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Platelet Membrane (platelet + membrane)
Terms modified by Platelet Membrane Selected AbstractsCoagulation dynamics and platelet functions in obstructive jaundiced patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2009Tebessüm Çak Abstract Background:, All of the body systems are affected by increased levels of bilirubin. The aim of this study is to investigate the function of platelets and clotting dynamics in patients with obstructive jaundice. Methods:, Liver function tests, serum CRP, PT, PTT and hemogram were measured in 23 patients with obstructive jaundice. Thromboelastography (TEG) was done for the evaluation of coagulation dynamics, while platelet function assay (PFA 100) was used to evaluate platelet functions. Blood samples were obtained at two occasions, before the drainage and 3 weeks after the relief of the obstruction. Results:, Hypercoagulation was detected in 80% of patients. Maximum strength, elasticity, coagulation indices of the clot were correlated with increased concentrations of direct bilirubin. Although maximum strength of coagulum usually represents increased activity of platelet function, membrane closure times with PFA 100 were found to be prolonged in 30% of patients, reduced values were determined in 17% of patients. No demonstrable effect on coagulation parameters and platelet function were detected after drainage procedures regardless of modality. Conclusions:, Even though there is a general assumption about the increased bleeding tendency in obstructive jaundiced patients, we could not demonstrate reduced clotting activity by measuring with either PFA or TEG. On the contrary we observed tendency for hypercoagulation independent of increased prothrombin times. The most probable cause of this effect is the increased activity of fibrin polymers on platelet membrane. [source] Plasma serotonin levels and the platelet serotonin transporterJOURNAL OF NEUROCHEMISTRY, Issue 1 2007B. Brenner Abstract Serotonin (5HT) is a platelet-stored vasoconstrictor. Altered concentrations of circulating 5HT are implicated in several pathologic conditions, including hypertension. The actions of 5HT are mediated by different types of receptors and terminated by a single 5HT transporter (SERT). Therefore, SERT is a major mechanism that regulates plasma 5HT levels to prevent vasoconstriction and thereby secure a stable blood flow. In this study, the response of platelet SERT to the plasma 5HT levels was examined within two models: (i) in subjects with chronic hypertension or normotension; (ii) on platelets isolated from normotensive subjects and pretreated with 5HT at various concentrations. The platelet 5HT uptake rates were lower during hypertension due to a decrease in Vmax with a similar Km; also, the decrease in Vmax was primarily due to a decrease in the density of SERT on the platelet membrane, with no change in whole cell expression. Additionally, while the platelet 5HT content decreased 33%, the plasma 5HT content increased 33%. Furthermore, exogenous 5HT altered the 5HT uptake rates by changing the density of SERT molecules on the plasma membrane in a biphasic manner. Therefore, we hypothesize that in a hypertensive state, the elevated plasma 5HT levels induces a loss in 5HT uptake function in platelets via a decrease in the density of SERT molecules on the plasma membrane. Through the feedback effect of this proposed mechanism, plasma 5HT controls its own concentration levels by modulating the uptake properties of platelet SERT. [source] Glycoprotein (GP) VI dimer as a major collagen-binding site of native platelets: direct evidence obtained with dimeric GPVI-specific FabsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2009S. M. JUNG Summary.,Background: The platelet collagen receptor glycoprotein (GP) VI is suggested to exist as a dimer on the platelet surface, but no direct proof of the functional importance of dimer formation has been provided. Objectives: To obtain direct evidence for GPVI dimers on the platelet membrane and their functional importance, Fab antibodies were developed that bind to GPVI dimer (GPVI-Fc2) but not to GPVI monomer (GPVIex) through a phage display method. Results: Ssix Fabs were found: B,F, only reactive with GPVI-Fc2, and A, mainly reactive with GPVI-Fc2, with some reactivity towards GPVIex; each Fab (Fab-dHLX-MH) forms a bivalent dimer (b-Fab) by dimerizing the dHLX domains from two Fab molecules. Fab F was subcloned to a monovalent format by deleting its dHLX domain. All b-Fabs induced platelet aggregation, but the monomeric form of Fab F (m-Fab-F) specifically inhibited collagen-induced aggregation. All b-Fabs and m-Fab-F inhibited GPVI-Fc2 binding to fibrous