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Sample records for platelet aggregation system

  1. 21 CFR 864.5700 - Automated platelet aggregation system.

    Science.gov (United States)

    2010-04-01

    ... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet...

  2. Platelet activation and aggregation

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

  3. Platelet aggregation following trauma

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...

  4. Novel aspects of platelet aggregation

    Directory of Open Access Journals (Sweden)

    Roka-Moya Y. M.

    2014-01-01

    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.

  5. Cyclosporine A enhances platelet aggregation.

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    Grace, A A; Barradas, M A; Mikhailidis, D P; Jeremy, J Y; Moorhead, J F; Sweny, P; Dandona, P

    1987-12-01

    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.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...

  7. Analysis of aggregation of platelets in thrombosis

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    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.

  8. BETA-ADRENOBLOCKERS AND PLATELET AGGREGATION. CARVEDILOL

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    A. N. Zakirova

    2008-01-01

    Full Text Available Approaches evolution to studying of beta-blockers influence on platelet aggregation is reviewed. The current view on of beta-blocker antiplatelet effects is presented on the basis of physical and chemical drug properties (water repellency, dipole moment, molecular mass. Trail results on carvedilol influence on platelet aggregation are focused.

  9. 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))

    1987-11-01

    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.

  10. Different training schedules influence platelet aggregation in show jumping horses.

    Science.gov (United States)

    Giannetto, C; Arfuso, F; Fazio, F; Giudice, E; Pietro, S Di; Bruschetta, D; Piccione, G

    2017-03-28

    Depending on the intensity, duration and type of physical exercise, equine metabolism has to adapt to nervous, cardiovascular, endocrine and respiratory system requirements. In horses, exercise and training are known to have considerable effects on the mechanisms of hemostatic system involving platelet activity. The aim of the present study was to evaluate the effect of different training schedules on platelet aggregation in 15 Italian Saddle jumping horses. Animals were divided into three equal groups: Group A was subjected to a high intensity-training program; group B to a light training program, group C included sedentary horses. From each animal, blood samples were collected by jugular venipuncture at rest on the 1st, 3rd and 5th days, and afterwards, once a week, for a total of 5 weeks data recording, in order to assess the maximum degree of platelet aggregation and the initial velocity of aggregation (slope) platelet aggregation. Two-way analysis of variance (ANOVA) showed a significant effect of the different training schedules on studied parameters. The results revealed a different degree of platelet aggregation and a different initial velocity of platelet aggregation that changes during the different training schedules in horses that could represent a different protective endothelial mechanism. These findings could have an important role for a clearer knowledge of the physiological reference values of platelet aggregation and for a better interpretation of these variations during the training.

  11. Mapuche herbal medicine inhibits blood platelet aggregation.

    Science.gov (United States)

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM) and collagen- (2.0 μg/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H(2)O), Amomyrtus luma (DCM : MeOH 1 : 1) and Cestrum parqui (DCM : MeOH 1 : 1). The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1), and L. apiculata (H(2)O) were substantial and confirmed by inhibition of platelet surface activation markers.

  12. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    Directory of Open Access Journals (Sweden)

    Susan Skanderup Falkenberg

    2012-01-01

    Full Text Available 12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM and collagen- (2.0 μg/mL induced aggregations in human blood. These four species in respective extracts (in brackets were Blechnum chilense (MeOH, Luma apiculata (H2O, Amomyrtus luma (DCM : MeOH 1 : 1 and Cestrum parqui (DCM : MeOH 1 : 1. The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1, and L. apiculata (H2O were substantial and confirmed by inhibition of platelet surface activation markers.

  13. Nanoparticle-induced platelet aggregation and vascular thrombosis.

    Science.gov (United States)

    Radomski, Anna; Jurasz, Paul; Alonso-Escolano, David; Drews, Magdalena; Morandi, Maria; Malinski, Tadeusz; Radomski, Marek W

    2005-11-01

    Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2-300 microg ml(-1)) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4 microm). Platelet function was studied using lumi aggregometry, phase-contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCN>or=SWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane-, ADP, matrix metalloproteinase- and protein kinase C-dependent pathways of aggregation. Furthermore, particle-induced aggregation was inhibited by prostacyclin and S-nitroso-glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter.

  14. Evaluation of platelet aggregation in platelet concentrates: storage implications

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    Neiva Teresinha J.C.

    2003-01-01

    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.

  15. Platelet aggregation secondary to coronary obstruction.

    Science.gov (United States)

    Moore, S

    1976-03-01

    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

  16. [A method for studying intravascular platelet aggregation in vitro].

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    Ikonnikova, E I; Chernousova, L A; Moshkina, I R

    1999-06-01

    A simple available method for evaluating intravascular platelet aggregation is proposed. It consists in graphic recording of disaggregation of platelet-rich citrate plasma, which indicates the degree of intravascular aggregation. Intravascular aggregation is notably increased in coronary patients and negligible in normal subjects. The method may be used for the diagnosis of diseases with a high thrombogenic risk.

  17. Platelet aggregation and quality control of platelet concentrates produced in the Amazon Blood Bank

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    Maria José Dantas Coêlho

    2011-01-01

    Full Text Available BACKGROUND: The study of platelet aggregation is essential to assess in vitro platelet function by different platelet activation pathways. OBJECTIVE: To assess aggregation and biochemical parameters of random platelet concentrates produced at the Fundação HEMOAM using the quality control tests defined by law. METHODS: Whole blood samples from 80 donors and the respective platelet concentrate units were tested. Platelet concentrates were tested (platelet count, aggregation and pH on days 1, 3 and 5 of storage. Additionally a leukocyte count was done only on day 1 and microbiological tests on day 5 of storage. Collagen and adenosine diphosphate were used as inducing agonists for platelet aggregation testing. RESULTS: Donor whole blood had normal aggregation (aggregation with adenosine diphosphate = 67% and with collagen = 78%. The median aggregation in platelet concentrates with adenosine diphosphate was low throughout storage (18% on day 1, 7% on day 3 and 6% on day 5 and the median aggregation with collagen was normal only on day 1 and low thereafter (54.4% on day 1, 20.5% on day 3 and 9% on day 5. CONCLUSION: Although the results were within the norms required by law, platelet concentrates had low aggregation rates. We suggest the inclusion of a functional assessment test for the quality control of platelet concentrates for a more effective response to platelet replacement therapy.

  18. Platelet aggregation associated with ethanol intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Volk, S.; Walenga, J.; Fareed, J.; Schumacher, H. (Loyola Univ. Medical Center, Maywood, IL (USA))

    1989-02-09

    Alcohol is known to produce profound effects on blood; during chronic intoxication, prolongation of bleeding time has been reported. Utilizing human platelet rich plasma, we have studied the effect of alcohol on epinephrine, arachidonic acid and ADP induced aggregation. Control responses were obtained with saline from which the relative inhibition by alcohol was calculated. These studies were carried out at a concentration of 1.25-5.0 mg/ml which represents 0.125-0.5% alcohol blood levels. From 25 normal male and female volunteers, without prior hemostatic defects or drug ingestion, a dose-dependent inhibition by alcohol of all three agonist induced aggregations was noted. Alcohol itself did not produce any aggregation response. These studies demonstrate that alcohol at levels which are reached during intoxication is capable of impairing platelet function. The implication of this finding on the bleeding complications in healthy intoxicated patients may be significant during traumatic events, and individuals taking antiplatelet drugs may present a more serious hemostatic deficit during alcohol intoxication.

  19. [Mechanism of cooked blanched garlic leaves against platelet aggregation].

    Science.gov (United States)

    Wang, Xin-Hua; Di, Yan-Hui

    2014-06-01

    This study was purposed to explore the mechanism of cooked blanched garlic leave juice against platelet aggregation. The juice of blanched garlic leaves was mixed with platelet rich plasma (PRP), the human platelet aggregation, the activation of human platelets induced by adenosine diphosphate (ADP) and collagen were observed; the expression levels of the activated platelets (Fib-R) and P-selectin (CD62P), and the amount of platelet fibrinogen binding were detected by flow cytometry; 10 rabbits were randomly divided into two groups, in addition to the normal diet, they were fed with physiologic saline and cooked blanched garlic leave juice respectively. After 1, 3, 5 , 8 weeks, the maximum ratio of rabbit platelet aggregation induced by ADP and collagen were observed . The results showed that the cooked blanched garlic leave juice could significantly inhibit human platelet aggregation induced by ADP and collagen (P 0.05), but was able to inhibit platelet fibrinogen binding capacity (P garlic leave juice was significantly lower than that in control group (P garlic leave juice can inhibit platelet aggregation in vitro and in vivo, the inhibition of aggregation pathway mainly is blocking the combination of fibrinogen with Fib-R, which finally results in the inhibition of platelet aggregation. Therefore, regular consumption of cooked blanched garlic leaves may prevent cardiovascular thrombotic diseases.

  20. Effect of supine exercise on platelet aggregation and fibrinolytic activity

    DEFF Research Database (Denmark)

    Dag, B; Fornitz, Gitte Gleerup; Bak, A M

    1994-01-01

    In 12 healthy young men, strenuous cycling exercise in the supine position, caused platelet aggregability to decrease and the ADP threshold to rise from 7.0 microM resting, to 9.5 exercising (P ... from 178 to 68 min, PAI-1 fell from 8.91 to 5.16 IU ml-1, and t-PA rose from 0.56 to 3.95 IU ml-1, all three values were significant to P exercise, it did not increase platelet activity as expected, but caused a modest increase...... of fibrinolytic activity. These results suggest that supine exercise will not affect the haemostatic system adversely....

  1. Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation.

    Science.gov (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

    2016-04-01

    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.

  2. Effects of hormones on platelet aggregation.

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

    2014-04-01

    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.

  3. Increased platelet aggregability following an atherogenic diet in rabbits

    OpenAIRE

    Velkovski Saško D.; Mazić Sanja; Nešić Dejan M.; Igrački Iva; Milošević Verica L.; Starčević Vesna P.

    2002-01-01

    In atherosclerosis researches different animal models are used but the most common is the rabbit, because of the easy development of atherosclerotic lesions. Atherosclerosis is a multicellular process and platelets play an important role in atherogenesis. Excessive plasma lipids stimulate platelet aggregability and thus atherosclerosis development. The effects of an atherogenic diet on lipid status, abdominal aorta wall structure, and platelet aggregability were studied in rabbits. Adult male...

  4. The automation of routine light transmission platelet aggregation

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    Lawrie, A S; Kobayashi, K; Lane, P J; Mackie, I J; Machin, S J

    2014-01-01

    Introduction The investigation of platelet function by aggregometry requires specialist equipment and is labour intensive. We have developed an automated platelet aggregation method on a routine coagulation analyser. Methods We used a CS-2000i (Sysmex) with prototype software to perform aggregation in platelet-rich plasma (PRP), using the following agonists: ADP (0.5–10 μm), epinephrine (0.5–10 μm), collagen (0.5–10 mg/μL), ristocetin (0.75–1.25 mg/mL) and arachidonic acid (0.12–1.0 mm). Platelet agonists were from Hyphen Biomed, and an AggRAM aggregometer (Helena Biosciences) was used as the reference instrument. Results CS-2000i reaction cuvette stirrer speed was found to influence reaction sensitivity and was optimized to 800 rpm. There were no clinically significant changes in aggregation response when the PRP platelet count was 150–480 x 109/L, but below this there were changes in the maximum amplitude (MA) and slope (rate). Dose response with each of the agonists was comparable between CS-2000i and an AggRAM aggregometer and normal subjects receiving antiplatelet drugs. Aggregation imprecision was similar on both the CS-2000i and AggRAM systems, with a cv for 2–5 μm ADP MA and slope varying between 3–12%. Conclusion Our preliminary studies indicated that optimal sensitivity using the CS-2000i was obtained with a reaction cuvette stirrer speed of 800 rpm and a PRP platelet count of 200–300 x 109/L; aggregation with a PRP count <100 x 109/L showed poor sensitivity. Imprecision and detection of antiplatelet drug effects was similar between the CS-2000i and AggRAM. These data demonstrate that CS-2000i is comparable to a stand-alone aggregometer, although CS-2000i has the advantages of walk-away technology and also required a smaller sample volume than the AggRAM (44% less). PMID:24237750

  5. Effects of Suilysin on Streptococcus suis-induced platelet aggregation

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    Shengwei Zhang

    2016-10-01

    Full Text Available Blood platelets play important roles during pathological thrombocytopenia in streptococcal toxic shock syndrome (STSS. Streptococcus suis (S. suis an emerging human pathogen, can cause STSS similarly to S. pyogenes. However, S. suis interactions with platelets are poorly understood. Here, we found that suilysin (SLY, different from other bacterial cholesterol-dependent cytolysins (CDCs, was the sole stimulus that induced platelet aggregation. Furthermore, the inside-out activation of GPIIb/IIIa of platelets mediated SLY-induced platelet aggregation. This process was triggered by Ca2+ influx that depend on the pore forming on platelets by SLY. Additionally, although SLY induced α-granule release occurred via the MLCK-dependent pathway, PLC-β-IP3/DAG-MLCK and Rho-ROCK-MLCK signaling were not involved in SLY-induced platelet aggregation. Interestingly, the pore dependent Ca2+ influx was also found to participate in the induction of platelet aggregation with pneumolysin (PLY and streptolysin O (SLO, two other CDCs. It is possible that the CDC-mediated platelet aggregation we observed in S. suis is a similar response mechanism to that used by a wide range of bacteria. These findings might lead to the discovery of potential therapeutic targets for S. suis-associated STSS.

  6. Effects of Suilysin on Streptococcus suis-Induced Platelet Aggregation

    Science.gov (United States)

    Zhang, Shengwei; Wang, Junping; Chen, Shaolong; Yin, Jiye; Pan, Zhiyuan; Liu, Keke; Li, Lin; Zheng, Yuling; Yuan, Yuan; Jiang, Yongqiang

    2016-01-01

    Blood platelets play important roles during pathological thrombocytopenia in streptococcal toxic shock syndrome (STSS). Streptococcus suis (S. suis) an emerging human pathogen, can cause STSS similarly to S. pyogenes. However, S. suis interactions with platelets are poorly understood. Here, we found that suilysin (SLY), different from other bacterial cholesterol-dependent cytolysins (CDCs), was the sole stimulus that induced platelet aggregation. Furthermore, the inside-out activation of GPIIb/IIIa of platelets mediated SLY-induced platelet aggregation. This process was triggered by Ca2+ influx that depend on the pore forming on platelets by SLY. Additionally, although SLY induced α-granule release occurred via the MLCK-dependent pathway, PLC-β-IP3/DAG-MLCK and Rho-ROCK-MLCK signaling were not involved in SLY-induced platelet aggregation. Interestingly, the pore dependent Ca2+ influx was also found to participate in the induction of platelet aggregation with pneumolysin (PLY) and streptolysin O (SLO), two other CDCs. It is possible that the CDC-mediated platelet aggregation we observed in S. suis is a similar response mechanism to that used by a wide range of bacteria. These findings might lead to the discovery of potential therapeutic targets for S. suis-associated STSS. PMID:27800304

  7. Mechanisms of xenogeneic baboon platelet aggregation and phagocytosis by porcine liver sinusoidal endothelial cells.

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    Qiang Peng

    Full Text Available BACKGROUND: Baboons receiving xenogeneic livers from wild type and transgenic pigs survive less than 10 days. One of the major issues is the early development of profound thrombocytopenia that results in fatal hemorrhage. Histological examination of xenotransplanted livers has shown baboon platelet activation, phagocytosis and sequestration within the sinusoids. In order to study the mechanisms of platelet consumption in liver xenotransplantation, we have developed an in vitro system to examine the interaction between pig endothelial cells with baboon platelets and to thereby identify molecular mechanisms and therapies. METHODS: Fresh pig hepatocytes, liver sinusoidal and aortic endothelial cells were isolated by collagenase digestion of livers and processing of aortae from GTKO and Gal+ MGH-miniature swine. These primary cell cultures were then tested for the differential ability to induce baboon or pig platelet aggregation. Phagocytosis was evaluated by direct observation of CFSE labeled-platelets, which are incubated with endothelial cells under confocal light microscopy. Aurintricarboxylic acid (GpIb antagonist blocking interactions with von Willebrand factor/vWF, eptifibatide (Gp IIb/IIIa antagonist, and anti-Mac-1 Ab (anti-α(Mβ(2 integrin Ab were tested for the ability to inhibit phagocytosis. RESULTS: None of the pig cells induced aggregation or phagocytosis of porcine platelets. However, pig hepatocytes, liver sinusoidal and aortic endothelial cells (GTKO and Gal+ all induced moderate aggregation of baboon platelets. Importantly, pig liver sinusoidal endothelial cells efficiently phagocytosed baboon platelets, while pig aortic endothelial cells and hepatocytes had minimal effects on platelet numbers. Anti-MAC-1 Ab, aurintricarboxylic acid or eptifibatide, significantly decreased baboon platelet phagocytosis by pig liver endothelial cells (P<0.01. CONCLUSIONS: Although pig hepatocytes and aortic endothelial cells directly caused

  8. Human platelet aggregation inhibitors from thyme (Thymus vulgaris L.).

    Science.gov (United States)

    Okazaki, Kenji; Kawazoe, Kazuyoshi; Takaishi, Yoshihisa

    2002-06-01

    Two antiaggregant compounds, thymol (compound 1) and 3,4,3',4'-tetrahydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl (compound 2) were isolated from the leaves of thyme (Thymus vulgaris L.). The structures were determined by (1)H-, (13)C-NMR and mass spectra (MS) studies. These compounds inhibited platelet aggregation induced by collagen, ADP, arachidonic acid (AA) and thrombin except that compound 2 did not inhibit platelet aggregation induced by thrombin.

