and different aspects were analysed.
PEVs specifically bind to different breast cancer cells and elicit cell-specific functional responses.
We found that PEVs massively interact with the metastatic cell lines MDA-MB-231 and SKBR3 and the ductal carcinoma cell line BT474, but not with MCF-7 cell line. Confocal microscopy analysis demonstrated that PEVs are internalized by the three cell lines, although with different efficiency. PEVs internalization was associated to the acquisition of the specific platelet marker integrin αIIb, as demonstrated by several approaches, such as immunofluorescence microscopy and immunoblotting analyses.
Within 48 hours, in SKBR3 and BT474 cell lines, PEVs induced minor alteration in the different phases of the cell cycle without affecting cell viability. Conversely, PEVs potently stimulated migration and invasion of MDA-MB-231, without affecting the progression of cell cycle.
PEVs triggered a sustained increase of intracellular Ca2+ concentration in MDA-MB-231, SKBR3 and BT474 cells, indicating that these microvesicles activate signalling responses that may influence the behaviour of recipient cells. Although in all the analysed breast cancer cells PEVs evoked intracellular Ca2+ mobilization, only in MDA-MB-231 cells the event was associated to the stimulation of selected signalling proteins implicated in migration, including p38MAPK and myosin light chain 2 (MLC2). Importantly, the inhibition of myosin light chain phosphorylation by a Rho kinase inhibitor prevented PEVs-stimulated migration of MDA-MB-231 cells.
Our results indicate that different breast cancer cells can interact and internalize PEVs, which induce intercellular calcium movements. Moreover, PEVs are versatile regulators of cancer cell behaviour and elicit a variety of different responses depending on the specific breast cancer cell subtype.
References
1. Gay, L.J. and B. Felding-Habermann, Contribution of platelets to tumour metastasis. Nat Rev Cancer, 2011. 11(2): p. 123-34.
2. Bambace, N.M., J.E. Levis, and C.E. Holmes, The effect of P2Y-mediated platelet activation on the release of VEGF and endostatin from platelets. Platelets, 2010. 21(2): p. 85-93.
3. Zarà, M., et al., Release of Prometastatic Platelet-Derived Microparticles Induced by Breast Cancer Cells: A Novel Positive Feedback Mechanism for Metastasis. TH Open, 2017. 1(2): p. e155-e163.
4. Chaari, M., et al., Impact of breast cancer stage, time from diagnosis and chemotherapy on plasma and cellular biomarkers of hypercoagulability. BMC Cancer, 2014. 14: p. 991.
5. Mezouar, S., et al., Involvement of platelet-derived microparticles in tumor progression and thrombosis. Semin Oncol, 2014. 41(3): p. 346-58.
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Ledent-Semple, Elisabeth. "A study of factors influencing the quality of blood products during preparation, storage and filtration /." Linköping : Univ, 2001. http://www.bibl.liu.se/liupubl/disp/disp2001/med667s.pdf.
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McGrath, Brianna. "A mechanobiological investigation of platelets." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28299.
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To investigate the mechanical behavior of platelets in response to an applied force, the deformation capacity of the membrane, as quantified by membrane progression into a borosilicate glass micropipette of defined internal diameter, is probed using a controlled range of negative pressure (0--7 cm H2O). In real-time, murine platelet membranes fail to demonstrate viscoelastic effects, but maintain an average linear deformation behavior (n = 11 platelets). Along with published deformation data using human platelets, a novel constitutive model generates a set of optimized material constants that accurately predict platelet membrane behavior. Using MATLAB (Version 7.4), the model is able to preserve platelet deformation at constant volume by implementing the Levenberg-Marquardt method, and ultimately generates an experimentally validated simulation program of micropipette aspiration. Finally, as a complement to these products, the tension and stretch responses to a specific magnitude of negative pressure are resolved.
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Law, Robert. "PDE3A signalling in blood platelets." Thesis, University of Hull, 2016. http://hydra.hull.ac.uk/resources/hull:13761.