collagen. Immunoblotting showed that b-Fab-F and m-Fab-F bound weakly to GPVI-Fc2. Adding the anti-GPVI monoclonal antibody 204-11 increased the Bmax of m-Fab-F binding to GPVI-Fc2, suggesting that 204-11 binds to GPVI-Fc2 molecules not already in the appropriate conformation to recognize the Fab, converting them to a conformation reactive to the Fab. Conclusions: GPVI forms a specific structure by dimerization that is necessary for the binding of this receptor to collagen fibrils. The binding of m-Fab-F to platelets directly demonstrates that GPVI is present as a functionally relevant dimer on the platelet surface. [source] Differential response of platelets to chemokines: RANTES non-competitively inhibits stimulatory effect of SDF-1,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2004B. Shenkman Summary.,Background:,Among the chemokines related to CXC and CC receptor groups and released from platelets, leukocytes and endothelial cells, SDF-1, TARC and MDC have been found to be platelet agonists. Platelets do not contain SDF-1,. In contrast, RANTES is constitutively present in platelet ,-granules and released upon platelet activation. Objectives:,To study a possible role of RANTES as a modulator of SDF-1, effect on platelets, in relation to CXCR4 and various CC receptors. Methods:,CXCR-4 (CXCL12) receptor expression and platelet activation were evaluated by flow cytometry, platelet deposition was studied by cone and plate(let) analyzer, and platelet aggregation by turbidometric aggregometry. Results:,Flow cytometry studies revealed similar expression of CXCR-4, the specific receptor of SDF-1, on intact, inactivated, and activated platelets. Preincubation of platelets with RANTES affected neither CXCR-4 expression, nor SDF-1, binding to the platelet membrane. In the presence of fibrinogen, SDF-1, activated gel-filtered platelets. RANTES did not activate platelets, but substantially (by 70%) inhibited SDF-1,-induced fibrinogen binding. Similarly, RANTES abrogated the promoting effect of SDF-1, on whole blood platelet adhesion to endothelial cell monolayer under venous flow conditions. In platelet-rich plasma, RANTES moderately inhibited SDF-1,-induced platelet aggregation, while it did not affect aggregation induced by thrombin-receptor activation peptide, adenosine diphosphate, or phorbol 12-myristate 13-acetate. A synergistic inhibitory effect of RANTES and prostaglandin E1 used at subthreshold concentrations, on SDF-1,-induced aggregation and SDF-1,-induced fibrinogen binding to platelets was observed, which may suggest involvement of RANTES in a cAMP-dependent signal transduction pathway. Conclusions:,RANTES non-competitively inhibits activation of platelets by SDF-1,, and thus may play a regulatory role in platelet response to inflammation. [source] Effects of ,-endorphin and met-enkephalin on platelet activityAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2001Angelo Tirelli Abstract In the present study, ,-endorphin and met-enkephalin were tested for their antiplatelet activity in human platelet-rich plasma (PRP). Blood samples were obtained from 15 healthy subjects. The results of the study show that these two endogenous opioids (200 pg/ml final concentration) reduce platelet aggregation when it is induced by ADP at low dose (0.5 ,M). It is likely due to conformational changes on the platelet membrane that cause a non-specific decreased susceptibility to platelet-aggregating agonists. Am. J. Hematol. 68:1,3, 2001. © 2001 Wiley-Liss, Inc. [source] The role of insulin as an antithrombotic humoral factorBIOESSAYS, Issue 1 2004Kushal Chakraborty Insulin is well known for its essential role in carbohydrate metabolism: insulin deficiency results in the development of diabetes mellitus. It has been known for many years that people with diabetes mellitus are predisposed to develop thrombotic diseases including myocardial infarction. It was thought that the thrombus formation was the consequence of impaired carbohydrate metabolism. In recent years, it has become apparent that insulin is capable of ameliorating several pathophysiological events, leading to the inhibition and dissolution of the formed thrombus in the system. These insulin-induced events include inhibition of platelet aggregation by prompting the synthesis of NO in platelet and prostacyclin in endothelial cells. Furthermore, insulin upregulates prostacyclin receptors and downregulates ,2 adrenergic receptor in platelets, thereby amplifying the inhibition of platelet aggregation. Insulin also releases tissue plasminogen activator, a potent thrombolytic enzyme, from the platelet membrane which dissolves the formed thrombus leading to the resumption of normal blood circulation. In effect, insulin could be an