  9. Reference intervals for platelet aggregation assessed by multiple electrode platelet aggregometry

    DEFF Research Database (Denmark)

    Rubak, Peter; Villadsen, Kirsten; Hvas, Anne-Mette

    2012-01-01

    Abstract Introduction Analyses of platelet aggregation in hirudin whole blood using Multiplate® was validated. Reference intervals for the most commonly used agonists were established, and the association between platelet aggregation, age, gender and haematological values was analysed. Material...... and methods We included 121 healthy individuals to establish reference intervals and six healthy individuals for evaluation of the day-to-day variation. Platelet aggregation was evaluated on hirudin whole blood employing Multiplate® induced by arachidonic acid, ADP, collagen and ristocetin (RISTOlow...... reference interval is presented as 95% confidence interval suitable for any age and both sex. Day-to-day variation was

  10. Adenosine diphosphate-induced aggregation of human platelets in flow through tubes. I. Measurement of concentration and size of single platelets and aggregates.

    Science.gov (United States)

    Bell, D N; Spain, S; Goldsmith, H L

    1989-11-01

    A double infusion flow system and particle sizing technique were developed to study the effect of time and shear rate on adenosine diphosphate-induced platelet aggregation in Poiseuille flow. Citrated platelet-rich plasma, PRP, and 2 microM ADP were simultaneously infused into a 40-microliters cylindrical mixing chamber at a fixed flow ratio, PRP/ADP = 9:1. After rapid mixing by a rotating magnetic stirbar, the platelet suspension flowed through 1.19 or 0.76 mm i.d. polyethylene tubing for mean transit times, t, from 0.1 to 86 s, over a range of mean tube shear rate, G, from 41.9 to 1,000 s-1. Known volumes of suspension were collected into 0.5% buffered glutaraldehyde, and all particles in the volume range 1-10(5) microns 3 were counted and sized using a model ZM particle counter (Coulter Electronics Inc., Hialeah, FL) and a logarithmic amplifier. The decrease in the single platelet concentration served as an overall index of aggregation. The decrease in the total particle concentration was used to calculate the collision capture efficiency during the early stages of aggregation, and aggregate growth was followed by changes in the volume fraction of particles of successively increasing size. Preliminary results demonstrate that both collision efficiency and particle volume fraction reveal important aspects of the aggregation process not indicated by changes in the single platelet concentration alone.

  11. In vitro model of platelet aggregation in stenotic arteries

    Energy Technology Data Exchange (ETDEWEB)

    Morley, D.; Santamore, W.P.

    1988-07-01

    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.

  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

    2015-01-01

    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. Influence of caffeine on blood pressure and platelet aggregation

    Directory of Open Access Journals (Sweden)

    José Wilson S. Cavalcante

    2000-08-01

    Full Text Available OBJECTIVE: Studies have demonstrated that methylxanthines, such as caffeine, are A1 and A2 adenosine receptor antagonists found in the brain, heart, lungs, peripheral vessels, and platelets. Considering the high consumption of products with caffeine in their composition, in Brazil and throughout the rest of the world, the authors proposed to observe the effects of this substance on blood pressure and platelet aggregation. METHODS: Thirteen young adults, ranging from 21 to 27 years of age, participated in this study. Each individual took 750mg/day of caffeine (250mg tid, over a period of seven days. The effects on blood pressure were analyzed through the pressor test with handgrip, and platelet aggregation was analyzed using adenosine diphosphate, collagen, and adrenaline. RESULTS: Diastolic pressure showed a significant increase 24 hours after the first intake (p<0.05. This effect, however, disappeared in the subsequent days. The platelet aggregation tests did not reveal statistically significant alterations, at any time during the study. CONCLUSION: The data suggest that caffeine increases diastolic blood pressure at the beginning of caffeine intake. This hypertensive effect disappears with chronic use. The absence of alterations in platelet aggregation indicates the need for larger randomized studies.

  14. Sustained increase in platelet aggregation after the cessation of clopidogrel.

    Science.gov (United States)

    Djukanovic, Nina; Todorovic, Zoran; Zamaklar-Trifunovic, Danijela; Protic, Dragana; Dzudovic, Boris; Ostojic, Miodrag; Obradovic, Slobodan

    2016-02-01

    This study shows that the abrupt cessation of one-year clopidogrel treatment was not associated with thrombotic events in a prospective, multicentre study that enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel 1 year after the stent placement. The aim of the study was to investigate the causes of a sustained increase of platelet aggregability, considering that the values of platelet aggregation stimulated with ADP + PGE1 (ADPHS values) significantly increased 10-90 days after the cessation of clopidogrel. Values of platelet aggregation induced by thrombin receptor activating peptide (TRAP values) and arachidonic acid (ASPI values) were divided into quartiles on the basis of ADPHS values 10 days after stopping clopidogrel (ADPHS10 ). There was a significant difference between TRAP values divided into quartiles according to ADPHS10 , 10, 45 and 90 days after stopping clopidogrel (P clopidogrel (P = 0.028 and 0.003). The results of the study indicate that patients with early pronounced rebound phenomena to clopidogrel termination have a long-term (at least 90 days) increased platelet aggregation to other agonists such as thrombin-related activated protein and arachidonic acid, suggesting the complex mutual relationship of various factors/agonists influencing the function of platelets.

  15. A new ibuprofen derivative inhibits platelet aggregation and ROS mediated platelet apoptosis.

    Directory of Open Access Journals (Sweden)

    Kodagahalli S Rakesh

    Full Text Available Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease, cardiovascular diseases (CVDs and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+ levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.

  16. Spontaneous platelet aggregation in patients with acute coronary syndrome.

    Science.gov (United States)

    Mazurov, A V; Khaspekova, S G; Yakushkin, V V; Khachikyan, M V; Zyuryaev, I T; Ruda, M Ya

    2013-05-01

    Spontaneous platelet aggregation was evaluated in patients with acute coronary syndrome on days 1, 3-5, and 8-12 of the disease. On day 1, aggregation was analyzed after aspirin, but before clopidogrel administration; during other periods after both antiaggregants. The mean levels of spontaneous aggregation after antithrombotic therapy did not change during different periods after the onset of acute coronary syndrome, in contrast to ADP-induced aggregation that decreased after the development of clopidogrel effects (days 3-5 and 8-12). Spontaneous aggregation during different periods directly correlated (r>0.4, p<0.01) with spontaneous and ADP-induced aggregation during different periods (r=0.372, r=0.447, and r=0.543 on days 1, 3-5, and 8-12, respectively; p<0.01). No relationship between spontaneous aggregation and plasma concentration of von Willebrand's factor was detected. Spontaneous aggregation was completely suppressed after in vitro addition of prostaglandin E1 (platelet activation inhibitor), slightly (by ≈20%) decreased in the presence of antibodies to glycoprotein Ib, blocking its reactions with von Willebrand's factor, and did not change in the presence of aptamer inhibiting thrombin activity.

  17. ENHANCED PLATELET AGGREGABILITY UNDER HIGH SHEAR STRESS IN CORONARY CIRCULATION OF PATIENTS WITH UNSTABLE ANGINA

    OpenAIRE

    Doi, Naofumi

    2000-01-01

    Mechanical forces, including high shear stress, have been found to cause platelet aggregation. Although increased platelet aggregation is also associated with the pathophysiology of unstable angina, it is not known whether platelet aggregation induced by high shear stress occurs in the coronary circulation of patients with unstable angina. We assayed high shear stress induced platelet aggregation (h-SIPA) in each of 25 patients with unstable angina and a severe stenotic lesion of the left cor...

  18. Inhibitory effect of GBH on platelet aggregation through inhibition of intracellular Ca2+ mobilization in activated human platelets.

    Science.gov (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

    2004-11-05

    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.

  19. Effects of argon laser on in vitro aggregation of platelets in platelet rich plasma and whole blood

    Energy Technology Data Exchange (ETDEWEB)

    Doerger, P.T.; Glueck, H.I.; McGill, M.

    1988-06-01

    The effects of an Argon laser on platelet aggregation were studied, since platelets may be exposed to laser energy when used intravascularly. Various preparations of platelets in platelet rich plasma (PRP) and whole blood, with or without aspirin, were tested with the aggregating agents ADP, collagen, thrombin, and epinephrine. Simultaneous release of ATP was also measured in PRP. At relatively low levels of irradiation, platelet aggregation was potentiated. Enhancement was evidenced by an increase in percent aggregation, earlier onset of the reaction, and reduction in the amount of aggregating agent required. In PRP, the mechanism of laser potentiation appeared to be the release of endogenous ATP from platelets. At relatively high levels of irradiation, platelets were destroyed and aggregation abolished. In whole blood, the mechanism was somewhat more complicated since release of ATP occurred from RBCs as well as platelets. Spontaneous aggregation following laser treatment occurred in isolated instances in PRP and in every trial in whole blood preparations. Aspirin ingestion inhibited the laser's effects in PRP but not in whole blood. These results may have important clinical implications for laser angioplasty, and the potentiated aggregation response may prove useful in laboratory studies of platelet function.

  20. Reduced platelet hyperreactivity and platelet-monocyte aggregation in HIV-infected individuals receiving a raltegravir-based regimen

    NARCIS (Netherlands)

    Tunjungputri, R.N.; Ven, A.J. van der; Schonsberg, A.; Mathan, T.S.M.; Koopmans, P.P.; Roest, M.; Fijnheer, R.; Groot, P.G. de; Mast, Q. de

    2014-01-01

    OBJECTIVE: Platelets are key cells in atherosclerosis and acute cardiovascular events. Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in HIV-infected patients and may contribute to the excess cardiovascular risk. The integrase inhibitor raltegravir (RAL) has bee

  1. Spontaneous and Induced Platelet Aggregation during Pregnancy and Labor

    Directory of Open Access Journals (Sweden)

    T. P. Bondar

    2016-01-01

    Full Text Available Objective: to evaluate changes in characteristics of spontaneous platelet (Pt aggregation in patients with obstetric complications associated with hereditary thrombophilia.Materials and methods. Blood samples were taken from 52 recently confined women on the first day after labor; at that, ethic regulations for the preanalytical phase were followed. Determination of PlA1/ PlA2 polymorphism enotype was performed by means of amplificationrestriction analysis. Geometrical characteristics of patients' peripheral blood Pt aggregation were studied by means of AFM Integra Prima. The degree of confidence of the parameters under test was determined using the ttest, and the significance level was considered valid at P<0.05.Results. A statistical analysis of the findings demonstrated that the length of Pt aggregates in healthy pregnant women was significantly higher than that in healthy nonpregnant women at all study phases. Patients with the P1A1/P1A2 polymorphism in the GP IIb/IIIa Pt receptor gene demonstrated increased widthm height, and density of Pt aggregates. The changes were most significant during the incubation phase lasting for 15 and 30 minutes. The study of geometric parameters of different exposures demonstrated the following: the longer the incubation period, the greater the difference between geometric parameters of the aggregates (e.g. height, length, and width. Conclusion. The analysis of obtained data demonstrated that the presence of P1A1/P1A2 polymorphism in GP IIb/IIIa Pt gene receptor contributes to the decrease in the platelet response threshold and enhances the spontaneous Pt aggregation. The imaging of aggregates provides strong evidence for the accelerated growth of the aggregates in thrombotic complications of pregnancy.

  2. Metabolic energy is required in human platelets at any stage during optical aggregation and secretion

    NARCIS (Netherlands)

    Akkerman, Jan Willem N.; Verhoeven, A.J.M.; Mommersteeg, M.E.

    1984-01-01

    The relationship between metabolic energy and platelet aggregation and secretion was investigated by sudden exhaustion of the cell energy content after these platelet responses had been initiated. In normal platelets, optical aggregation was at any stage susceptible to energy exhaustion, whereas sin

  3. 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.

    1986-03-01

    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 ..mu..M) was not affected by ethanol, at concentrations up to 5 mg/ml (lethal). Primary ADP-induced (5 ..mu..M) 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 ..mu..M) 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 ..mu.. 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.

  4. Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Nielsen, Christian; Söderström, Anna Cecilia

    2017-01-01

    Dabigatran is an oral anticoagulant and a reversible inhibitor of thrombin. Further, dabigatran might affect platelet function through a direct effect on platelet thrombin receptors. The aim was to investigate the effect of dabigatran on platelet activation and platelet aggregation. Healthy donor...

  5. Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

    Science.gov (United States)

    Corbalan, J Jose; Medina, Carlos; Jacoby, Adam; Malinski, Tadeusz; Radomski, Marek W

    2012-01-01

    Background Amorphous silica nanoparticles (SiNP) can be used in medical technologies and other industries leading to human exposure. However, an increased number of studies indicate that this exposure may result in cardiovascular inflammation and damage. A high ratio of nitric oxide to peroxynitrite concentrations ([NO]/[ONOO−]) is crucial for cardiovascular homeostasis and platelet hemostasis. Therefore, we studied the influence of SiNP on the platelet [NO]/[ONOO−] balance and platelet aggregation. Methods Nanoparticle–platelet interaction was examined using transmission electron microscopy. Electrochemical nanosensors were used to measure the levels of NO and ONOO− released by platelets upon nanoparticle stimulation. Platelet aggregation was studied using light aggregometry, flow cytometry, and phase contrast microscopy. Results Amorphous SiNP induced NO release from platelets followed by a massive stimulation of ONOO− leading to an unfavorably low [NO]/[ONOO−] ratio. In addition, SiNP induced an upregulation of selectin P expression and glycoprotein IIb/IIIa activation on the platelet surface membrane, and led to platelet aggregation via adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all the effects on platelet aggregation were inversely proportional to nanoparticle size. Conclusions The exposure of platelets to amorphous SiNP induces a critically low [NO]/[ONOO−] ratio leading to platelet aggregation. These findings provide new insights into the pharmacological profile of SiNP in platelets. PMID:22334785

  6. [Effect of magnesium, acetylsalicilic acid and emoxypine on aggregation of platelets].

    Science.gov (United States)

    Loznikova, S Zh; Sukhodola, A A; Shcharbina, N Iu; Shcharbin, D G

    2014-01-01

    The thrombin-induced platelet aggregation was studied in the absence and presence of magnesium sulfate, acetylsalicylic acid and emoxypine. It was found that all the preparations studied were able separately to decrease platelet aggregation. In contrast, their joint action was not able to affect the aggregation of platelets. The data obtained can be used to choose the treatment strategy for patients with ischemic stroke.