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Cyclic 3’, 5’ adenosine monophosphate (cAMP) signalling downstream of prostacyclin (PGI₂) is a key inhibitory pathway in blood platelets. This pathway is dynamically regulated by phosphodiesterase 3A (PDE3A), which hydrolyses cAMP into metabolically inactive AMP. Although PDE3A is an established drug target in anti-platelet therapies, the molecular mechanisms that underlie its function in platelets remain unclear. Therefore, the major aim of this study was to further explore PDE3A signalling in human platelets. Using a combination of cell fractionation and immunoblotting we identified two PDE3A splice variants in platelets, PDE3A1 and PDE3A2, that were differentially localised within the cell. PDE3A1 was located in the membrane fraction, whereas PDE3A2 was primarily located in the cytosolic fraction. Treatment of platelets with PGI2 induced a transient phosphorylation of PDE3A2 at Ser³¹² in a PKA dependent manner. In contrast, no phosphorylation of PDE3A1 was detected. The phosphorylation of PDE3A2 was associated with increased PDE3A enzymatic activity, which suggested that cAMP signalling activated only the cytosolic form of the enzyme. In many cells, A-kinase anchoring proteins (AKAPs) orchestrate a coordinated response between PKA and its effector proteins. The phosphorylation and activation of PDE3A2 in response to PGI2 was blunted by a cell permeable peptide inhibitor of PKA-AKAP interactions suggesting that PKA-mediated activation of PDE3A2 was dependent on an AKAP. Using a cAMP-pull down approach to enrich cAMP binding proteins combined with immunoblotting, we confirmed the presence of two AKAP7 isoforms (δ and γ) in platelets. Additionally, we found that AKAP7δ co-precipitated with PDE3A2 and possessed associated PDE3A activity. Furthermore, AKAP7 also possessed PKA activity, which was a result of its constitutive association with PKA-II. Critically, immunoprecipitated PDE3A was found to be co-associated with both PKA-II and AKAP7δ. The findings in this thesis suggest that blood platelets express multiple differentially-regulated PDE3A splice variants, of which PDE3A2 is regulated by PKA-II within a novel cytosolic AKAP7δ facilitated signalling complex. The selective inhibition of PDE3A splice variants and/or pharmacological disruption of PDE3A signalosomes may provide safer and more specific ways of controlling pathological platelet activation.
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MacKenzie, Amanda Barbara. "Ion channels in human platelets." Thesis, University of Cambridge, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.627035.
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Stott, Andrew James. "Studies on human blood platelets." Thesis, University of Warwick, 1990. http://wrap.warwick.ac.uk/57766/.
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This project was undertaken to increase the understanding of platelet function, with paticular emphasis on abnormal platelets in diabetes mellitus, and improving the quality of platelet concentrates for transfusion. {1} Potential platelet antagonists, including PGE1, verapamil, insulin and hirudin, were added to platelet concentrates in an attempt to improve the recovery and shelf-life of the concentrate. Each "preservative" caused some improvement in platelet concentrate quality, as measured by functional tests, and radio-immunoassay for the platelet activation marker, B- thromboglobulin. The best results were obtained with the addition of PGE1, which facilitated recovery of all samples to which it was added, suggesting a cheap way of ensuring consistently good platelet concentrates. {2} Various investigations were carried out regarding abnormal platelet function in diabetes mellitus. No significant differences were found in the responses of platelets from diabetics and age-matched controls to the calcium-channel blocking drug, Verapamil, in vitro. Similarly, the capacity of diabetic platelets to produce malondialdehyde, a by-product of thromboxane A2 synthesis, was not significantly different from control platelets. The use of insulin in aggregometry studies showed, surprisingly, that insulin could have a pro-aggregatory effect on platelets from diabetics, but not those from healthy controls. In addition, evidence for the existence of a platelet aggregation-enhancing factor in the plasma of diabetics and older controls was obtained. {3} Extensive tests to investigate the nature of spontaneous platelet aggregation (SPA) in whole blood have established the existence of two types of SPA, (i) ADP-dependent, and (ii) ADP-independent. The results obtained suggest a major role for erythrocytes in the development of inappropriate platelet aggregation.
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Tatsis, A. "Hydraulic conveying of metallic platelets." Thesis, Imperial College London, 1987. http://hdl.handle.net/10044/1/46749.
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Chang, Karin. "Platelets and Serotonin in Migraine." University of Toledo Health Science Campus / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1279586929.
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Kremer, Hovinga Johanna Anna. "Malondialdehyd fomation by blood platelets /." Bern, 1990. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Hille, Laura [Verfasser], and Dietmar [Akademischer Betreuer] Trenk. "Intrinsic properties of reticulated platelets." Freiburg : Universität, 2020. http://d-nb.info/122441652X/34.