essential tool in the control of thrombotic disorders. BioEssays 26:91,98, 2004. © 2003 Wiley Periodicals, Inc. [source] Gestational diabetes affects platelet behaviour through modified oxidative radical metabolismDIABETIC MEDICINE, Issue 1 2004L. Mazzanti Abstract Aims Patients with Type 1 and Type 2 diabetes mellitus show altered platelet function including decreased nitric oxide synthase (NOS) activity and increased peroxynitrite production. Gestational diabetes mellitus (GDM) is a clinical condition which is ideal for evaluating short-term effects of impaired glucose metabolism, ruling out the possibility that the platelet abnormalities are a consequence of diabetic complications. The aim of the present work was to study NO metabolism in platelets from pregnant women with GDM. The production of peroxides was also studied as it is strongly involved in peroxynitrite formation. Methods Platelet NOS activity and peroxynitrite production, levels of hydroperoxides and thiobarbituric acid reactive substances (TBARS) in platelet membranes in the basal state and after in vitro peroxidative stress with phenylhydrazine were determined in 40 pregnant women with GDM, 40 healthy pregnant women (pregnant controls) of comparable age and gestational age, and 15 healthy non-pregnant women (controls). Results NOS activity was significantly increased in both groups of pregnant women compared with non-pregnant ones, and in GDM women compared with pregnant controls. Production of peroxynitrite was higher in GDM women than in pregnant controls, who also had significantly reduced production compared with non-pregnant women. Basal levels of peroxidation of the platelet membranes evaluated either by hydroperoxide content and TBARS levels or the susceptibility to peroxidation were increased in GDM patients in comparison with both control groups. Conclusions We have shown a modification in platelet NO and peroxynitrite production and an increase in platelet indicators of oxidative stress in GDM women compared with healthy pregnant women which might be at the basis of a cellular dysfunction. [source] Platelets are mitogenic for periosteum-derived cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2003Reinhard Gruber Abstract The early stages of bone regeneration are associated with a high mitogenic activity of periosteal cells. Here we addressed the question of whether platelets that accumulate within the developing haematoma can account for this tissue response. Addition of platelets, platelet-released supernatants, platelet membranes, and microparticles to bovine periosteum-derived cells resulted in an increase in 3H-thymidine incorporation; lipid extracts had no effect. Platelet-released supernatants retained their activity after incubation at 56°C, but not at 100°C. Gel chromatographic analysis revealed the highest mitogenic activity at approximately 35 kD. Of the factors released from activated platelets, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) increased 3H-thymidine incorporation. The mitogenic activity of platelet-released supernatants was decreased by anti-PDGF, and anti-bFGF antibodies. Platelet-released supernatants increased the number of proliferating periosteum-derived cells as determined by the expression pattern of Ki67. Platelet-released supernatants also resulted in a stimulation of cell proliferation in periosteal explants. These results suggest that platelets have the potential to stimulate the mitogenic response of the periosteum during bone repair. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Platelet adhesion to dimeric ,2 -glycoprotein I under conditions of flow is mediated by at least two receptors: glycoprotein Ib, and apolipoprotein E receptor 2,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2007M. T. T. PENNINGS Summary.,Background: The major antigen implicated in the antiphospholipid syndrome is beta2-glycoprotein I (,2GPI). Dimerized ,2GPI binds to apolipoprotein E receptor 2, (apoER2,) on platelets and increases platelet adhesion to collagen under conditions of flow. Aim: To investigate whether the interaction between dimerized ,2GPI and platelets is sufficiently strong to resist shear stresses. Methods: We studied the interaction of platelets with immobilized dimerized ,2GPI under conditions of flow, and further analyzed the interaction using surface plasmon resonance and solid phase immunoassays. Results: We found that dimerized ,2GPI supports platelet adhesion and aggregate formation under venous flow conditions. Adhesion of platelets to dimerized ,2GPI was completely inhibited by the addition of soluble forms of both apoER2, and GPIb,, and the addition of receptor-associated protein and the removal of GPIb, from the platelet