  7. Effect of coffee drinking on platelets: inhibition of aggregation and phenols incorporation.

    Science.gov (United States)

    Natella, F; Nardini, M; Belelli, F; Pignatelli, P; Di Santo, S; Ghiselli, A; Violi, F; Scaccini, C

    2008-12-01

    Epidemiological studies indicate a J-shaped relationship linking coffee consumption and cardiovascular risk, suggesting that moderate coffee consumption can be beneficial. Platelet aggregation is of critical importance in thrombotic events, and platelets play a major role in the aetiology of several CVD. The aim of this study was to evaluate the effect of coffee drinking on platelet aggregation ex vivo, using caffeine as control. A crossover study was performed on ten healthy subjects. In two different sessions, subjects drank 200 ml coffee, containing 180 mg caffeine, or a capsule of caffeine (180 mg) with 200 ml water. Platelets were separated from plasma at baseline and 30 and 60 min after coffee drinking. Platelet aggregation was induced with three different agonists: collagen, arachidonic acid and ADP. Coffee drinking inhibited collagen (P Caffeine intake did not affect platelet aggregation induced by the three agonists. Coffee consumption induced a significant increase of platelet phenolic acids (likely present as glucuronate and sulphate derivatives), caffeic acid, the principal phenolic acid in coffee, raising from 0.3 (SEM 0.1) to 2.4 (SEM 0.6) ng/mg (P Caffeine was not detectable in platelets. Coffee drinking decreases platelet aggregation, and induces a significant increase in phenolic acid platelet concentration. The antiplatelet effect of coffee is independent from caffeine and could be a result of the interaction of coffee phenolic acids with the intracellular signalling network leading to platelet aggregation.

  8. PPARγ ligands decrease hydrostatic pressure-induced platelet aggregation and proinflammatory activity.

    Directory of Open Access Journals (Sweden)

    Fang Rao

    Full Text Available Hypertension is known to be associated with platelet overactivity, but the direct effects of hydrostatic pressure on platelet function remain unclear. The present study sought to investigate whether elevated hydrostatic pressure is responsible for platelet activation and to address the potential role of peroxisome proliferator-activated receptor-γ (PPARγ. We observed that hypertensive patients had significantly higher platelet volume and rate of ADP-induced platelets aggregation compared to the controls. In vitro, Primary human platelets were cultured under standard (0 mmHg or increased (120, 180, 240 mmHg hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with morphological changes in platelets. Platelet aggregation and PAC-1 (the active confirmation of GPIIb/IIIa binding were increased, CD40L was translocated from cytoplasm to the surface of platelet and soluble CD40L (sCD40L was released into the medium in response to elevated hydrostatic pressure (180 and 240 mmHg. The PPARγ activity was up-regulated as the pressure was increased from 120 mmHg to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and translocation and release of CD40L were all attenuated by the PPARγ agonist Thiazolidinediones (TZDs. These results demonstrate that platelet activation and aggregation are increased by exposure to elevated pressure and that PPARγ may modulate platelet activation induced by high hydrostatic pressure.

  9. Mediterranean wild plants reduce postprandial platelet aggregation in patients with metabolic syndrome.

    Science.gov (United States)

    Fragopoulou, Elizabeth; Detopoulou, Paraskevi; Nomikos, Tzortzis; Pliakis, Emmanuel; Panagiotakos, Demosthenes B; Antonopoulou, Smaragdi

    2012-03-01

    Postprandial platelet hyperactivity and aggregation play a crucial role in the pathogenesis of metabolic syndrome. The purpose of the present study was to evaluate the effect of boiled wild plants consumption on the postprandial platelet aggregation in metabolic syndrome patients. Patients consumed 5 meals in a random order (ie, 4 wild plant meals, namely, Reichardia picroides [RP], Cynara cardunculus, Urospermum picroides [UP], and Chrysanthemum coronarium, and a control meal, which contained no wild plants). Several biochemical indices as well as platelet activating factor (PAF)- and adenosine diphosphate-induced ex vivo platelet aggregation were measured postprandially. Moreover, the ability of plants extract to inhibit rabbit platelet aggregation was tested in vitro. The consumption of RP and UP meals significantly reduced ex vivo adenosine diphosphate-induced postprandial platelet aggregation compared with the control meal. The consumption of UP meals significantly reduced the ex vivo PAF-induced platelet aggregation postprandially. Both UP and RP extracts significantly inhibited PAF-induced rabbit platelet aggregation in vitro. Wild plants consumption reduced postprandial platelet hyperaggregability of metabolic syndrome patients, which may account for their healthy effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Inhibiting platelets aggregation could aggravate the acute infection caused by Staphylococcus aureus.

    Science.gov (United States)

    Zhang, Xin; Liu, Yu; Gao, Yaping; Dong, Jie; Mu, Chunhua; Lu, Qiang; Shao, Ningsheng; Yang, Guang

    2011-01-01

    Several fibrinogen binding proteins (Fibs) play important roles in the pathogenesis of Staphylococcus aureus (S. aureus). Most Fibs can promote the aggregation of platelets during infection, but the extracellular fibrinogen-binding protein (Efb) is an exception. It is reported that Efb can specifically bind fibrinogen and inhibit the aggregation of platelet with its N terminal. However, the biological significance of platelet aggregation inhibition in the infection caused by S. aureus is unclear until now. Here, we demonstrated that the persistence and aggregation of platelets were important for killing S. aureus in whole blood. It was found that the N terminal of Efb (EfbN) and platelets inhibitors could increase the survival of S. aureus in whole blood. The study in vivo also showed that EfbN and platelets inhibitors could reduce the killing of S. aureus and increase the lethality rate of S. aureus in the acute infection mouse model.

  11. A practical synthesis of sarpogrelate hydrochloride and in vitro platelet aggregation inhibitory activities of its analogues

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A convenient approach for the preparation of sarpogrelate hydrochloride was developed.Two series of sarpogrelate hydrochloride analogues were designed and synthesized in order to improve their platelet aggregation inhibitory activities, biological tests suggested that these compounds have platelet aggregation inhibitory activities to some extent.

  12. In vitro effects of mercury on platelet aggregation, thromboxane and vascular prostacyclin production.

    Science.gov (United States)

    Caprino, L; Togna, A R; Cebo, B; Dolci, N; Togna, G

    1983-01-01

    Mercuric chloride [25-50 micrograms/ml platelet-rich plasma (PRP)] lowers the threshold concentration of arachidonic acid (AA) required for triggering rabbit platelet aggregation and causes a marked increase of thromboxane production. The metal, added as HgCl2, does not modify (50 micrograms/ml PRP) or block (100 micrograms/ml PRP) the platelet aggregation wave induced by a normal aggregating dose of AA. Whether or not AA-induced platelet aggregation takes place, a large increase in thromboxane production is observed. Methyl mercury, assayed as reference drug, induces platelet aggregation and a significant increase of thromboxane levels. Finally, HgCl2 and methyl mercury, in a concentration range of 0.125-0.5 micrograms/microliters in the incubation liquid, induce an increased prostacyclin release from rat aortic tissue.

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

    OpenAIRE

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

    2014-01-01

    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 ...

  14. Parsley extract inhibits in vitro and ex vivo platelet aggregation and prolongs bleeding time in rats.

    Science.gov (United States)

    Gadi, Dounia; Bnouham, Mohamed; Aziz, Mohammed; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Legrand, Chantal; Lafeve, Françoise Fauvel; Mekhfi, Hassane

    2009-08-17

    Many cardiovascular diseases are associated with an increase in blood platelet activity. In Morocco, parsley (Petroselinum crispum, Apiaceae) is one of the medicinal herbs used to treat cardiovascular diseases such as arterial hypertension. In this study, crude aqueous extract (CAE) of parsley was evaluated for its anti-platelet activity in experimental animals on platelet aggregation in vitro and ex vivo; and on bleeding time in vivo. The in vitro aggregation was monitored after pre-incubation of platelets with CAE. The bleeding time and ex vivo aggregation were performed after oral treatment. CAE inhibited dose dependently platelet aggregation in vitro induced by thrombin, ADP, collagen and epinephrine. The oral administration of CAE (3g/kg) inhibited significantly (p<0.001) platelet aggregation ex vivo and prolonged bleeding time (p<0.001) without changes in the platelet amount. The prolongation of bleeding time by CAE may be attributed to the observed inhibition of platelet aggregation. These effects could be related in part to the polyphenolic compounds present in the extract. These results support the hypothesis that the dietary intake of parsley may be benefit in the normalization of platelet hyperactivation, in the nutritional prevention of cardiovascular diseases and are potentially interesting in the development of new prevention strategies.

  15. COX, LOX and platelet aggregation inhibitory properties of Lauraceae neolignans.

    Science.gov (United States)

    Coy, Ericsson David; Cuca, Luis Enrique; Sefkow, Michael

    2009-12-15

    The anti-inflammatory potential of 26 neolignans (14 of the bicyclooctane-type and 12 of the benzofuran-type), isolated from three Lauraceae species (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), was evaluated in vitro through inhibition of COX-1, COX-2, 5-LOX and agonist-induced aggregation of rabbit platelets. Benzofuran neolignans were found to be selective COX-2 inhibitors, whereas bicyclooctane neolignans inhibit selectively the PAF-action as well as COX-1 and 5-LOX. The neolignan 9-nor-7,8-dehydro-isolicarin B 15 and cinerin C 7 were found to be the most potent COX-2 inhibitor and PAF-antagonist, respectively. Nectamazin C 10 exhibited dual 5-LOX/COX-2 inhibition.

  16. [Effect of dauricine on rat and human platelet aggregation and metabolism of arachidonic acid in washed rat platelets].

    Science.gov (United States)

    Tong, L; Yue, T L

    1989-01-01

    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.

  17. Platelet aggregation promoted by biofilms of oral bacteria and the effect of mouth rinses in vitro.

    Science.gov (United States)

    Tu, Yan; Chen, Yadong; Zheng, Chongyang; Chen, Hui

    2016-08-02

    The purpose of this study was to observe platelet aggregation promoted by biofilms of Streptococcus sanguinis and Porphyromonas gingivalis and to evaluate the effect of two different mouth rinses on this process. In the first experiment, the same amount of S. sanguinis, P. gingivalis, and the S. sanguinis + P. gingivalis mixed solution was added to an equivalent amount of platelet-rich plasma (PRP). Aggregation was measured using a recording platelet aggregometer. In the second experiment, S. sanguinis, P. gingivalis, S sanguinis + P. gingivalis mixed solutions were pretreated with either Listerine antiseptic mouth rinse or Xipayi mouth rinse for 3 minutes, 6 minutes, and 10 minutes, respectively. The same amount of solution was added to the PRP, and the inhibition of aggregation was measured. In the first experiment, S. sanguinis and P. gingivalis were able to induce platelet aggregation. The aggregation rate of S. sanguinis + P. gingivalis was significantly lower than that of either S. sanguinis or P. gingivalis. In the second experiment, when S. sanguinis, P. gingivalis, and the S. sanguinis + P. gingivalis mixed solutions were pretreated with Listerine antiseptic mouth rinse for 3 minutes and Xipayi mouth rinse for 10 minutes, there was no significant platelet aggregation. Platelets could adhere to S. sanguinis or P. gingivalis, but when S. sanguinis was mixed with P. gingivalis, the aggregation rate was reduced significantly. Treatment with Listerine antiseptic mouth rinse or Xipayi mouth rinse inhibited the ability of the bacteria to induce platelet aggregation.

  18. Decreased platelet aggregation by shear stress-stimulated endothelial cells in vitro: description of a method and first results in diabetes.

    Science.gov (United States)

    De Franceschi, Maria S; Palange, Anna L; Mancuso, Anna; Grande, Laura; Muccari, Domenico; Scavelli, Faustina B; Irace, Concetta; Gnasso, Agostino; Carallo, Claudio

    2015-01-01

    The interaction between platelets and endothelium in vivo is a complex phenomenon. Our aim was to develop an in vitro system that mimics the in vivo environment and investigate platelet function in a common pathological condition. Human umbilical vein endothelial cells were used and platelets from 28 type 2 diabetes patients were studied under shear stress conditions. Mean coefficient of variation of platelet aggregation was 10% in dynamic conditions in the presence of endothelium. Endothelial cells increased the concentration of inductor needed to achieve 50% platelet aggregation to adenosine diphosphate from 2.6 ± 1.3 in static conditions to 3.7 ± 1.3 µM in dynamic conditions. A similar pattern was observed when collagen was used for platelet activation. Incubation of endothelium with a nitric oxide inhibitor abolished this effect, indicating platelet inhibitory effect of endothelial cells is nitric oxide mediated. Platelet reactivity of healthy controls was less influenced by the presence of endothelial cells and displayed reduced basal platelet reactivity compared with platelets from diabetes patients. We show that platelet aggregation in diabetes as commonly reported in vitro may not fully reflect the in vivo pathophysiological process. Future studies are warranted to investigate other pathological conditions and analyse the effects of antiplatelet agents using this system.

  19. Comparative Effects of Phenylbutazone, Naproxen and Flunixin Meglumine on Equine Platelet Aggregation and Platelet Factor 3 Availability in vitro

    Science.gov (United States)

    Johnstone, I.B.

    1983-01-01

    Nonsteroidal anti-inflammatory drugs are commonly used in the treatment of inflammatory conditions, and have potential value in the treatment of thrombotic disease in the horse. This study compares the potency of three nonsteroidal anti-inflammatory drugs phenylbutazone, naproxen (equiproxen) and flunixin meglumine (banamine) with respect to their effects on equine platelets. Two functional responses of horse platelets were evaluated in vitro: their ability to aggregate and their ability to make available platelet factor 3 procoagulant activity. Flunixin at a concentration of 10-6 M significantly depressed the maximum degree of adenosine diphosphate-induced (10-6M) aggregation while much higher concentrations of phenylbutazone and naproxen (5 X 105M) were required to produce similar effects. None of the non-steriodal anti-inflammatory drugs significantly affected the duration of the lag phase or the initial velocity of adenosine diphosphate-induced aggregation within the range of drug concentrations used (10-6-10-3M). The lag phase and initial velocity of acid-soluble collagen-induced aggregation were significantly affected by 10-6 M flunixin and 10-4 M phenylbutazone or naproxen was required to produce equivalent effects. Concentrations of 5 X 10-6 M flunixin and 5 X 10-4 M phenylbutazone or naproxen were required to significantly depress the degree of collaen-induced aggregation of horse platelets. Although the effects of the nonsteroidal anti-inflammatory drugs were qualitatively similar, flunixin was a much more potent inhibitor of platelet aggregation than either of the other two drugs (which were equipotent). At very high drug concentrations (5 X 10-4 M and greater), all three drugs produced the same degree of inhibition of equine platelet aggregation. Platelet factor 3 activity was made available by exposing horse platelets to 10-5 M adenosine diphosphate or 1:800 acid-soluble collagen; but not by exposure to a suspension of kaolin particles. Only a small

  20. EFFECTS OF CARVEDILOL ON PLATELET AGGREGATION IN MEN WITH ST-ELEVATION ACUTE MYOCARDIAL INFARCTION

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    A. N. Zakirova

    2010-01-01

    Full Text Available Aim. To study influence of beta-blockers carvedilol and metoprolol tartrate on platelet aggregative ability, evaluated by three different methods, in patients with acute ST segment elevation myocardial infarction (STEMI.Material and methods. A total of 86 men aged 36-68 with uncomplicated STEMI were included into an open, comparative, randomized study. Patients were randomized into two groups of beta-blocker treatments. Patients (n=44 of the first group received carvedilol; patients (n=42 of the second one - metoprolol tartrate. Parameters of platelet hemostasis: the maximum amplitude and rate of platelet aggregation induced by ADP, ristomycin and collagen; mean platelet volume (MPV; serum level of soluble CD40 ligand (sCD40L were evaluated on the 2nd and 24th day after STEMI onset.Results. In patients with uncomplicated STEMI carvedilol more prominently reduced in vitro platelet aggregation induced by adenozin-5'-diphosphate in high concentration, ristomycin and collagen than metoprolol tartrate. Сarvedilol also more significantly decreased MPV in comparison with metoprolol tartrate. However, effect of both carvedilol and metoprolol tartrate on the level of another platelet aggregation marker - sCD40L was comparable.Conclusion. Carvedilol and metoprolol tartrate have similar effect on platelet aggregation though in according to some tests carvedilol more prominently reduces platelet aggregation than metoprolol tartrate.