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Bhavaraju, Kamala. "MOLECULAR PHYSIOLOGY OF THROMBOXANE A2 GENERATION IN PLATELETS." Diss., Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/92746.
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Molecular and Cellular PhysiologyPh.D.
Cardiovascular diseases are a major cause of mortality and morbidity in the developed countries. Anti-platelet therapy is a cornerstone treatment for patients with cardiovascular diseases. Patients are routinely managed with a combination therapy consisting of aspirin and clopidogrel. Aspirin inhibits cyclooxygenase 1 (COX 1) a crucial intermediate enzyme involved in thromboxane biosynthesis. Clopidogrel on the other hand antagonizes ADP receptor P2Y12. ADP is a weak platelet agonist stored in platelet dense granules and is released upon platelet activation. ADP activates platelets through two purinergic receptors namely P2Y1 and P2Y12 these receptors couple to Gq and Gi class of G-proteins, respectively. P2Y1 causes calcium mobilization through activation of PLC-β. P2Y12 inhibits adenylyl cyclase, causes activation of Rap1B and Akt. Signaling from both the receptors is required for complete integrin activation, thromboxane generation and Erk activation. Previous studies have shown that P2Y12 potentiates fibrinogen receptor activation, secretion, thrombi stabilization, thrombin generation, platelet leukocyte aggregation formation. ThromboxaneA2 (TXA2) is a potent platelet agonist generated through arachidonic acid metabolism in platelets. TXA2 thus, generated after platelet activation acts as a positive feedback mediator along with ADP. Under physiological conditions, platelet activation leads to thrombin generation through coagulation cascades. Generated thrombin activates PAR receptors and ADP is released from dense granules, which further potentiates thromboxane generation downstream of PARs. Current anti-platelet therapy regimens often include P2Y12 antagonists and aspirin in management of patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI) with stent implantation. However, there still exists a need for improved treatment strategies as not all patients benefit from this dual combination therapy. Reasons include, poor responders either to P2Y12 antagonists or to aspirin, or if aspirin is contraindicated in these patient populations. In the current study we evaluated the role of P2Y12 in thromboxane generation under physiological conditions. We studied serum thromboxane generation in a model system wherein P2Y12 was antagonized or deficient. Using pharmacological approaches we show that dosing mice with 30mg/Kg/body weight clopidogrel or 3mg/Kg/body weight prasugrel decreased serum thromboxane levels when compared to the control mice. Pre-treatment of human blood ex vivo with active metabolites of clopidogrel (R361015) or prasugrel (R138727) also led to reduction in thromboxane levels. We also evaluated serum thromboxane levels in P2Y receptor null mice, serum thromboxane levels in P2Y1 null mice were similar to those in wild type littermates, and were inhibited in P2Y12 null mice. Furthermore, serum thromboxane levels in P2Y12 deficient patients, previously described in France and Japan, were also evaluated and these patients had lower serum thromboxane levels compared to normal controls. In a pilot study, serum thromboxane levels were radically reduced in healthy human volunteers upon dosing with clopidogrel, compared to the levels before dosing. In conclusion, P2Y12 antagonism alone can decrease physiological thromboxane levels. Thus P2Y12 regulates physiological thromboxane levels. Further it is known that ADP-induced thromboxane generation is integrin-dependent. However it is not clear if other potent platelet agonists like thrombin require outside-in signaling for thromboxane generation. Our results show that thrombin-induced thromboxane generation was independent of integrins i.e. when platelets were stimulated with PAR agonists in presence of fibrinogen receptor antagonist thromboxane generation was not affected. Since PAR agonists, unlike ADP, activate G12/13 signaling pathways. Hence, we hypothesized that these pathways might play a role in TXA2 generation. Our results show, that inhibition of ADP-induced thromboxane generation by fibrinogen receptor antagonist SC57101 was rescued by costimulation of G12/13 pathways with YFLLRNP. This observation suggested an existence of a common signaling effector downstream of integrins and G12/13 pathways. Next, we evaluated role of three potential tyrosine kinases; c-Src, Syk and FAK (Focal Adhesion Kinase) that are known to be activated by integrins. Our results showed that c-Src and Syk kinase did not play a role in ADP-induced functional responses in platelets. We observed differential activation of FAK downstream of integrins and G12/13 pathways. ADP-induced activation of FAK was integrindependent and SFK-independent. On the other hand selective activation of G12/13 pathway lead to FAK activation, in SFK and Rho dependent manner. We also evaluated specificity of new FAK inhibitor TAE-226 to understand the role of FAK in TXA2 generation. Our results showed that TAE-226 exhibited non-specific effects at higher concentrations. Furthermore, in comparison to WT mice, FAK null mice did not show any difference in TXA2 generation. Therefore, we concluded that differential activation of FAK occurs downstream of Integrins and G12/13 pathways. However, the common effector molecule downstream of integrins and G12/ 13 pathways contributing to TXA2 generation in platelets remains elusive.