surface. GPIb, co-precipitated with apoER2,, suggesting the presence of complexes between GPIb, and apoER2, on platelet membranes. The interaction between GPIb, and dimeric ,2GPI was of intermediate affinity (Kd = 180 nm) and Zn2+, but not Ca2+ -dependent. Deletion of domain V from dimeric ,2GPI strongly reduced its binding to both GPIb, and apoER2,. Antibodies that inhibit the binding of thrombin to GPIb, inhibited platelet adhesion to dimeric ,2GPI completely, while antibodies blocking the binding of von Willebrand factor to GPIb, had no effect. Dimeric ,2GPI showed reduced binding to low-sulfated GPIb, compared to the fully sulfated form. Conclusion: We show that platelets adhere to dimeric ,2GPI under both arterial and venous shear stresses. Platelets adhere via two receptors: GPIb, and apoER2,. These receptors are present in a complex on the platelet surface. [source] Substitutes and alternatives to platelet transfusions in thrombocytopenic patientsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2003M. A. Blajchman Summary., Over the past decade, there have been many improvements in both the safety profile and quality of liquid-stored allogeneic platelet concentrates. However, significant problems with the clinical use of such products remain. Efforts to overcome some of these have resulted in the development of an array of novel therapeutic strategies for the manufacture of platelet products and platelet substitutes, as well as other approaches using alternatives to platelet concentrates. These various products or procedures are at various stages of clinical development. This review summarizes some recent advancements in the preparation of liquid and frozen stored platelets, as well as approaches used for the pathogen inactivation of platelets. Thus, the status of lyophilized platelets, infusible platelet membranes, red blood cells (RBCs) bearing RGD ligands, fibrinogen-coated albumin microcapsules, and liposome-based agents are discussed. Pre-clinical studies and phase 1,3 clinical trials have been encouraging for several of these; however, to date, very few have been licensed for clinical use. Potential alternatives to allogeneic platelet transfusions including correction of anemia by RBC transfusions, recombinant activated factor VII and HLA-reduced platelets are also reviewed. With the ongoing technical and scientific development of such diverse products, those properties that may be necessary for such agents to have hemostatic efficacy will become apparent. However, safety and efficacy must be demonstrable in preclinical studies and clinical trials, before novel platelet concentrates, platelet substitutes and alternatives to platelets can be used in patients with thrombocytopenia. [source] Pharmacology and autoradiography of human DP prostanoid receptors using [3H]-BWA868C, a DP receptor-selective antagonist radioligandBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2000N A Sharif A potent and highly selective DP prostanoid receptor antagonist radioligand, [3H]-cyclohexyl-N-BWA868C (3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2-hydroxyethyl-amino) hydantoin, ([3H]-BWA868C)), has been generated for receptor binding and autoradiographic studies. Specific [3H]-BWA868C binding to human platelet membranes achieved equilibrium within 60 min at 23°C and constituted up to 95% of the total binding. The association (K+1) and dissociation (K,1) rate constants of binding were 0.758±0.064 min,1, mmol and 0.0042±0.0002 min,1, respectively, yielding dissociation constants (KDs) of 5.66±0.44 nM (n=4). Specific [3H]-BWA868C bound to DP receptors with a high affinity (KD=1.45±0.01 nM, n=3) and to a finite, saturable number of binding sites (Bmax=21.1±0.6 nmol g,1 wet weight). DP receptor class prostanoids (e.g. ZK118182, BW245C, BWA868C, PGD2) exhibited high (nanomolar) affinities for [3H]-BWA868C binding, while prostanoids selective for EP, FP, IP and TP receptors showed a low (micromolar) affinity. Specific DP receptor binding sites were autoradiographically localized on the ciliary epithelium/process, longitudinal and circular ciliary muscles, retinal choroid and iris in human eye sections using [3H]-BWA868C. While [3H]-PGD2 yielded similar quantitative distribution of DP receptors as [3H]-BWA868C, the level of non-specific binding observed with [3H]-PGD2 was significantly greater than that observed with [3H]-BWA868C. It is concluded that [3H]-BWA868C is a high-affinity and very specific DP receptor radioligand capable of selectively labelling the DP receptor. [3H]-BWA868C may prove useful for future homogenate-based and autoradiographic studies on the DP receptor. British Journal of Pharmacology (2000) 131, 1025,1038; doi:10.1038/sj.bjp.0703686 [source] | |||||||||||||