  1. Platelet aggregation measurement for assessment of hemostasis failure mechanisms in patients with gastroduodenal ulcer bleeding

    Science.gov (United States)

    Barinov, Edward; Sulaieva, Oksana; Lyakch, Yuriy; Guryanov, Vitaliy; Kondratenko, Petr; Radenko, Yevgeniy

    2013-01-01

    Background The purpose of this study was to identify factors associated with the risk of unsustainable hemostasis in patients with gastric and duodenal ulcer bleeding by in vitro assessment of platelet reactivity using artificial neural networks. Methods Patients with gastroduodenal ulcers complicated by bleeding were studied. Platelet aggregation was measured using aggregometry with adenosine diphosphate 5 μM, epinephrine 2.5 μM, 5-hydroxytryptophan 10 μM, collagen 1 μM, and thrombin 0.06 NIH Unit/mL as agonists. Multiple logistic regression was used to evaluate the independent relationship between demographic, clinical, endoscopic, and laboratory data and in vitro assessment of platelet reactivity and local parameters of hemostasis in patients with ulcer bleeding. Results Analysis of platelet aggregation in patients with gastroduodenal ulcer bleeding allowed the variability of platelet response to different agonists used in effective concentration which induces 50% platelet aggregation (EC50) to be established. The relationship between platelet aggregation and the spatial-temporal characteristics of ulcers complicated by bleeding was demonstrated. Adrenoreactivity of platelets was associated with time elapsed since the start of ulcer bleeding and degree of hemorrhage. The lowest platelet response to collagen and thrombin was detected in patients with active bleeding (P < 0.001) and unsustainable recent bleeding (P < 0.01). Decreased adenosine diphosphate-induced platelet aggregation in patients with ulcer bleeding was correlated with the platelet response to thrombin (r = 0.714, P < 0.001) and collagen (r = 0.584, P < 0.01). Conclusion Estimation of platelet reactivity in vitro indicates the key mechanisms of failure of hemostasis in patients with ulcer bleeding. In addition to gender, an important determinant of unsustainable hemostasis was a decreased platelet response to thrombin and adenosine diphosphate. PMID:23950655

  2. Platelets as Central Mediators of Systemic Inflammatory Responses

    OpenAIRE

    Smith, Tammy L; Weyrich, Andrew S.

    2010-01-01

    Systemic inflammatory responses are associated with high morbidity and mortality and represent a diverse and clinically challenging group of diseases. Platelets are increasingly linked to inflammation, in addition to their well-known roles in hemostasis and thrombosis. There is agreement that traditional functions of platelets, including adherence, aggregation, and secretion of preformed mediators, contribute to systemic inflammatory responses. However, emerging evidence indicates that platel...

  3. Characterization of the platelet-aggregating activity of cancer cells with different metastatic potential.

    Science.gov (United States)

    Grignani, G; Pacchiarini, L; Almasio, P; Pagliarino, M; Gamba, G; Rizzo, S C; Ascari, E

    1986-08-15

    We studied the mechanisms of platelet activation by sublines exhibiting different metastatic potential of two murine experimental tumors: sublines M4 and M9 of the benzopyrene-induced mFS6 sarcoma and sublines B77-AA6 and B77-3T3 of RSV-transformed BALB/c 3T3 fibroblasts. The neoplastic cells of both models induced platelet aggregation, secretion and prostaglandin biosynthesis. In the first model but not in the second, all these processes correlated with the in vivo malignancy of cells. Pretreatment of B77-AA6 and B77-3T3 cells with apyrase significantly decreased platelet aggregation, while pretreatment of M4 cells was ineffective. However, pretreatment with trypsin or neuraminidase was effective in reducing platelet aggregation induced by M4 cells, but not that induced by any of the others; furthermore, phospholipase A2 reduced the platelet response by all sublines. Finally, platelet-activating activity was also found in the pellets obtained following centrifugation of culture media. These results suggest that platelets are stimulated by cancer cells through different mechanisms; platelet activation by a sialo-lipo-protein complex of the cellular membrane was found to be characteristic of the model in which the platelet-aggregating activity of neoplastic cells correlated with their in vivo metastatic behavior.

  4. Platelets protect lung from injury induced by systemic inflammatory response

    Science.gov (United States)

    Luo, Shuhua; Wang, Yabo; An, Qi; Chen, Hao; Zhao, Junfei; Zhang, Jie; Meng, Wentong; Du, Lei

    2017-01-01

    Systemic inflammatory responses can severely injure lungs, prompting efforts to explore how to attenuate such injury. Here we explored whether platelets can help attenuate lung injury in mice resulting from extracorporeal circulation (ECC)-induced systemic inflammatory responses. Mice were subjected to ECC for 30 min, then treated with phosphate-buffered saline, platelets, the GPIIb/IIIa inhibitor Tirofiban, or the combination of platelets and Tirofiban. Blood and lung tissues were harvested 60 min later, and lung injury and inflammatory status were assessed. As expected, ECC caused systemic inflammation and pulmonary dysfunction, and platelet transfusion resulted in significantly milder lung injury and higher lung function. It also led to greater numbers of circulating platelet-leukocyte aggregates and greater platelet accumulation in the lung. Platelet transfusion was associated with higher production of transforming growth factor-β and as well as lower levels of tumour necrosis factor-α and neutrophil elastase in plasma and lung. None of these platelet effects was observed in the presence of Tirofiban. Our results suggest that, at least under certain conditions, platelets can protect lung from injury induced by systemic inflammatory responses. PMID:28155889

  5. A critical role for the regulation of Syk from agglutination to aggregation in human platelets.

    Science.gov (United States)

    Shih, Chun-Ho; Chiang, Tin-Bin; Wang, Wen-Jeng

    2014-01-10

    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

  6. Myeloperoxidase modulates human platelet aggregation via actin cytoskeleton reorganization and store-operated calcium entry

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    Irina V. Gorudko

    2013-07-01

    Myeloperoxidase (MPO is a heme-containing enzyme released from activated leukocytes into the extracellular space during inflammation. Its main function is the production of hypohalous acids that are potent oxidants. MPO can also modulate cell signaling and inflammatory responses independently of its enzymatic activity. Because MPO is regarded as an important risk factor for cardiovascular diseases associated with increased platelet activity, we studied the effects of MPO on human platelet functional properties. Laser scanning confocal microscopy was used to reveal carbohydrate-independent MPO binding to human platelet membrane. Adding MPO to platelets did not activate their aggregation under basal conditions (without agonist. In contrast, MPO augmented agonist-induced platelet aggregation, which was not prevented by MPO enzymatic activity inhibitors. It was found that exposure of platelets to MPO leads to actin cytoskeleton reorganization and an increase in their elasticity. Furthermore, MPO evoked a rise in cytosolic Ca2+ through enhancement of store-operated Ca2+ entry (SOCE. Together, these findings indicate that MPO is not a direct agonist but rather a mediator that binds to human platelets, induces actin cytoskeleton reorganization and affects the mechanical stiffness of human platelets, resulting in potentiating SOCE and agonist-induced human platelet aggregation. Therefore, an increased activity of platelets in vascular disease can, at least partly, be provided by MPO elevated concentrations.

  7. In vitro platelet activation, aggregation and platelet-granulocyte complex formation induced by surface modified single-walled carbon nanotubes.

    Science.gov (United States)

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

    2015-08-01

    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.

  8. Echicetin coated polystyrene beads: a novel tool to investigate GPIb-specific platelet activation and aggregation.

    Science.gov (United States)

    Navdaev, Alexey; Subramanian, Hariharan; Petunin, Alexey; Clemetson, Kenneth J; Gambaryan, Stepan; Walter, Ulrich

    2014-01-01

    von Willebrand factor/ristocetin (vWF/R) induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways.

  9. Platelet aggregation responses vary over a period of time in healthy controls.

    Science.gov (United States)

    Refaai, Majed A; Frenkel, Eugene; Sarode, Ravi

    2010-01-01

    Platelet aggregation study is performed to investigate platelet function abnormality. A normal healthy control sample is usually run with the patient sample as a quality control measure. At our institution, we observed variations in platelet aggregation responses in our normal repeat controls. Therefore, we analysed aggregation parameters in these controls. Whole blood aggregation studies were performed with adenosine diphosphate (ADP), arachidonic acid (AA), collagen and ristocetin. Adenosine triphosphate (ATP) secretion was also measured simultaneously by leuciferin-leuciferase reaction. During a 5-year period, a total of 86 studies were performed on seven controls. Aggregations were within the acceptable range in 67% of the time. Collagen was the most affected agonist in our study. On five occasions, four controls had subnormal aggregations with two agonists. All abnormal responses were hypoaggregation except for two who had hyperaggregation with collagen and AA. Only one out of seven controls was always normal. In the presence of a subnormal control result, a new control was run before releasing the patient's platelet aggregation results. These findings suggest that many physiological factors, other than medications, may affect platelet function even in normal individuals. Therefore, a repeat study at a later date to demonstrate a reproducible abnormality would be prudent before labeling a patient's platelets abnormal.

  10. Effect of coffee extracts on plasma fibrinolysis and platelet aggregation.

    Science.gov (United States)

    Naito, Sawa; Yatagai, Chieko; Maruyama, Masugi; Sumi, Hiroyuki

    2011-04-01

    We have previously reported on study results showing that certain types of coffee have the activity to enhance fibrinolysis. This report covers the activity of 10 types of hot water extracts of coffee on human tissue-type plasminogen activator producing cells. Particularly strong activity (29-35 times the control amount) was observed for Blue Mountain, Yunnan and Kilimanjaro beans. It was found that the hot water extracts have anti-thrombin activity, and that coffee components have anti-platelet aggregation activity, although weak. It was revealed that there is no activity affecting tissue-type plasminogen activator producing cells in the coffee components chlorogenic acid, caffeine, quinic acid, trigonelline hydrochloride, 5-(hydroxymethyl)-2-furfuryl and caffeic acid. It was also revealed that there is activity in fractions with a molecular weight of 10,000 or less. This could also be inferred from the fact that oral administration of such fractions of coffee to human subjects resulted in a shortening of their plasma ELT (p<0.05).

  11. The effect of different strains of Helicobacter pylori on platelet aggregation

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    Paul A Corcoran

    2007-01-01

    Full Text Available BACKGROUND AND AIMS: Helicobacter pylori is the major causative agent in peptic ulcer disease and is strongly implicated in the development of gastric cancer. It has also been linked, less strongly, to cardiovascular disease. The mechanisms by which certain strains of H pylori induce platelet aggregation through interactions with platelet glycoprotein Ib have been previously described.

  12. The inhibitory activity of ginsenoside Rp4 in adenosine diphosphate-induced platelet aggregation

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    Young-Min Son

    2017-01-01

    Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.

  13. [Studies of platelet aggregation in six cases of EDTA-dependent pseudothrombocytopenia].

    Science.gov (United States)

    Shimasaki, A; Kato, T; Ozaki, Y

    1994-06-01

    Peripheral blood count was performed by a Coulter Model S Plus STKR on six pseudothrombocytopenia patients (age: 16-70, 2 men and 4 women) using three different anticoagulants. Treatment with ethylene diamine tetraacetate (EDTA, 1 mg/ml) or sodium heparin (25 U/ml) aggregated platelets, but sodium citrate (3.8%, 1:9) had no effect. Smear examination revealed much platelet clumping but the satellite phenomenon was not present. No specific pattern was elucidated concerning cell size distribution curves between treatment by EDTA and heparin. Theophylline (10 mg/ml) and prostaglandin I2 (1 microM) inhibited EDTA-induced platelet aggregation but aspirin (1.8 mM) did not. On the other hand, these three substances inhibited heparin-induced platelet aggregation. These findings, taken together, suggested that EDTA and heparin initiated platelet activation and EDTA-induced platelet aggregation might be a process unrelated to thromboxane A2 production. Heparin may not be a suitable anticoagulant since it aggregates platelets of some healthy individuals.

  14. RANDOMIZED DOUBLE BLIND COMPARISON OF TWO BRANDS OF CLOPIDOGREL IN INHIBITION OF PLATELET AGGREGATION

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    Hikmatullah Jan

    2010-10-01

    Full Text Available Objectives: To compare the anti platelet effects of locally manufactured clopidogrel with the anti platelet effect of clopidogrel manufactured by multinational pharmaceutical abroad. Methodology: A total of 118 subjects were enrolled, 18 to 65 years of age, who presented with suspected ischemic heart disease and were randomly assigned to receive either drug A (Pidogrel or drug B (Plavix in a double blind manner for 7 days. Platelet aggregation was measured in both the groups at baseline and at final visit. Results: Base line platelet aggregability in both drug groups was not significantly different (p=0.317 Mean reduction in platelet aggregation by drug-A was 8.47+/- 0.45 ohms (p<0.001 and mean reduction in platelet aggregation by drug-B was 8.62+/- 0.46 (p<0.001. The difference in platelet aggregability at day 7(follow up between the two groups was not statistically significant i.e., was the same. Conclusion: Locally manufactured clopidogrel is equally effective as that manufactured by the multinational company abroad giving us the added advantage of cost effectiveness

  15. Cilostazol inhibits accumulation of triglyceride in aorta and platelet aggregation in cholesterol-fed rabbits.

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    Hideki Ito

    Full Text Available Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities.

  16. Phase analysis of platelet aggregation in acute disturbances of cerebral circulation.

    Science.gov (United States)

    Petrova, T R; Pavlishchuk, S A; Grigoriev, G I

    1975-01-01

    In 120 patients with atherosclerosis, complicated in 43 patients by a haemorrhagic, in 47 patients by an ischaemic, and in 30 patients by a transient cerebral insult, phase analysis of platelet aggregation was performed by the turbidimetric method according to Born with graphic recording according to O'Brien. An increase in the platelet activity was found in ischaemic insult, manifesting itself by the occurrence of spontaneous aggregationin 60% of the cases, an acceleration of ADP-induced aggregation, and the second aggregation phase in all patients examined. A direct correlation was revealed between the secondary aggregation and the intensity of spontaneous and of ADP-induced aggregation, and the possibility of a transformation of the spontaneous into the secondary aggregation of platelets was demonstrated. Haemorrhagic insults were characterized by the absence of spontaneous and secondary aggregation and by the suppression of ADP-induced aggregation. In a transient insult, the mean values of the aggregatogram items did differ from normal. In vitro, the role of increased permeability of platelet membranes in the mechanism triggering off spontaneous aggregation and the second phase of ADP-induced aggregation was documented.

  17. Migration distance-based platelet function analysis in a microfluidic system

    OpenAIRE

    Song, Suk-Heung; Lim, Chae-Seung; Shin, Sehyun

    2013-01-01

    Aggregation and adhesion of platelets to the vascular wall are shear-dependent processes that play critical roles in hemostasis and thrombosis at vascular injury sites. In this study, we designed a simple and rapid assay of platelet aggregation and adhesion in a microfluidic system. A shearing mechanism using a rotating stirrer provided adjustable shear rate and shearing time and induced platelet activation. When sheared blood was driven through the microchannel under vacuum pressure, shear-a...

  18. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of (1-/sup 14/C)arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva.

  19. Duration of exposure to high fluid shear stress is critical in shear-induced platelet activation-aggregation.

    Science.gov (United States)

    Zhang, Jian-ning; Bergeron, Angela L; Yu, Qinghua; Sun, Carol; McBride, Latresha; Bray, Paul F; Dong, Jing-fei

    2003-10-01

    Platelet functions are increasingly measured under flow conditions to account for blood hydrodynamic effects. Typically, these studies involve exposing platelets to high shear stress for periods significantly longer than would occur in vivo. In the current study, we demonstrate that the platelet response to high shear depends on the duration of shear exposure. In response to a 100 dyn/cm2 shear stress for periods less than 10-20 sec, platelets in PRP or washed platelets were aggregated, but minimally activated as demonstrated by P-selectin expression and binding of the activation-dependent alphaIIbbeta3 antibody PAC-1 to sheared platelets. Furthermore, platelet aggregation under such short pulses of high shear was subjected to rapid disaggregation. The disaggregated platelets could be re-aggregated by ADP in a pattern similar to unsheared platelets. In comparison, platelets that are exposed to high shear for longer than 20 sec are activated and aggregated irreversibly. In contrast, platelet activation and aggregation were significantly greater in whole blood with significantly less disaggregation. The enhancement is likely via increased collision frequency of platelet-platelet interaction and duration of platelet-platelet association due to high cell density. It may also be attributed to the ADP release from other cells such as red blood cells because increased platelet aggregation in whole blood was partially inhibited by ADP blockage. These studies demonstrate that platelets have a higher threshold for shear stress than previously believed. In a pathologically relevant timeframe, high shear alone is likely to be insufficient in inducing platelet activation and aggregation, but acts synergistically with other stimuli.