Temple University--Theses
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Milovanovic, Micha. "Platelets : with special reference to platelet density subpopulations, stable coronary heart disease and atrial fibrillation." Doctoral thesis, Linköpings universitet, Hälsa, Aktivitet, Vård (HAV), 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-62630.
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The current thesis was divided into two parts. Basic platelet research is the topic of the first section. The subsequent clinical part examines platelet reactivity in stable angina pectoris (AP) and in atrial fibrillation. Platelet heterogeneity was investigated in the first section (papers 1 and 2). The cells were separated according to density using linear Percoll™ (a density medium) gradients. The latter contained EDTA, prostaglandin E1 and theophylline to prevent platelet in vitro activity. The platelet population was then divided into density subpopulations (n = 16 - 20). Membrane attached fibrinogen was determined with a flow cytometer technique and used as a marker reflecting platelet in vivo activity. Platelet P-Selectin content was employed to estimate the quantity of platelet α-granules. Paper I examined healthy blood donors (n = 3). The second report (paper II) compared healthy volunteers (n = 2) and subjects with essential thrombocythemia (ET) (n = 2). The latter is a clonal disease being characterized by an excessive platelet production. Platelet counts were determined in all fractions. In manuscripts I and II determination of surface bound fibrinogen and intracellular P-Selectin was carried out in 12 and 16 platelet density fractions, respectively. High density platelets displayed more surface bound fibrinogen indicating in vivo activity. They also contained less P-Selectin. The latter finding implies platelet in vivo release reactions. Low density platelets circulated with more surface bound fibrinogen as well. Compared with peak density platelets, lighter cells contained more P-Selectin. ET was characterized by a similar platelet density pattern in that high and low density platelets displayed more surface bound fibrinogen. The similarity may explain why severe bleedings do not occur more frequently in ET. It is also obvious from the current thesis that the significance of platelet heterogeneity remains unclear and stimulates to further research. In particular, future work must involve more patients. The second part (papers III-VI) of the thesis was devoted to stable AP and atrial fibrillation. Determination of platelet reactivity i.e. platelet bound fibrinogen after stimulation was carried out in whole blood. A flow cytometer technique was employed (papers III-VI). Adenosine diphosphate (ADP) (1.7 and 8.5 μmol/L) and a thrombin-receptor activating peptide (TRAP-6) (57 and 74 μmol/L) were used as stimulating agents. Determination of peak platelet density (kg/L) was utilized as a further measure reflecting platelet reactivity (paper V). Surface bound and soluble P-Selectin were employed as platelet activity markers (paper VI). Gender differences with respect to platelet reactivity were investigated in paper III. Paper IV examined platelets in stable AP without significant coronary flow obstruction(s) as determined by coronary angiography. In a following study platelet reactivity was analysed in diabetes type II complicated by stable AP (paper V). Finally, long-term (more than 2 years) outcome of atrial fibrillation was related to platelet reactivity and activity (paper VI). In this study the subjects were investigated at the initial electrical cardioversion and the analysis were repeated after more than 2 years. Postmenopausal women with stable AP demonstrated more reactive platelets when stimulating with TRAP-6. They had higher platelet counts (paper III) as well. Stable AP without significant coronary flow obstruction(s) was associated with elevated platelet reactivity (paper IV). Diabetes type II was linked to higher peak platelet density and elevated platelet reactivity (paper V). Augmented platelet reactivity proved to be a feature of subjects remaining in atrial fibrillation more than 2 years after the electrical cardioversion (paper VI). In contrast, the irregular heart rhythm did not affect platelet activity. It is to assume that platelets at least partly are responsible for the sometimes atypical symptoms of females with stable AP. It is also conceivable to speculate that platelets contribute to chest pain in AP free from significant coronary flow obstruction(s). Theoretically, enhanced platelet reactivity could at least partly explain why diabetes type II affects the prognosis of coronary heart disease. The thesis further shows a possible theoretical link between atrial fibrillation, increased platelet reactivity and clot formation.