  20. Comparative Effects of α-, β-, and γ-Carbolines on Platelet Aggregation and Lipid Membranes

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    Hironori Tsuchiya

    2011-01-01

    Full Text Available Cigarette smoking and alcohol consumption possibly affect platelet functions. To verify the hypothesis that some α-, β-, and γ-carboline components in cigarette smoke and alcoholic beverages may change platelet aggregability, their effects on human platelets were determined by aggregometry together with investigating their membrane effects by turbidimetry. Carbolines inhibited platelet aggregation induced by five agents with the potency being 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole > 3-amino-1-methyl-5H-pyrido[4,3-b]indole > 1-methyl-9H-pyrido[3,4-b]indole. The most potent 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole showed 50% aggregation-inhibitory concentrations of 6–172 μM. Both γ-carbolines interacted with phosphatidylcholine membranes to lower the lipid phase transition temperature with the potency correlating to the antiplatelet activity, suggesting that the interaction with platelet membranes to increase their fluidity underlies antiplatelet effects. Given their possible concentration and accumulation in platelets, γ- and β-carbolines would provide cigarette smokers and alcohol drinkers with reduced platelet aggregability, and they may be responsible for the occurrence of hemorrhagic diseases associated with heavy smoking and alcoholics.

  1. Inhibition of platelet aggregation by polyaspartoyl L-arginine and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Yin-ye WANG; Zhi-yu TANG; Min DONG; Xiao-yan LIU; Shi-qi PENG

    2004-01-01

    AIM: To observe the oral anti-platelet efficacy and the potential action mechanism of polyaspartoyl L-arginine (PDR), a new L-arginine rich compound. METHODS: Platelet aggregation was conducted by Born's method;bleeding time was determined using tail's bleeding time in mice; platelet adhesion was carried out with glass bottle method; nitric oxide (NO) was tested with Griess' method; and cAMP, thromboxane B2 (TXB2) and 6-keto-PGF1a were assessed with commercial kits. RESULTS: The inhibition by PDR (15-60 mg/kg ig or 10 mg/kg iv) of platelet aggregation induced by adenosine diphosphate (ADP), collagen or thrombin at 1 h after oral administration or at 20 min after iv injection for rats (P<0.01), and its (15 mg/kg, ig) inhibition of ADP-induced platelet aggregation for rabbits during 6 h after administration were observed. PDR (15-60 mg/kg) prolonged the bleeding time of mice (P<0.05) and (30 mg/kg) increased NO concentration in plasma. On the other hand PDR did not change the contents of cAMP in platelet and TXB2 or 6-keto-PGF1a in plasma. CONCLUSION: PDR is a novel, oral effective platelet aggregation inhibitor and its action mechanism possibly related to increasing NO generation.

  2. Inhibition of human platelet aggregation in vitro by standardized extract of Wendtia calycina

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    Milagros Garcia Mesa

    2011-10-01

    Full Text Available Wendtia calycina (Griseb. Griseb., Vivianiaceae, is a Paraguayan herbaceous plant commonly known as burrito. Our previous study indicated that burrito leaves are a very good source of phenylpropanoid glycosides, principally verbascoside. From W. calycina leaves, a standardized, water-soluble extract rich in phenylpropanoid glycosides (WSE has been developed on an industrial scale to be used as a food supplement, cosmetic, phytomedicine, and ingredient of different formulations. In this study, we investigated the effect of the WSE on human platelet aggregation in vitro induced by adenosine diphosphate (ADP, epinephrine (EPN, collagen (COL or arachidonic acid (AA. WSE, concentration-dependently, inhibited ADP and EP-induced human platelet aggregation (IC50 were 0.82±0.15 mg/mL and 0.41±0.02 mg/mL, respectively. It did not inhibit collagen-induced platelet aggregation, thus suggesting a selectivity for the ADP-induced platelet activation pathways.

  3. Bacillus pasteurii urease shares with plant ureases the ability to induce aggregation of blood platelets.

    Science.gov (United States)

    Olivera-Severo, D; Wassermann, G E; Carlini, C R

    2006-08-15

    Ureases (EC 3.5.1.5) are highly homologous enzymes found in plants, bacteria and fungi. Canatoxin, an isoform Canavalia ensiformis urease, has several biological properties unrelated to its ureolytic activity, like platelet-aggregating and pro-inflammatory effects. Here, we describe that Bacillus pasteurii urease (BPU) also induces aggregation of rabbit platelets, similar to the canatoxin-induced effect (ED(50) 0.4 and 0.015 mg/mL, respectively). BPU induced-aggregation was blocked in platelets pretreated with dexamethasone and esculetin, a phospholipase A(2) and a lipoxygenase inhibitor, respectively, while platelets treated with indomethacin, a cyclooxygenase inhibitor, showed increased response to BPU. Methoxyverapamil (Ca(2+) channel blocker) and AMP (ADP antagonist) abrogated urease-induced aggregation, whereas the PAF-acether antagonist Web2170 had no effect. We concluded that platelet aggregation induced by BPU is mediated by lipoxygenase-derived eicosanoids and secretion of ADP from the platelets through a calcium-dependent mechanism. Potential relevance of these findings for bacterium-plant interactions and pathogenesis of bacterial infections are discussed.

  4. Platelet aggregation measurement for assessment of hemostasis failure mechanisms in patients with gastroduodenal ulcer bleeding

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    Barinov E

    2013-08-01

    Full Text Available Edward Barinov,1 Oksana Sulaieva,1 Yuriy Lyakch,2 Vitaliy Guryanov,2 Petr Kondratenko,3 Yevgeniy Radenko3 1Department of Histology, Cytology, and Embryology, 2Department of Medical, Biological Physics, Medical Informatics, and Biostatistics, 3Department of Surgery and Endoscopy, M Gorky Donetsk National Medical University, Donetsk, Ukraine Background: The purpose of this study was to identify factors associated with the risk of unsustainable hemostasis in patients with gastric and duodenal ulcer bleeding by in vitro assessment of platelet reactivity using artificial neural networks. Methods: Patients with gastroduodenal ulcers complicated by bleeding were studied. Platelet aggregation was measured using aggregometry with adenosine diphosphate 5 µM, epinephrine 2.5 µM, 5-hydroxytryptophan 10 µM, collagen 1 µM, and thrombin 0.06 NIH Unit/mL as agonists. Multiple logistic regression was used to evaluate the independent relationship between demographic, clinical, endoscopic, and laboratory data and in vitro assessment of platelet reactivity and local parameters of hemostasis in patients with ulcer bleeding. Results: Analysis of platelet aggregation in patients with gastroduodenal ulcer bleeding allowed the variability of platelet response to different agonists used in effective concentration which induces 50% platelet aggregation (EC50 to be established. The relationship between platelet aggregation and the spatial-temporal characteristics of ulcers complicated by bleeding was demonstrated. Adrenoreactivity of platelets was associated with time elapsed since the start of ulcer bleeding and degree of hemorrhage. The lowest platelet response to collagen and thrombin was detected in patients with active bleeding (P< 0.001 and unsustainable recent bleeding (P < 0.01. Decreased adenosine diphosphate-induced platelet aggregation in patients with ulcer bleeding was correlated with the platelet response to thrombin (r = 0.714, P < 0.001 and collagen (r

  5. Angiotensin II AT1 receptor antagonists inhibit platelet adhesion and aggregation by nitric oxide release.

    Science.gov (United States)

    Kalinowski, Leszek; Matys, Tomasz; Chabielska, Ewa; Buczko, Włodzimierz; Malinski, Tadeusz

    2002-10-01

    This study investigated the process of nitric oxide (NO) release from platelets after stimulation with different angiotensin II type 1 (AT1)-receptor antagonists and its effect on platelet adhesion and aggregation. Angiotensin II AT1-receptor antagonist-stimulated NO release in platelets was compared with that in human umbilical vein endothelial cells by using a highly sensitive porphyrinic microsensor. In vitro and ex vivo effects of angiotensin II AT1-receptor antagonists on platelet adhesion to collagen and thromboxane A2 analog U46619-induced aggregation were evaluated. Losartan, EXP3174, and valsartan alone caused NO release from platelets and endothelial cells in a dose-dependent manner in the range of 0.01 to 100 micro mol/L, which was attenuated by NO synthase inhibitor N(G)-nitro-L-arginine methyl ester. The angiotensin II AT1-receptor antagonists had more than 70% greater potency in NO release in platelets than in endothelial cells. The degree of inhibition of platelet adhesion (collagen-stimulated) and aggregation (U46619-stimulated) elicited by losartan, EXP3174, and valsartan, either in vitro or ex vivo, closely correlated with the NO levels produced by each of these drugs alone. The inhibiting effects of angiotensin II AT1-receptor antagonists on collagen-stimulated adhesion and U46619-stimulated aggregation of platelets were significantly reduced by pretreatment with N(G)-nitro-L-arginine methyl ester. Neither the AT2 receptor antagonist PD123319, the cyclooxygenase synthase inhibitor indomethacin, nor the selective thromboxane A2/prostaglandin H2 receptor antagonist SQ29,548 had any effect on angiotensin II AT1-receptor antagonist-stimulated NO release in platelets and endothelial cells. The presented studies clearly indicate a crucial role of NO in the arterial antithrombotic effects of angiotensin II AT1-receptor antagonists.

  6. Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function.

    Science.gov (United States)

    Osman, Abdimajid; Hitzler, Walter E; Meyer, Claudius U; Landry, Patricia; Corduan, Aurélie; Laffont, Benoit; Boilard, Eric; Hellstern, Peter; Vamvakas, Eleftherios C; Provost, Patrick

    2015-01-01

    Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen+ ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin+ UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p platelet aggregation response to ADP (p platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established.

  7. The Effect of Ginger (Zingiber officinale on Platelet Aggregation: A Systematic Literature Review.

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    Wolfgang Marx

    Full Text Available The potential effect of ginger on platelet aggregation is a widely-cited concern both within the published literature and to clinicians; however, there has been no systematic appraisal of the evidence to date.Using the PRISMA guidelines, we systematically reviewed the results of clinical and observational trials regarding the effect of ginger on platelet aggregation in adults compared to either placebo or baseline data. Studies included in this review stipulated the independent variable was a ginger preparation or isolated ginger compound, and used measures of platelet aggregation as the primary outcome.Ten studies were included, comprising eight clinical trials and two observational studies. Of the eight clinical trials, four reported that ginger reduced platelet aggregation, while the remaining four reported no effect. The two observational studies also reported mixed findings.Many of the studies appraised for this review had moderate risks of bias. Methodology varied considerably between studies, notably the timeframe studied, dose of ginger used, and the characteristics of subjects recruited (e.g. healthy vs. patients with chronic diseases.The evidence that ginger affects platelet aggregation and coagulation is equivocal and further study is needed to definitively address this question.

  8. Platelet aggregation and serum adenosine deaminase (ADA) activity in pregnancy associated with diabetes, hypertension and HIV.

    Science.gov (United States)

    Leal, Claudio A M; Leal, Daniela B R; Adefegha, Stephen A; Morsch, Vera M; da Silva, José E P; Rezer, João F P; Schrekker, Clarissa M L; Abdalla, Faida H; Schetinger, Maria R C

    2016-07-01

    Platelet aggregation and adenosine deaminase (ADA) activity were evaluated in pregnant women living with some disease conditions including hypertension, diabetes mellitus and human immunodeficiency virus infection. The subject population is consisted of 15 non-pregnant healthy women [control group (CG)], 15 women with normal pregnancy (NP), 7 women with hypertensive pregnancy (HP), 10 women with gestational diabetes mellitus (GDM) and 12 women with human immunodeficiency virus-infected pregnancy (HIP) groups. The aggregation of platelets was checked using an optical aggregometer, and serum ADA activity was determined using the colorimetric method. After the addition of 5 µM of agonist adenosine diphosphate, the percentage of platelet aggregation was significantly (p < 0·05) increased in NP, HP, GDM and HIP groups when compared with the CG, while the addition of 10 µM of the same agonist caused significant (p < 0·05) elevations in HP, GDM and HIP groups when compared with CG. Furthermore, ADA activity was significantly (p < 0·05) enhanced in NP, HP, GDM and HIP groups when compared with CG. In this study, the increased platelet aggregation and ADA activity in pregnancy and pregnancy-associated diseases suggest that platelet aggregation and ADA activity could serve as peripheral markers for the development of effective therapy in the maintenance of homeostasis and some inflammatory process in these pathophysiological conditions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats.

    Science.gov (United States)

    Deng, Zu-Yue; Shan, Wei-Guang; Wang, Shen-Feng; Hu, Meng-Mei; Chen, Yan

    2017-12-01

    Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively. ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold). ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats

  10. Echicetin coated polystyrene beads: a novel tool to investigate GPIb-specific platelet activation and aggregation.

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    Alexey Navdaev

    Full Text Available von Willebrand factor/ristocetin (vWF/R induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways.

  11. Echicetin Coated Polystyrene Beads: A Novel Tool to Investigate GPIb-Specific Platelet Activation and Aggregation

    Science.gov (United States)

    Petunin, Alexey; Clemetson, Kenneth J.; Gambaryan, Stepan; Walter, Ulrich

    2014-01-01

    von Willebrand factor/ristocetin (vWF/R) induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways. PMID:24705415

  12. Inhibitory effects of yuzu and its components on human platelet aggregation.

    Science.gov (United States)

    Kim, Tae-Ho; Kim, Hye-Min; Park, Se Won; Jung, Yi-Sook

    2015-03-01

    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.

  13. Migration distance-based platelet function analysis in a microfluidic system.

    Science.gov (United States)

    Song, Suk-Heung; Lim, Chae-Seung; Shin, Sehyun

    2013-01-01

    Aggregation and adhesion of platelets to the vascular wall are shear-dependent processes that play critical roles in hemostasis and thrombosis at vascular injury sites. In this study, we designed a simple and rapid assay of platelet aggregation and adhesion in a microfluidic system. A shearing mechanism using a rotating stirrer provided adjustable shear rate and shearing time and induced platelet activation. When sheared blood was driven through the microchannel under vacuum pressure, shear-activated platelets adhered to a collagen-coated surface, causing blood flow to significantly slow and eventually stop. To measure platelet adhesion and aggregation, the migration distance (MD) of blood through the microchannel was monitored. As the microstirrer speed increased, MD initially decreased exponentially but then increased beyond a critical rpm. For platelet-excluded blood samples, there were no changes in MD with increasing stirrer speed. These findings imply that the stirrer provided sufficiently high shear to activate platelets and that blood MD is a potentially valuable index for measuring the shear-dependence of platelet activation. Our microfluidic system is quick and simple, while providing a precise assay to measure the effects of shear on platelet aggregation and adhesion.

  14. 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.

    2009-01-01

    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

  15. Glycoprotein IIb/IIIa and P2Y12 Induction by Oligochitosan Accelerates Platelet Aggregation

    Science.gov (United States)

    Halim, Ahmad Sukari; Hussein, Abdul Rahim; Ujang, Zanariah

    2014-01-01

    Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0.45 mL collagen, 8% NO-CMC, oligochitosan (O-C), and oligochitosan 53 (O-C 53)]. We studied gpiibiiia and P2Y12 through flow cytometric analysis and western blotting techniques. The highest expression of gpiibiiia was observed with Lyostypt (74.3 ± 7.82%), followed by O-C (65.5 ± 7.17%). Lyostypt and O-C resulted in gpiibiiia expression increases of 29.2% and 13.9%, respectively, compared with blood alone. Western blot analysis revealed that only O-C 53 upregulated the expression of P2Y12 (1.12 ± 0.03-fold) compared with blood alone. Our findings suggest that the regulation of gpiibiiia and P2Y12 levels could be clinically useful to activate platelets to reach hemostasis. Further, we show that the novel oligochitosan is able to induce the increased expression of gpiibiiia and P2Y12, thus accelerating platelet aggregation in vitro. PMID:25247182

  16. Anti-aggregation action of ultraviolet irradiation on platelet-rich plasma in the presence of antioxidants

    Energy Technology Data Exchange (ETDEWEB)

    Roshchupkin, D.I.; Anosov, A.K.; Potapenko, A.Ya. (2nd Moscow Medical Institute, Moscow (USSR). Dept. of Biophysics)

    1983-05-01

    UV irradiation of platelet-rich plasma (PRP) results in the inhibition of ADP-induced platelets aggregation. This is accounted for by the long-living photoproducts formed in plasma. Platelets destruct these photoproducts in the dark after irradiation. Lipid antioxidants ..cap alpha..-tocopherol and BHT administered in PRP before irradiation reduce the anti-aggregation effect of UV light. Lipid photo-peroxidation is supposed to be responsible for the anti-aggregation effect of UV irradiation on platelet-rich plasma.

  17. Anti-aggregation action of ultraviolet irradiation on platelet-rich plasma in the presence of antioxidants

    Energy Technology Data Exchange (ETDEWEB)

    Roshchupkin, D.I.; Anosov, A.K.; Potapenko, A.Ya. (2nd Moscow Medical Institute, Moscow (USSR). Dept. of Biophysics)

    1983-05-01

    UV irradiation of platelet-rich plasma (PRP) results in the inhibition of ADP-induced platelet aggregation. This is accounted for by the long-living photoproducts formed in plasma. Platelets destroy these photoproducts in the dark after irradiation. Lipid antioxidants ..cap alpha..-tocopherol and BHT administered in PRP before irradiation reduce the anti-aggregation effect of UV light. Lipid photo-peroxidation is supposed to be responsible for the anti-aggregation effect of UV irradiation on platelet-rich plasma.

  18. Determination of serum aluminum, platelet aggregation and lipid peroxidation in hemodialyzed patients

    Directory of Open Access Journals (Sweden)

    T.J.C. Neiva

    2002-03-01

    Full Text Available Aluminum (Al3+ overload is frequently associated with lipid peroxidation and neurological disorders. Aluminum accumulation is also reported to be related to renal impairment, anemia and other clinical complications in hemodialysis patients. The aim of the present study was to determine the degree of lipid peroxidation, platelet aggregation and serum aluminum in patients receiving regular hemodialytic treatment. The level of plasma lipid peroxidation was evaluated on the basis of thiobarbituric acid reactive substances (TBARS. Mean platelet peroxidation in patients undergoing hemodialysis was significantly higher than in normal controls (2.7 ± 0.03 vs 1.8 ± 0.06 nmol/l, P<0.05. Platelet aggregation and serum aluminum levels were determined by a turbidimetric method and atomic absorption spectrophotometry, respectively. Serum aluminum was significantly higher in patients than in normal controls (44.5 ± 29 vs 10.8 ± 2.5 µg/l, P<0.05. Human blood platelets were stimulated with collagen (2.2 µg/ml, adenosine diphosphate (6 µM and epinephrine (6 µM and showed reduced function with the three agonists utilized. No correlation between aluminum levels and platelet aggregation or between aluminum and peroxidation was observed in hemodialyzed patients.

  19. Prognostic significance of thrombocytosis, platelet parameters and aggregation rates in epithelial ovarian cancer.

    Science.gov (United States)

    Ma, Xuegong; Wang, Yingmei; Sheng, Hongna; Tian, Wenyan; Qi, Zheng; Teng, Fei; Xue, Fengxia

    2014-01-01

    The aim of this study is to investigate the impact of preoperative platelet counts, parameters and aggregation rates (maximal aggregation rate: MAR) on prognosis in patients with epithelial ovarian cancer (EOC). Preoperative platelet count, parameters and MAR in 182 EOC patients, 122 patients with benign ovarian tumor and 150 healthy women were retrospectively analyzed. The correlation between thrombocytosis, platelet parameters, MAR and clinicopathological factors were evaluated in EOC. Forty-five (24.73%) EOC patients had preoperative thrombocytosis in this study. The mean platelet count in the EOC group was significantly higher than that of benign and healthy groups (P thrombocytosis and MAR was observed in EOC patients (r = 0.694, P thrombocytosis were found to have significantly higher grade (P = 0.048), more advanced stage (P = 0.045), higher level carbohydrate antigen-125 (P = 0.007) and greater likelihood of suboptimal cytoreduction (P = 0.035). EOC patients with both thrombocytosis and high MAR were found to have shorter progression-free survival (P = 0.001)and overall survival (P = 0.004). The combination of thrombocytosis and MAR, as well as stage and optimal cytoreduction, retained significance as an independent prognostic factor for overall survival. Thrombocytosis, accompanied by increasing of platelet aggregation rates, is associated with more aggressive tumor biology in EOC. The combination of thrombocytosis and MAR is an independent negative prognostic factor for overall survival in EOC patients. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  20. Plasma pharmacological study on Da Huang Zhe Chong capsule on platelet aggregation of normal person

    Institute of Scientific and Technical Information of China (English)

    WANG Dong-sheng; CHEN Fang-ping; XIAO Chang-jiang; HE Shi-lin; FU Bin; LI Xin; CAO Xing-yu; CHEN Yan; XIE Qin-zhi

    2005-01-01

    Objective To develop a plasma pharmacological method evaluates the effect of Da Huang Zhe Chong capsule on platelet aggregation and its mechanism, which is a representative Traditional Chinese Medicine Patent Prescription Promoting blood circulation by removing blood stasis. Methods Platelets specimens from healthy volunteers made serum and plasma with medicine, while platelet PRP were separated, which were divided into 8groups,i.e. auto-serum, allo-serum, serum with Da Huang Zhe Chong capsule , serum with aspirin, auto-plasma, plasma with Da Huang Zhe Chong capsule, plasma with aspirin, every group added to serum and plasma to hatch. After ADP and adrenalin were added into the specimens and hatched, the effects of specimens on platelet aggregation were observed. Results After ADP adrenalin were added, all the serum groups did not present platelet aggregation,while all the plasma group presented platelet aggregation. P1, P5, Pmax, t and TM have no significant difference (P>0. 05) between auto-plasma group and allo-plasma group induced by ADP and adrenalin. P1, P5, t and Pmax have significant differences (P<0. 01) and TM decreased significantly (P<0. 05) comparing plasma group with Da Huang Zhe Chong capsule and plasma group of aspirin to allo-plasma group. P1, t and Pmax have significant difference (P<0.05), and P5 and TM are simulate comparing plasma group with Da Huang Zhe Chong capsule to plasma group of aspirin. P1, P5, t and Pmax have significant differences (P<0. 01), P1, TM have also significant(P<0. 05), comparing plasma group of Da Huang Zhe Chong capsule with plasma of aspirin to allo-plasma group induced by adrenalin. P1 ,P5 and Pmax have significant differences (P<0.05), and t and Pmax are simulate comparing plasma group with Da Huang Zhe Chong capsule with plasma group of aspirin. Conclusion The serum pharmacological study is inappropriate to study platelet aggregation in vitro. The plasma pharmacological study is inappropriate to study

  1. Dauricoside, a new glycosidal alkaloid having an inhibitory activity against blood-platelet aggregation.

    Science.gov (United States)

    Hu, S M; Xu, S X; Yao, X S; Cui, C B; Tezuka, Y; Kikuchi, T

    1993-10-01

    Dauricoside (1), a new glycosidal alkaloid, was isolated from the rhizomes of Menispermum dauricum DC. along with dauricine (2), daurisoline (3), dauriporphine (4), menisporphine (5), and 6-O-demethylmenisporphine (6), and its structure was determined by means of spectroscopic methods. Compounds 1, 2, and 3 inhibited blood-platelet aggregation induced by adenosine 5'-diphosphate (ADP).

  2. The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia

    NARCIS (Netherlands)

    Chong, B H; Burgess, J; Ismail, F

    1993-01-01

    The platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platel

  3. Sulforaphane prevents human platelet aggregation through inhibiting the phosphatidylinositol 3-kinase/Akt pathway.

    Science.gov (United States)

    Chuang, Wen-Ying; Kung, Po-Hsiung; Kuo, Chih-Yun; Wu, Chin-Chung

    2013-06-01

    Sulforaphane, a dietary isothiocyanate found in cruciferous vegetables, has been shown to exert beneficial effects in animal models of cardiovascular diseases. However, its effect on platelet aggregation, which is a critical factor in arterial thrombosis, is still unclear. In the present study, we show that sulforaphane inhibited human platelet aggregation caused by different receptor agonists, including collagen, U46619 (a thromboxane A2 mimic), protease-activated receptor 1 agonist peptide (PAR1-AP), and an ADP P2Y12 receptor agonist. Moreover, sulforaphane significantly reduced thrombus formation on a collagen-coated surface under whole blood flow conditions. In exploring the underlying mechanism, we found that sulforaphane specifically prevented phosphatidylinositol 3-kinase (PI3K)/Akt signalling, without markedly affecting other signlaling pathways involved in platelet aggregation, such as protein kinase C activation, calcium mobilisation, and protein tyrosine phosphorylation. Although sulforaphane did not directly inhibit the catalytic activity of PI3K, it caused ubiquitination of the regulatory p85 subunit of PI3K, and prevented PI3K translocation to membranes. In addition, sulforaphane caused ubiquitination and degradation of phosphoinositide-dependent kinase 1 (PDK1), which is required for Akt activation. Therefore, sulforaphane is able to inhibit the PI3K/Akt pathway at two distinct sites. In conclusion, we have demonstrated that sulforaphane prevented platelet aggregation and reduced thrombus formation in flow conditions; our data also support that the inhibition of the PI3K/Akt pathway by sulforaphane contributes it antiplatelet effects.

  4. Effect of n-tyrosol on blood viscosity and platelet aggregation.

    Science.gov (United States)

    Plotnikov, M B; Chernysheva, G A; Smol'yakova, V I; Maslov, M Yu; Cherkashina, I V; Krysin, A P; Sorokina, I V; Tolstikova, T G

    2007-01-01

    Experiments on rats showed that n-tyrosol limited the increase in blood viscosity during thermal exposure at a shear rate of 5-300 sec(-1) and inhibited ADP-induced platelet aggregation. The effects of n-tyrosol are comparable to that of pentoxyphylline.

  5. Mildly oxidized HDL decrease agonist-induced platelet aggregation and release of pro-coagulant platelet extracellular vesicles.

    Science.gov (United States)

    Tafelmeier, M; Fischer, A; Orsó, E; Konovalova, T; Böttcher, A; Liebisch, G; Matysik, S; Schmitz, G

    2017-05-01

    Stored platelet concentrates (PLCs) for therapeutic purpose, develop a platelet storage lesion (PSL), characterized by impaired platelet (PLT) viability and function, platelet extracellular vesicle (PL-EV) release and profound lipidomic changes. Whereas oxidized low-density lipoprotein (oxLDL) activates PLTs and promotes atherosclerosis, effects linked to oxidized high-density lipoprotein (oxHDL) are poorly characterized. PLCs from blood donors were treated with native (nHDL) or mildly oxidized HDL (moxHDL) for 5days under blood banking conditions. Flow cytometry, nanoparticle tracking analysis (NTA), aggregometry, immunoblot analysis and mass spectrometry were carried out to analyze PL-EV and platelet exosomes (PL-EX) release, PLT aggregation, protein expression, and PLT and plasma lipid composition. In comparison to total nHDL, moxHDL significantly decreased PL-EV release by -36% after 5days of PLT storage and partially reversed agonist-induced PLT aggregation. PL-EV release positively correlated with PLT aggregation. MoxHDL improved PLT membrane lipid homeostasis through enhanced uptake of lysophospholipids and their remodeling to corresponding phospholipid species. This also appeared for sphingomyelin (SM) and d18:0/d18:1 sphingosine-1-phosphate (S1P) at the expense of ceramide (Cer) and hexosylceramide (HexCer) leading to reduced Cer/S1P ratio as PLT-viability indicator. This membrane remodeling was associated with increased content of CD36 and maturation of scavenger receptor-B1 (SR-B1) protein in secreted PL-EVs. MoxHDL, more potently than nHDL, improves PLT-membrane lipid homeostasis, partially antagonizes PL-EV release and agonist-induced PLT aggregation. Altogether, this may be the result of more efficient phospho- and sphingolipid remodeling mediated by CD36 and SR-B1 in the absence of ABCA1 on PLTs. As in vitro supplement in PLCs, moxHDL has the potential to improve PLC quality and to prolong storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Validity of Particle-Counting Method Using Laser-Light Scattering for Detecting Platelet Aggregation in Diabetic Patients

    Science.gov (United States)

    Nakadate, Hiromichi; Sekizuka, Eiichi; Minamitani, Haruyuki

    We aimed to study the validity of a new analytical approach that reflected the phase from platelet activation to the formation of small platelet aggregates. We hoped that this new approach would enable us to use the particle-counting method with laser-light scattering to measure platelet aggregation in healthy controls and in diabetic patients without complications. We measured agonist-induced platelet aggregation for 10 min. Agonist was added to the platelet-rich plasma 1 min after measurement started. We compared the total scattered light intensity from small aggregates over a 10-min period (established analytical approach) and that over a 2-min period from 1 to 3 min after measurement started (new analytical approach). Consequently platelet aggregation in diabetics with HbA1c ≥ 6.5% was significantly greater than in healthy controls by both analytical approaches. However, platelet aggregation in diabetics with HbA1c < 6.5%, i.e. patients in the early stages of diabetes, was significantly greater than in healthy controls only by the new analytical approach, not by the established analytical approach. These results suggest that platelet aggregation as detected by the particle-counting method using laser-light scattering could be applied in clinical examinations by our new analytical approach.

  7. Uridine Triphosphate Thio Analogues Inhibit Platelet P2Y12 Receptor and Aggregation

    Science.gov (United States)

    Gündüz, Dursun; Tanislav, Christian; Sedding, Daniel; Parahuleva, Mariana; Santoso, Sentot; Troidl, Christian; Hamm, Christian W.; Aslam, Muhammad

    2017-01-01

    Platelet P2Y12 is an important adenosine diphosphate (ADP) receptor that is involved in agonist-induced platelet aggregation and is a valuable target for the development of anti-platelet drugs. Here we characterise the effects of thio analogues of uridine triphosphate (UTP) on ADP-induced platelet aggregation. Using human platelet-rich plasma, we demonstrate that UTP inhibits P2Y12 but not P2Y1 receptors and antagonises 10 µM ADP-induced platelet aggregation in a concentration-dependent manner with an IC50 value of ~250 µM. An eight-fold higher platelet inhibitory activity was observed with a 2-thio analogue of UTP (2S-UTP), with an IC50 of 30 µM. The 4-thio analogue (4S-UTP) with an IC50 of 7.5 µM was 33-fold more effective. A three-fold decrease in inhibitory activity, however, was observed by introducing an isobutyl group at the 4S- position. A complete loss of inhibition was observed with thio-modification of the γ phosphate of the sugar moiety, which yields an enzymatically stable analogue. The interaction of UTP analogues with P2Y12 receptor was verified by P2Y12 receptor binding and cyclic AMP (cAMP) assays. These novel data demonstrate for the first time that 2- and 4-thio analogues of UTP are potent P2Y12 receptor antagonists that may be useful for therapeutic intervention. PMID:28146050

  8. Effects of heparin on platelet aggregation and release and thromboxane A2 production

    Energy Technology Data Exchange (ETDEWEB)

    Mohammad, S.F.; Anderson, W.H.; Smith, J.B.; Chuang, H.Y.; Mason, R.G.

    1981-08-01

    Heparin, when added to citrated platelet-rich plasma (PRP), caused potentiation of platelet aggregation and the release reaction induced by the aggregating agents adenosine diphosphate (ADP), arachidonic acid, collagen, and epinephrine. At low concentrations (4.7 x 10(-5) M) arachidonic acid failed to cause aggregation of platelets in citrated PRP. However, in the presence of heparin, the same concentration of arachidonic acid caused aggregation. Examination of PRP for the presence of thromboxane A2 (TxA2) by use of a bioassay revealed that heparin also stimulated release of TxA2. This finding indicated that platelets released more TxA2 when they were challenged by low concentrations of arachidonic acid in the presence of heparin than in its absence. Platelets were labeled with /sup 3/H-arachidonic acid and /sup 14/C-serotonin, and attempts were made to determine whether heparin stimulated the platelet release reaction first with subsequent increased production of TxA2, or alternatively, whether heparin stimulated TxA2 production first with subsequent enhancement of the release reaction. In view of the demonstrated simultaneous release of /sup 14/C-serotonin and /sup 3/H-arachidonic acid metabolites, it appeared that either release of /sup 14/C and /sup 3/H occurs concurrently or, even if one of these events is dependent on the other, both events take place in rapid succession. Timed sequential studies revealed that in the presence of arachidonic acid, the addition of heparin hastened the apparently simultaneous release of both /sup 14/C and /sup 3/H.