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Forsyth, Sara. "The effect of exercise on the concentration of platelets in a platelet rich plasma preparation." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/40420.
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Traumatic tendon injuries and tendinopathy are common problems in sports medicine practice. The active population seeks minimally invasive treatments that speed healing time. New strategies, such as platelet-rich plasma (PRP) therapies, may achieve this. The use of PRP in sports medicine has been stimulated by the advancing knowledge regarding the role of growth factors (GF) in tissue repair. GF concentration is thought to increase linearly with platelet concentration (Eppley et al., 2004). Several studies are emerging with favourable outcomes in injection of PRP into the area of injury (Kon et al., 2009, Mishra & Pavelko, 2006). Some postulate that the greater the concentration of platelets in a sample the greater the healing augmentation (Smith, 2009). There is a lack of literature addressing the clinically practical issue of how to best maximize the platelet-enhanced product drawn from the patient. The purpose of this study was to evaluate the effect of 2 exercise intensities on the concentration of platelets in a PRP preparation. The participants exercised on a cycle ergometer on three occasions. First, a V0₂max test was carried out. The participant then exercised, on two separate days, for 15 minutes at 50% (moderate exercise) or at 85% (intense exercise) of their predetermined V0₂max heart rate. Blood was drawn at baseline and within 3 minutes post exercise. The samples were prepared into a PRP preparation. The concentration of platelets was analyzed in the PRP. We found a significant increase in the concentration of platelets in the post-intense exercise PRP samples. No significant increase was seen in the moderate exercise condition. A significant effect was found for the mean differences between pre and post in the moderate versus intense exercise groups. These results indicate that intense exercise is a practical and safe way to increase the concentration of platelets in a PRP sample.
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Sink, Carolyn A. "Canine Platelet Concentrates: An In Vitro Study to Effectively Provide a Source of Functional Platelets." Thesis, Virginia Tech, 2002. http://hdl.handle.net/10919/31620.
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This study monitored the storage lesion of 15 units of canine platelet concentrates harvested by differential centrifugation. Canine platelet concentrates were stored at 20-24° C in a platelet rotator for a total of 9 days; the storage lesion of three second generation platelet storage containers was compared. The battery of in vitro tests used to monitor the storage lesion were selected from previous studies performed with human platelet concentrates separated by differential centrifugation. Based on these tests, canine platelet concentrates exhibited a storage lesion similar to human platelet concentrates. Metabolic analytes demonstrated decreasing pH, carbon dioxide, bicarbonate and glucose concentrations concurrent with increasing oxygen and lactate dehydrogenase activity over the 9-day period. Platelet structural changes were monitored by mean platelet volume, which began to increase on Day-5. Platelet function appeared to be compromised, as indicated by aggregation studies using collagen and adenosine diphosphate as agonists. Product sterility was maintained.
There was no consensus of data supporting superior performance of one platelet storage container. This study indicates that canine platelet concentrates may be harvested by differential centrifugation of whole blood. In vitro studies utilizing three second-generation platelet storage bags support a previous study and concurs that canine platelet concentrates stored at 20-24° C using continuous agitation are viable for at least 5 days.Master of Science
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Bienz, Denise Edith. "Human blood platelets : the role of glycoproteins in the platelet interaction with thrombin and collagen /." [S.l.] : [s.n.], 1988. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Bateson, E. A. J. "Cryopreservation of platelets : investigation of factors affecting recovery and function of frozen and thawed platelets." Thesis, Open University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233520.
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Truss, Nicola Jane. "The effect of vascular cells on platelets and an assessment of platelet activity in clinical settings." Thesis, Queen Mary, University of London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511338.
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Li, Melissa. "Microfluidic system for thrombosis under multiple shear rates and platelet therapies." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/52154.
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Thrombosis is the pathological formation of platelet aggregates that cause stroke and heart attack\textemdash the leading causes of death in developed nations. Determining effective dosages for platelet therapies (e.g. aspirin, Integrilin, and Plavix) to prevent thrombosis is a persistent medical challenge (studies estimate up to 45% of patients exhibit insufficient responses to these drugs) and recent studies have implicated pathological flow conditions of high shear rates and stenosis morphology as primary factors. However, there are currently no diagnostic instruments able to recapitulate a range of such pathological flow conditions for evaluating thrombosis with and without these drugs.