  9. Iron-induced platelet aggregation measurement : a novel method to measure platelet function in stenting for ST segment elevation myocardial infarction

    NARCIS (Netherlands)

    Smit, J. J. J.; van Oeveren, W.; Ottervanger, J. P.; Slingerland, R. J.; Remijn, J. A.; Zijlstra, F.; van 't Hof, A. W. J.

    2009-01-01

    Iron and (stainless) steel are potent platelet aggregation activators, and may be involved in stent thrombosis, a serious complication after intracoronary stenting. Current platelet function tests are suboptimal, because of inappropriate agonists and/or lack of reproducibility. We tested the feasibi

  10. No clinically relevant interaction between sugammadex and aspirin on platelet aggregation and coagulation parameters.

    Science.gov (United States)

    de Kam, Pieter-Jan; El Galta, Rachid; Kruithof, Annelieke C; Fennema, Hein; van Lierop, Marie-José; Mihara, Katsuhiro; Burggraaf, Jacobus; Moerland, Matthijs; Peeters, Pierre; Troyer, Matthew D

    2013-12-01

    This study evaluated interaction potential between sugammadex and aspirin on platelet aggregation. This was a randomized, double-blind, placebo-controlled, four-period crossover study in 26 healthy adult males. Treatments were i.v. placebo, i.v. sugammadex 4 mg/kg, and i.v. placebo/sugammadex with oncedaily oral aspirin 75 mg. Primary objective was to assess interaction between sugammadex and aspirin on platelet aggregation using collagen-induced whole-blood aggregometry. Effects on activated partial thromboplastin time (APTT) and cutaneous bleeding time were also evaluated. Platelet aggregation and APTT were evaluated by geometric mean ratios, using area-under-effect curves 3 - 30 minutes after sugammadex/placebo dosing. Bleeding time ratio was evaluated at 5 minutes post-dosing. Non-inferiority margins were pre-specified via literature review. Type I error was controlled using a hierarchical strategy. Ratio for platelet aggregation for aspirin with sugammadex vs. aspirin alone was 1.01, with lower limit of two-sided 90% CI of 0.91(above non-inferiority margin of 0.75). Ratio for statistical interaction between sugammadex and aspirin on APTT was 1.01, with upper 90% CI of 1.04 (below non-inferiority margin of 1.50), and for sugammadex vs. placebo alone was 1.06, with an upper 90% CI of 1.07 (below non-inferiority margin of 1.50). Ratio for bleeding time for aspirin with sugammadex vs. aspirin plus placebo was 1.20, with upper 90% CI of 1.45 (below non-inferiority margin of 1.50). Sugammadex was generally well tolerated. There was no clinically relevant reduction in platelet aggregation with addition of sugammadex 4 mg/kg to aspirin. Pre-determined non-inferiority margins were not exceeded for bleeding time and APTT.

  11. Effect of dietary copper on platelet volume and aggregation in men

    Energy Technology Data Exchange (ETDEWEB)

    Milne, D.B.; Gallagher, S.K. (Dept. of Agriculture, Grand Forks, ND (United States))

    1991-03-15

    A study conducted in the authors' laboratory indicated that mean platelet (PLT) volume (MPV) in rats was affected by dietary copper. They suggested that PLT aggregation may also be affected. Ten men aged 19 to 39 yrs, who lived in a metabolic unit, participated in a study that was divided into four six-week dietary periods in a 2 {times} 2 factorial design with 0.65 and 2.65 mg Cu/d and 0.75 and 2.75 g cystine/d as variables. Plasma copper was not significantly affected by the dietary manipulations, but enzymatically measured ceruloplasmin (Cp) was significantly depressed during low copper intake. Maximum 5 {mu}M ADP-stimulated PLT aggregation in platelet rich plasma was significantly greater during low copper intake than during high Cu intake. Total platelet count and collagen or epinephrine stimulated PLT aggregation were not significantly affected by dietary treatment. Four men who responded to low copper intake with elevated serum cholesterol and depressed specific activity of Cp had significantly elevated MPV and maximum ADP-stimulated PLT aggregation during low Cu intake. The other six men exhibited only increased PLT aggregation during only the low copper, low cystine dietary period. These data indicate that dietary copper is a factor in PLT function in humans.

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

    Directory of Open Access Journals (Sweden)

    Conglei Li

    2012-01-01

    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.

  13. Fibrin clot structure and platelet aggregation in patients with aspirin treatment failure.

    Directory of Open Access Journals (Sweden)

    Søs Neergaard-Petersen

    Full Text Available BACKGROUND: Aspirin is a cornerstone in prevention of cardiovascular events and modulates both platelet aggregation and fibrin clot formation. Some patients experience cardiovascular events whilst on aspirin, often termed aspirin treatment failure (ATF. This study evaluated both platelet aggregation and fibrin clot structure in patients with ATF. METHODS: We included 177 stable coronary artery disease patients on aspirin monotherapy. Among these, 116 (66% had ATF defined as myocardial infarction (MI whilst on aspirin. Platelet aggregation was assessed by Multiplate® aggregometry and VerifyNow®, whereas turbidimetric assays and scanning electron microscopy were employed to study fibrin clot characteristics. RESULTS: Enhanced platelet aggregation was observed in patients with ATF compared with non-MI patients following stimulation with arachidonic acid 1.0 mM (median 161 (IQR 95; 222 vs. 97 (60; 1776 AU*min, p = 0.005 and collagen 1.0 µg/mL (293 (198; 427 vs. 220 (165; 370 AU*min, p = 0.03. Similarly, clot maximum absorbance, a measure of fibrin network density, was increased in patients with ATF (0.48 (0.41; 0.52 vs. 0.42 (0.38; 0.50, p = 0.02, and this was associated with thinner fibres (mean ± SD: 119.7±27.5 vs. 127.8±31.1 nm, p = 0.003 and prolonged lysis time (552 (498; 756 vs. 519 (468; 633 seconds; p = 0.02. Patients with ATF also had increased levels of C-reactive protein (CRP (1.34 (0.48; 2.94 and 0.88 (0.32; 1.77 mg/L, p = 0.01 compared with the non-MI group. Clot maximum absorbance correlated with platelet aggregation (r = 0.31-0.35, p-values<0.001 and CRP levels (r = 0.60, p<0.001. CONCLUSIONS: Patients with aspirin treatment failure showed increased platelet aggregation and altered clot structure with impaired fibrinolysis compared with stable CAD patients without previous MI. These findings suggest that an increased risk of aspirin treatment failure may be identified by measuring both platelet

  14. Fibrin clot structure and platelet aggregation in patients with aspirin treatment failure.

    Science.gov (United States)

    Neergaard-Petersen, Søs; Ajjan, Ramzi; Hvas, Anne-Mette; Hess, Katharina; Larsen, Sanne Bøjet; Kristensen, Steen Dalby; Grove, Erik Lerkevang

    2013-01-01

    Aspirin is a cornerstone in prevention of cardiovascular events and modulates both platelet aggregation and fibrin clot formation. Some patients experience cardiovascular events whilst on aspirin, often termed aspirin treatment failure (ATF). This study evaluated both platelet aggregation and fibrin clot structure in patients with ATF. We included 177 stable coronary artery disease patients on aspirin monotherapy. Among these, 116 (66%) had ATF defined as myocardial infarction (MI) whilst on aspirin. Platelet aggregation was assessed by Multiplate® aggregometry and VerifyNow®, whereas turbidimetric assays and scanning electron microscopy were employed to study fibrin clot characteristics. Enhanced platelet aggregation was observed in patients with ATF compared with non-MI patients following stimulation with arachidonic acid 1.0 mM (median 161 (IQR 95; 222) vs. 97 (60; 1776) AU*min, p = 0.005) and collagen 1.0 µg/mL (293 (198; 427) vs. 220 (165; 370) AU*min, p = 0.03). Similarly, clot maximum absorbance, a measure of fibrin network density, was increased in patients with ATF (0.48 (0.41; 0.52) vs. 0.42 (0.38; 0.50), p = 0.02), and this was associated with thinner fibres (mean ± SD: 119.7±27.5 vs. 127.8±31.1 nm, p = 0.003) and prolonged lysis time (552 (498; 756) vs. 519 (468; 633) seconds; p = 0.02). Patients with ATF also had increased levels of C-reactive protein (CRP) (1.34 (0.48; 2.94) and 0.88 (0.32; 1.77) mg/L, p = 0.01) compared with the non-MI group. Clot maximum absorbance correlated with platelet aggregation (r = 0.31-0.35, p-valuesaspirin treatment failure showed increased platelet aggregation and altered clot structure with impaired fibrinolysis compared with stable CAD patients without previous MI. These findings suggest that an increased risk of aspirin treatment failure may be identified by measuring both platelet function and fibrin clot structure.

  15. Low-dose aspirin (ASA) renders human platelets more vulnerable to inhibition of aggregation by prostacyclin (PGI2).

    Science.gov (United States)

    Philp, R B; Paul, M L

    1983-06-01

    Pre-treatment of human, platelet-rich plasma with concentrations of aspirin that produced 50% or less inhibition of aggregation induced by collagen, arachidonic acid or adenosine diphosphate, significantly increased the % inhibition of platelet aggregation by a low concentration of authentic prostacyclin or by prostacyclin-like activity generated by incubation of rat aorta rings in human platelet-poor plasma. Similarly a single aspirin tablet (325 mg) taken orally by human volunteers significantly increased the sensitivity of their platelets to inhibition of aggregation by authentic prostacyclin (8.1 X 10(-10) M) for 2-48 h after ingestion. Statistical significance was lost at 72 h but the trend was still evident. These results support the contention that low doses of aspirin may be efficacious in the therapy of arterial thromboembolism since this could preserve some arterial prostacyclin-generating activity which might be sufficient to inhibit adhesion and aggregation of the aspirin-treated platelets.

  16. [Anti-platelet aggregation bioassay based quality control for XST capsules].

    Science.gov (United States)

    Han, Bing; Mao, Xin; Han, Shu-xian; Chen, Ying; Xiang, Yan-hua; Ge, Yi-meng; Liao, Fu-long; You, Yun

    2015-12-01

    A in vitro platelet aggregation bioassay was developed for the quality control of XST capsules. The in vitro anti-platelet aggregation effect in rats was observed to detect the bioactivity of XST capsules. Panax notoginseng saponins and Xuesaitong lyophilizedpowder for injection were taken as standard control substances to determine the potency. According to the results, XST capsules showeda significant inhibitory effect on thrombin-induced platelet aggregation in a dose-dependent manner. The in vitro anti-platelet activity oflyophilized powder for injection was stabler than that of Panax notoginseng saponins, and so suitable to serve as a standard control substance. The biological potency of XST capsules compared with standard control substance was detected by using parallel line assay. According to the results, the established bioassay method had a good repeatability (RSD 2.92%). The sample test results could pass thereliability test(linear deviation P > 0.05, parallel deviation P > 0.05). This bioassay method could be used as one of the complementary quality control methods for XST capsules.

  17. C-phycocyanin, a very potent and novel platelet aggregation inhibitor from Spirulina platensis.

    Science.gov (United States)

    Hsiao, George; Chou, Po-Hsiu; Shen, Ming-Yi; Chou, Duen-Suey; Lin, Chien-Huang; Sheu, Joen-Rong

    2005-10-05

    The aim of this study was to systematically examine the inhibitory mechanisms of C-phycocyanin (C-PC), one of the major phycobiliproteins of Spirulina platensis (a blue-green alga), in platelet activation. In this study, C-PC concentration-dependently (0.5-10 nM) inhibited platelet aggregation stimulated by agonists. C-PC (4 and 8 nM) inhibited intracellular Ca2+ mobilization and thromboxane A2 formation but not phosphoinositide breakdown stimulated by collagen (1 microg/mL) in human platelets. In addition, C-PC (4 and 8 nM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser(157) phosphorylation. Rapid phosphorylation of a platelet protein of Mw 47,000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (150 nM). This phosphorylation was markedly inhibited by C-PC (4 and 8 nM). In addition, C-PC (4 and 8 nM) markedly reduced the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 microg/mL)-activated platelets. The present study reports on a novel and very potent (in nanomolar concentrations) antiplatelet agent, C-PC, which is involved in the following inhibitory pathways: (1) C-phycocyanin increases cyclic GMP/VASP Ser157 phosphorylation and subsequently inhibits protein kinase C activity, resulting in inhibition of both P47 phosphorylation and intracellular Ca2+ mobilization, and (2) C-PC may inhibit free radicals (such as hydroxyl radicals) released from activated platelets, which ultimately inhibits platelet aggregation. These results strongly indicate that C-PC appears to represent a novel and potential antiplatelet agent for treatment of arterial thromboembolism.

  18. CONGESTIVE HEART FAILURE IN DOGS IS ASSOCIATED WITH INCREASED PLATELET LEUKOCYTE AGGREGATION MEASURED BY FLOW CYTOMETRY

    DEFF Research Database (Denmark)

    Tarnow, Inge; Andreasen, Susanne SH; Olsen, Lisbeth Høier

    2010-01-01

    CONGESTIVE HEART FAILURE IN DOGS IS ASSOCIATED WITH ENHANCED PLATELET-LEUKOCYTE AGGREGATES - A MARKER FOR PLATELET ACTIVATION. I Tarnow1, LH Olsen2, SHS Andreasen2, SG Moesgaard2, CE Rasmussen2, AT Kristensen1, T Falk2. 1Departments of Small Animal Clinical Sciences and 2Animal and Veterinary Basic...... Sciences, Faculty of Life Science, University of Copenhagen, Denmark. Chronic congestive heart failure (CHF) in humans is associated with abnormal hemostasis, and changes in hemostatic biomarkers carry a poor prognosis. CHF in dogs has been associated with plasma markers of hypercoagulability, however...

  19. [The influence of erythrocyte-derived microvesicles on aggregation of platelets in burn injury].

    Science.gov (United States)

    Levin, G Ya; Sukhareva, E G

    2015-01-01

    Burn Injury is accompanied by a significant homeostasis disorder, including the disorder of primary homeostasis, associated with aggregation of platelets. The role of erythrocyte-derived microvesicles in this process has not undergone thorough research. Microvesicles were isolated from washed erythrocytes after one day of storage by ultracentrifugation at 100000 g. The number of MVs was determined by flow cytometry and was standardized in the samples. Heparin-dependent and heparin-independent antithrombin activity in erythrocyte microvesicles was studied by coagulation method. We studied platelet aggregation induced and not induced by ADP under the conditions of artificial shear flow. It was shown that at the early stage of bum injury the number of erythrocyte-derived microvesicles in blood demonstrated a 4.2-fold ncrease. We determined that microvesicles, derived from the erythrocytes of burn patients displayed a significantly less aggregation activity than the microvesicles from donors. The main reason is a considerably lower antithrombin activity in the erythrocyte microvesicles of bum patients. Thus, we can conclude that the decrease of antiaggregation and antithrombin activity of erythrocyte microvesicles associated with the increase in their concentration in blood contributes to thrombophilia of bum patients. Keywords: erythrocytes, microvesicles, bum injury, platelet aggregation, antithrombin activity

  20. The NLRP3 inflammasome and bruton's tyrosine kinase in platelets co-regulate platelet activation, aggregation, and in vitro thrombus formation.

    Science.gov (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

    2017-01-29

    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.

  1. Effects of ethanol on aggregation, serotonin release, and amyloid precursor protein processing in rat and human platelets.

    Science.gov (United States)

    Ehrlich, Daniela; Humpel, Christian

    2014-01-01

    It is known that oxidative stress leads to amyloid precursor protein (APP) dysregulation in platelets. Ethanol (EtOH) is a vascular risk factor and induces oxidative stress. The aim of the present study was thus to investigate whether EtOH affects APP processing in rat and human platelets. Platelets were exposed to 50 mM EtOH with and without 2 mM calcium-chloride (CaCl₂) for 20 or 180 minutes at 37°C. Platelet aggregation, serotonin release and APP isoforms 130 and 106/110 kDa were analyzed. As a control, 100 mM H₂O₂ was tested in rat platelets. Our data show that EtOH alone did not affect any of the analyzed parameters, whereas CaCl₂ significantly increased aggregation of rat and human platelets. In addition, CaCl₂ alone enhanced serotonin release in rat platelets. EtOH counteracted CaCl₂-induced aggregation and serotonin release. In the presence of CaCl₂, EtOH reduced the 130 kDa APP isoform in rat and human platelets. In conclusion, this study shows that in the presence of CaCl₂, EtOH affects the platelet function and APP processing in rat and human platelets.