In this work, a microfluidic device and associated optical system were designed and fabricated for simultaneous measurement of platelet aggregation at multiple initial wall shear rates within multiple stenotic channels in label-free whole blood and used to characterize thrombosis at varying dosages of two platelet therapies: acetyl-salicylic acid (aspirin) and eptifibatide (Integrilin).
Results from our studies show the effects of pathologically high shear rates on enhancing platelet thrombosis and demonstrate the widely varied, shear-dependent efficacy of each therapy. This study lays the foundation for the future development of a medical diagnostic for optimizing the type and dosage of patient platelet therapy and to better understand their mechanisms of action.
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Vanags, Daina M. "Adrenergic and serotonergic potentiation of platelet aggregation /." Title page, summary and contents only, 1993. http://web4.library.adelaide.edu.au/theses/09PH/09phv217.pdf.
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Sayeur, Mathieu. "Mechanical Modeling of Human Platelets Membrane." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32876.
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In an effort to help understand the mechanical properties of human platelets, their deformations were measured using micropipette experiments over an aspiration pressure range of 1-5 cmH2O, in steps of 1 cmH2O. The experiments confirmed the previously reported linear relationship between deformation and pressure. The experimental results were used to determine the material constants of a thin-axisymmetric shell model based on a strain-energy constitutive relation to describe the platelet deformations under aspiration. The model was successful in capturing the experimental deformations. It also suggested that the mechanical properties of human platelets are not significantly influenced by their volumes, but do vary depending on the platelets’ undeformed shape ratios. In addition, the model suggested that platelet membrane ruptures due to micropipette aspiration may be strain-related. The limitations of the experimental methods arising from direct contact with reactive cells such as platelets are highlighted, prompting the need for developing new methods which will not require the use of inhibition agents that alter the platelets’ mechanical properties.
Afin d’approfondir les connaissances des propriétés mécaniques des plaquettes humaines, leurs déformations ont été mesurées lors d’expériences avec des micropipettes pour des pressions d’aspiration de 1-5 cmH2O, par intervalles de 1 cmH2O. Les expériences ont confirmé la relation linéaire entre les déformations et la pression d’aspiration telle que précédemment publié. Les données expérimentales ont été utilisées pour déterminer les constantes matérielles d’un modèle de membrane mince axisymétrique basé sur une loi de comportement caractérisant l’énergie de déformation. Le modèle simule bien les déformations des plaquettes sous aspiration; il suggère également que les propriétés mécaniques des plaquettes humaines ne sont pas influencées significativement leur volume, mais varient en fonction de leurs formes avant déformation. De plus, le modèle suggère que les ruptures de la membrane des plaquettes sous aspiration seraient reliées aux déformations. Les limites des méthodes expérimentales utilisées, du fait du contact direct avec des cellules aussi réactives que les plaquettes sont soulignées, et mettent l’emphase sur le besoin de mettre au point de nouvelles méthodes ne requérant pas d’agents d’inhibitions qui altèrent les propriétés mécaniques des plaquettes.
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Inamdar, Vaishali Vijay. "FUNCTIONAL PROTEIN TYROSINE PHOSPHATASES IN PLATELETS." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/473257.
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Biomedical SciencesPh.D.
Platelets are small anucleate cells in blood that are derived from megakaryocytes and their primary function is to prevent bleeding. Upon vascular injury, the sub-endothelial collagen gets exposed to which platelets bind and aggregate eventually forming a platelet plug. There are several receptors on platelet surface that can be divided into two broad categories; the immune-receptor tyrosine-based activation motif (ITAM) and the G protein-coupled receptors (GPCRs). The role of several protein tyrosine kinases (PTKs) downstream of ITAM and GPCRs has been extensively studied. However, the role of protein tyrosine phosphatases (PTPs) have been under-investigated in platelets. PTPs are important for dephosphorylating and activating or inactivating the protein. Proteomics studies show presence of 10 receptor like and 10 cytoplasmic phosphatases in platelets. To date, only five non-transmembrane PTPs (NTPTPs), PTP-1B, Shp1, Shp2, LMW-PTP, MEG2-PTP and a one receptor- like PTP (RPTP), CD148,
Temple University--Theses
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Samiei, Mitra. "Characterization of protein kinases in platelets." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0025/NQ46416.pdf.
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Nyarko, Kwasi Agyepong. "Bovine platelets, activation and signaling mechanisms." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ58308.pdf.
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Comfurius, Paul. "Phospholipid flip-flop in activated platelets." [Maastricht : Maastricht : Rijksuniversiteit Limburg] ; University Library, Maastricht University [Host], 1989. http://arno.unimaas.nl/show.cgi?fid=5515.
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Ding, Y.-A. "Angiotensin II receptors in human platelets." Thesis, University of Glasgow, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.372369.
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Grunkemeier, John M. "Effect of adhesion proteins and surface chemistry on the procoagulant state of adherent platelets /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8087.
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Lisiak, Karolina. "The role of platelets in the activation of TAFI in model thrombi." Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2008. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=24805.
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Coimbra, Leila Santana. "Influência de drogas antiplaquetárias na reparação da doença periodontal experimental em ratos /." Araraquara : [s.n.], 2010. http://hdl.handle.net/11449/95389.
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Orientador: Luís Carlos SpolidorioBanca: Joni Augusto Cirelli
Banca: Raquel Fernanda Gerlach
Resumo: O objetivo deste trabalho foi avaliar o efeito da administracao da aspirina (Asp), do clopidogrel (Clo) e da ticlopidina (Tic) sobre o processo de reparacao dos tecidos periodontais apos inducao experimental de periodontite em ratos. Primeiramente avaliou-se a acao destas drogas sobre a expressao das citocinas pro-inflamatorias: TNF-α, IL-6 e TXA2 no tecido gengival de 25 ratos subdivididos em 5 grupos (n=5), 15 dias apos a instalacao da ligadura ao redor do primeiro molar inferior. Para avaliacao do reparo dos tecidos periodontais, setenta e dois ratos (Rattus norvegicus albinus, Holtzman) foram distribuídos aleatoriamente em 6 grupos (n=12), sendo 1 controle e 5 submetidos a periodontite atraves da instalacao de ligadura bilateral na regiao de primeiro molar inferior. Apos 15 dias, o grupo controle e um grupo com periodontite foram sacrificados. Para a inducao do reparo dos tecidos periodontais, as ligaduras dos animais dos outros 4 grupos foram removidas e os ratos foram tratados com solucao de NaCl 0.9%, Asp (30mg/kg), Clo (75 mg/kg) e Tic (300 mg/kg), diariamente, via gavagem. Apos 15 dias de tratamento, os animais foram sacrificados, as hemi- mandibulas do lado direito removidas para analise histologica e as do lado esquerdo para avaliacao macroscopica, microtomografia computadorizada e analise da expressao, atividade especifica e co-localizacao das metaloproteinases de matriz (MMPs) -2 e -9 atraves de zimograma e zimografia in situ. Apos a retirada da ligadura, houve reparacao do osso alveolar e reparacao do tecido gengival representado pela recomposicao da arquitetura tecidual do epitélio e do tecido conjuntivo. O tratamento com Asp comprometeu a reparacao óssea alveolar na face mesial e acelerou na area de furca, ao passo que nao influenciou na recomposicao da arquitetura do tecido epitelial e... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The aim of this study was to evaluate the effect of administration of aspirin (Asp), clopidogrel (Clo) and ticlopidine (Tic) in the process of periodontal tissue repair after induction of experimental periodontitis in rats. First, we evaluated the action of these drugs on the expression of pro-inflammatory cytokines: TNF-α, IL-6 and TXA2 in the gingival tissue of 25 rats randomly distributed in five equal groups (n=5), 15 days after ligature placement around lower first molars. For periodontal tissue evaluation, seventy-two rats (Rattus norvegicus albinus, Holtzman) were randomly distributed in 6 equal groups (n=12). One control and 5 submitted to a ligature-induced periodontitis model in the region of lower first molar bilaterally. After 15 days, the control group and a group with periodontitis were sacrificed. To induce periodontal tissue repair, ligatures from the other 4 groups were removed and the rats treated with NaCl 0.9%, Asp (30 mg/kg), Clo (75 mg/kg) and Tic (300 mg/kg) daily by gavage. After 15 days of treatment, animals were killed, the right mandibles were removed for histological analysis and the left side to macroscopic, microtomography evaluation and expression, activity and colocalization of matrix metalloproteinases (MMPs) -2 and -9 by zymogram and in situ zymography. After removal of the ligature, there was repair of the alveolar bone and gingival tissue represented by the restoration of tissue architecture of the epithelium and connective tissue. Treatment with Asp undertook the repair of the mesial alveolar bone and accelerated the repair of furcation area, while not influenced the restoration of tissue architecture and epithelial tissue. Treatment with Tic undertook the repair of mesial alveolar bone and furcation the area, as well as the repair of gingival epithelial... (Complete abstract, click electronic access below)
Mestre
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Hartley, Paul Steven. "Factors affecting the viability of human platelets." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/24685.
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Human platelets die in vitro in a caspase-independent manner with features of necrosis. Little is known about the factors affecting the mode of platelet death nor how death is brought about. This thesis aimed to generate novel tools for the discrimination of live from dead platelets and to evaluate the role of autophagy, temperature and sugar metabolism in the demise of platelets in vitro. Three dyes, 10-nonyl acridine orange, calcein and FM 4-64 were found to be useful for the evaluation of platelet viability. It was found that during in vitro storage dead platelets formed metalloproteinase-dependent aggregates and shed CD42b. Platelets died more slowly at ambient temperature than at 37°C and appeared to arrest in death when kept at 4°C. Cold-stored platelets remained viable for ten days but whereupon transfer to 37°C they died rapidly. Platelets did not rely on exogenous glucose for viability but hypoglycaemia sensitised them to pro-apoptotic stimuli. Inhibitors of glycogen breakdown were toxic to platelets, implicating glycogen in the maintenance of platelet viability in vitro. Autophagy could not be implicated in the loss of platelet viability but data suggested a role for crinophagy in the maintenance of platelet function.
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Kamath, Sridhar. "A study of platelets in atrial fibrillation." Thesis, University of Birmingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270055.
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Zagai, Ulrika. "Platelets and eosinophils in lung tissue remodelling /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-841-X/.
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Webb, Rachel J. "Characterisation of P2-receptors on human platelets." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342989.
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Marshall, Stuart J. "GPIb-mediated tyrosine phosphorylation in human platelets." Thesis, University of Oxford, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275467.
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Fulkerson, Zachary Bennett. "LYSOPHOSPHATIDIC ACID PRODUCTION AND SIGNALING IN PLATELETS." UKnowledge, 2011. http://uknowledge.uky.edu/physiology_etds/1.
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Lysophosphatidic acid (LPA) belongs to a class of extracellular lipid signaling molecules. In the vasculature, LPA may regulate platelet activation and modulate endothelial and smooth muscle cell function. LPA has therefore been proposed as a mediator of cardiovascular disease.
The bulk of circulating LPA is produced from plasma lysophosphatidylcholine (LPC) by autotaxin (ATX), a secreted lysophospholipase D (lysoPLD). Early studies suggest that some of the production of circulating LPA is platelet-dependent. ATX possesses an N-terminal somatomedin B-like domain suggesting the hypothesis that ATX interacts with platelet integrins which may localize ATX to substrate in the membrane and/or alter the catalytic activity of ATX. Using static adhesion and soluble binding assays we found that ATX does indeed bind to platelets and cultured mammalian cells in an integrin-dependent manner which is blocked by integrin function-blocking peptides and antibodies. This binding increases both the activity of ATX and localization of its product, LPA, to the platelet/cell membrane.
LPA is generally stimulatory to human platelets although platelets from a small population of donors are refractory to LPA stimulation. Likewise LPA is inhibitory to murine platelets. We previously found that LPA receptor pan-antagonists reduce agonist-induced platelet activation, and partial stimulation of LPA5 specifically increases platelet activation in humans. Since both LPA5 and LPA4 are present at significant levels in human platelets, we hypothesized that LPA4 is responsible for an inhibitory pathway and LPA5 is responsible for an inhibitory pathway. We used mice deficient in LPA4 to test this model. Isolated platelet function tests revealed no major difference between lpa4-/- mice compared with WT mice although lpa4-/- mice were more prone to FeCl3-induced thrombosis. Paradoxically, chimeric mice reconstituted with lpa4-/- deficient bone marrow derived cells were protected from thrombosis. These discrepancies may be explained by involvement of endothelial cells and the relative scarcity of LPA receptors in murine platelets compared with human platelets.
Taken together, these results demonstrate two critical regulators of LPA signaling and open up new avenues to further our understanding of atherothrombosis.
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Peters, Mark John. "The role of platelets in acute inflammation." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271069.
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