  2. Analysis of anti-platelet aggregation components of Rhizoma Zingiberis using chicken thrombocyte extract and high performance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    NIE Hong; MENG Lan-zhen; ZHANG Hui; ZHANG Jian-yu; YIN Zhen; HUANG Xue-song

    2008-01-01

    Background The conventional procedure for screening bioactive components from traditional Chinese medicine is time-consuming,expensive and low efficient.Therefore,some alternative strategies are needed urgently.A novel method for screening anti-platelet aggregation components from oleoresins was developed using chicken thrombocyte extract and high performance liquid chromatography.Methods The anti-platelet aggregation components of oleoresins were combined with receptors,channels and enzymes of chicken thrombocytes under physiological environment.Unbound substances were washed away and bound compounds were eluted using specific phosphate buffered solution(PBS).Compounds released from target sites were collected and analyzed by high performance liquid chromatography and LC-MS.The activity of three compounds which were screened from this model was confirmed using platelet aggregation pharmacology in vivo.Results There were four typical compounds that bound to the thrombocytes:6-gingerol,8-gingerol,6-shogaol and 10-gingerol,and all had shown anti-platelet aggregation activities.Eight-gingerol displayed the best anti-platelet aggregation effect.Conclusions Chicken thromobcyte extract can be used to isolate chemicals that are ligands of the receptor or other bio-targets on the platelet.This may therefore be a simple and efficient method to screen for anti-platelet aggregation compounds from traditional Chinese medicine.

  3. Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment.

    Science.gov (United States)

    Miyata, Kenichi; Takagi, Satoshi; Sato, Shigeo; Morioka, Hiroshi; Shiba, Kiyotaka; Minamisawa, Tamiko; Takami, Miho; Fujita, Naoya

    2014-12-01

    Almost all highly metastatic tumor cells possess high platelet aggregating abilities, thereby form large tumor cell-platelet aggregates in the microvasculature. Embolization of tumor cells in the microvasculature is considered to be the first step in metastasis to distant organs. We previously identified the platelet aggregation-inducing factor expressed on the surfaces of highly metastatic tumor cells and named as Aggrus. Aggrus was observed to be identical to the marker protein podoplanin (alternative names, T1α, OTS-8, and others). Aggrus is frequently overexpressed in several types of tumors and enhances platelet aggregation by interacting with the platelet receptor C-type lectin-like receptor 2 (CLEC-2). Here, we generated a novel single-chain antibody variable region fragment (scFv) by linking the variable regions of heavy and light chains of the neutralizing anti-human Aggrus monoclonal antibody MS-1 with a flexible peptide linker. Unfortunately, the generated KM10 scFv failed to suppress Aggrus-induced platelet aggregation in vitro. Therefore, we performed phage display screening and finally obtained a high-affinity scFv, K-11. K-11 scFv was able to suppress Aggrus-induced platelet aggregation in vitro. Moreover, K-11 scFv prevented the formation of pulmonary metastasis in vivo. These results suggest that K-11 scFv may be useful as metastasis inhibitory scFv and is expected to aid in the development of preclinical and clinical examinations of Aggrus-targeted cancer therapies.

  4. Calprotectin and platelet aggregation in patients with stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Sanne Bøjet Larsen

    Full Text Available Recent studies suggest that the inflammation-associated protein calprotectin may be implicated in the pathogenesis of coronary artery disease (CAD. However, the impact of calprotectin levels on platelet aggregation in CAD patients has never been investigated.We investigated the association between calprotectin levels and platelet aggregation in stable, high-risk CAD patients receiving aspirin as mono antiplatelet therapy. Furthermore, we aimed to investigate independent clinical and laboratory determinants of calprotectin levels.We performed a cross-sectional study including 581 stable, high-risk CAD patients. All patients received 75 mg aspirin daily as mono antiplatelet therapy. Platelet aggregation was assessed by 1 impedance aggregometry (Multiplate Analyzer using arachidonic acid (AA and collagen as agonists and by 2 the VerifyNow Aspirin Assay. Low-grade inflammation was evaluated by calprotectin, high-sensitive C-reactive-protein (hs-CRP and interleukin-6. Platelet activation was assessed by soluble P-selectin, and cyclooxygenase-1 inhibition was evaluated by serum thromboxane B2, both measured by ELISA.Calprotectin levels correlated positively with platelet aggregation according to Multiplate Analyzer (r=0.12, p=0.01. Additionally, calprotectin was positively associated with leukocytes (r=0.33, p<0.0001, hs-CRP (r=0.31, p<0.0001, interleukin-6 (r=0.28, p<0.0001, soluble P-selectin (r=0.10, p=0.02 and serum thromboxane B2 (r=0.10, p=0.02. Type 2 diabetes mellitus was an independent predictor of increased calprotectin levels (p=0.004, and trends were seen for body mass index (p=0.06 and smoking (p=0.07. Compliance with aspirin was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 1.07 [0.52;1.87] ng/mL.Calprotectin levels correlated positively, though weakly, with platelet aggregation and activation as well as serum thromboxane B2 in high-risk, stable CAD patients treated with aspirin.

  5. New Sesquiterpenoids and Anti-Platelet Aggregation Constituents from the Rhizomes of Curcuma zedoaria.

    Science.gov (United States)

    Chen, Jih-Jung; Tsai, Tung-Han; Liao, Hsiang-Ruei; Chen, Li-Chai; Kuo, Yueh-Hsiung; Sung, Ping-Jyun; Chen, Chun-Lin; Wei, Chun-Sheng

    2016-10-17

    Two new sesquiterpenoids-13-hydroxycurzerenone (1) and 1-oxocurzerenone (2)-have been isolated from the rhizomes of Curcuma zedoaria, together with 13 known compounds (3-15). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 13-hydroxycurzerenone (1), 1-oxocurzerenone (2), curzerenone (3), germacrone (4), curcolone (5), procurcumenol (6), ermanin (7), curcumin (8), and a mixture of stigmast-4-en-3,6-dione (12) and stigmasta-4,22-dien-3,6-dione (13) exhibited inhibition (with inhibition % in the range of 21.28%-67.58%) against collagen-induced platelet aggregation at 100 μM. Compounds 1, 5, 7, 8, and the mixture of 12 and 13 inhibited arachidonic acid (AA)-induced platelet aggregation at 100 μM with inhibition % in the range of 23.44%-95.36%.

  6. Detection and characterization of immune complexes by the platelet aggregation test. II. Circulating complexes

    Science.gov (United States)

    Myllylä, G.; Vaheri, A.; Penttinen, K.

    1971-01-01

    Model experiments with preformed antigen–antibody complexes have shown that the platelet aggregation test can be used to characterize immune complexes. The platelet aggregating activity of four sera behaved like antigen–antibody complexes with respect to the effect of added antigen, added antibody and sedimentation in density gradient centrifugation. Two of the sera were from patients with fever of unknown origin. The findings suggest that the two sera contained circulating immune complexes which had both measles hyperimmunization induced and normal specificities. The serum of a patient with fatal subacute hepatitis seemed to contain immune complexes with Australia antigen. It was also positive in many of the autoimmunity tests. One of the sera was from a patient with haemorrhagic varicella in the acute phase of the disease. The patient had received large amounts of γ-globulin. The results suggested the transient presence of circulating immune complexes with varicella specificity. PMID:4102701

  7. Anti-platelet aggregation triterpene saponins from the galls of Sapindus mukorossi.

    Science.gov (United States)

    Huang, Hui-Chi; Tsai, Wei-Jern; Liaw, Chia-Ching; Wu, Shih-Hsiung; Wu, Yang-Chang; Kuo, Yao-Haur

    2007-09-01

    Bioassay-directed fractionation of an ethanolic extract of the galls of Sapindus mukorossi has resulted in the isolation of two new tirucallane-type triterpenoid saponins, sapinmusaponins Q (1) and R (2), along with three known oleanane-type triterpenoid saponins (3-5). Their structures were elucidated on the basis of spectroscopic analysis and chemical hydrolysis. Biological evaluation showed that both sapinmusaponins Q and R demonstrated more potent anti-platelet aggregation activity than aspirin.

  8. Synthesis of huaicarbon A/B and their activating effects on platelet glycoprotein VI receptor to mediate collagen-induced platelet aggregation

    Science.gov (United States)

    Yu, Hongli; Chen, Yeqing; Wu, Hao; Wang, Kuilong; Liu, Liping; Zhang, Xingde

    2017-01-01

    Quercetin and rhamnose were efficiently converted into huaicarbon A/B by heating at 250°C for 10-15 min or at 200°C for 25-30 min. With the optimum molar ratio of quercetin/rhamnose (1:3), huaicarbon A and B yields reached 25% and 16% respectively after heating at 250°C, with 55% quercetin conversion. Huaicarbon A/B both promoted washed platelet aggregation dose-dependently, which was antagonized by an inhibitor of glycoprotein VI (GPVI) receptor. Similarly, they both promoted collagen-induced platelet aggregation in platelet-rich plasma in dose-dependent manners. According to the S type dose-response model, EC50 values of huaicarbon A and huaicarbon B were calculated as 33.48 μM and 48.73 μM respectively. They induced intracellular Ca2+ accumulation that was specifically blocked by GPVI antagonist. Huaicarbon A/B enhanced intracellular Ca2+ accumulation and facilitated collagen-induced platelet aggregation, which were blocked by GPVI antagonist. They were conducive to collagen-induced platelet aggregation by activating platelet GPVI receptor. PMID:28337278

  9. Platelet Aggregation Inhibitors from Aerial Parts of Ruta Chalepensis Grown in Jordan

    Directory of Open Access Journals (Sweden)

    Mayadah B. Shehadeh

    2007-01-01

    Full Text Available From the aerial parts of Ruta chalepensis L., grown in Jordan, two furanocoumarins (bergapten and chalepensin, one flavonoid glycoside (rutin as well as several minor compounds have been isolated. The structural elucidation of these compounds was established based on spectral data (UV, IR, MS,1H-NMR and 13C-NMR. In Jordan, R. chalepensis is recommended for the treatment of rheumatism, mental disorders and menstrual problems. Fresh and dried leaves are used as flavoring agent in food and beverages. Antiplatelet activities of the crude methanolic and ethylacetate extracts in addition to the three isolated major compounds were measured by the aggrometric method according to Beretz and Casenave. Optical aggregometer connected to dual channel recorder was used for measuring aggregation. Both, ethylacetate and methanol extracts inhibited ADP- induced platelet aggregation (ADP-IA of human blood. However, only ethylacetate extract was able to induce 50% inhibition of collagen-induced platelet aggregation (Co-IA platelet rich plasma. Bergapten was more active against ADP-IA compared to chalepensin while the latter was more active against Co-IA compared to bergapten.

  10. Response to platelet-activating factor in human platelets stored and aged in plasma. Decrease in aggregation, phosphoinositide turnover, and receptor affinity

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, S.D.; Morrison, W.J.; Klachko, D.M.

    1989-07-01

    Human platelet concentrates were stored in polyolefin bags at 22 to 24 degrees C on a horizontal shaker for up to 8 days. At different intervals, aliquots of platelet-rich plasma (PRP) were removed aseptically and five variables, i.e., platelet counts, morphology, platelet-activating factor (PAF)-stimulated aggregation, phosphoinositide turnover, and (3H)PAF binding to platelet receptors, were studied. The number of platelets did not change during the 8 days of storage. Scanning electron microscopy of the platelets revealed a gradual morphologic change from biconcave flat discs to irregular, crenated forms. The PAF-induced aggregation of platelets declined with time of storage. A decrease to 50 percent of the Day 1 aggregatory response to PAF was evident on Day 2, and there was a further decline to about 20 percent by Day 6. Similarly, PAF receptor-coupled phosphoinositide turnover, as monitored by 32P incorporation into individual phosphoinositides, decreased dramatically with storage. After 2 to 3 days of storage, the phosphoinositide turnover was reduced to 50 percent of the original response, and it continued to decline to about 25 percent of original response by Day 5 or 6. The binding of (3H)PAF to washed human platelets indicated subtle changes between Days 2 and 4, which became more noticeable by Day 6. These results have raised the possibility of changes in the number of the receptors and/or their affinity for the ligand during storage. We conclude that although the number of platelets was maintained during storage for 8 days, a general deterioration of their responses to PAF occurred at the levels of cell surface receptor, transmembrane signaling (phosphoinositide turnover), and response (aggregation).

  11. Aminoglycosides prevent and dissociate the aggregation of platelets in patients with EDTA-dependent pseudothrombocytopenia.

    Science.gov (United States)

    Sakurai, S; Shiojima, I; Tanigawa, T; Nakahara, K

    1997-12-01

    Although EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is of practical importance because failure to recognize this clinical entity may result in misdiagnosis and subsequent mismanagement of the patients, the pathophysiological nature of EDTA-PTCP remains unknown. To develop an effective way to evaluate the platelet counts in patients with EDTA-PTCP, we introduced aminoglycosides-supplemented anticoagulating agents. When kanamycin was pre-supplemented with EDTA for anticoagulating blood samples from EDTA-PTCP patients there was no significant change in the platelet counts and the morphology of blood cells after 150 min of incubation at room temperature. Furthermore, when kanamycin was added to EDTA-anticoagulated blood samples from EDTA-PTCP patients within 30 min after blood withdrawal, rapid dissociation of platelets without apparent morphological changes of blood cells was observed, and complete blood cell counts as well as the histogram patterns were almost the same as those examined immediately after blood sampling. The dissociation of aggregated platelets was also detected when other antibiotics were used, although it was associated with some extent of morphological changes of blood cells. These findings indicate that the supplementation of aminoglycosides either before or after blood sampling is a useful method for the diagnosis EDTA-PTCP and for the evaluation of platelet counts in patients with EDTA-PTCP.

  12. Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP.

    Science.gov (United States)

    Ottaiano, Tatiana F; Andrade, Sheila S; de Oliveira, Cleide; Silva, Mariana C C; Buri, Marcus V; Juliano, Maria A; Girão, Manoel J B C; Sampaio, Misako U; Schmaier, Alvin H; Wlodawer, Alexander; Maffei, Francisco H A; Oliva, Maria Luiza V

    2017-04-01

    Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin αIIbβ3 through interactions with the KGD/KGE sequence motif in huPK. Integrin αIIbβ3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS(473), ERK1/2, and p38 MAPK, and to Ca(2+) release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and αIIbβ3 (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  13. The naphthoquinone plumbagin suppresses ADP-induced rat platelet aggregation through P2Y1-PLC signaling pathway.

    Science.gov (United States)

    Zhang, Qianrui; Liao, Xiaoyan; Wu, Fangjian

    2017-03-01

    Plumbagin (PLB) isolated from Plumbago zeylanica L (Plumbaginaceae) was evaluated for the suppressive effect and mechanism on ADP induced rat platelet aggregation. Adult male SD rats were randomly divided into control group, clopidogrel group, PLB 25mg/kg group and PLB 50mg/kg group. Clopidogrel (13.5mg/kg per day) and PLB (25 and 50mg/kg per day) were orally given to experimental rats by gavage for seven consecutive days. The antiplatelet properties were assessed by measuring the ADP-induced platelet aggregation rate (Aggmax). The level of cAMP in platelets before aggregation was determined by ELISA. The protein expression of pAkt, Akt, pPLC β3 and PLC β3 in platelets was measured by western blot. Our data indicated that PLB (25 and 50mg/kg) significantly inhibited ADP-induced rat platelet aggregation as well as clopidogrel (13.5mg/kg) in a dose dependent manner compared with the control group. PLB (25 and 50mg/kg) remarkably reduced the ADP-induced PLC β3 phosphorylation but not Akt in platelets as compared with the control group. The present study suggests that PLB exerts a suppressive effect on ADP-induced rat platelet aggregation, at least in part, through P2Y1-PLC signaling pathway.

  14. Orally given gastroprotective capsaicin does not modify aspirin-induced platelet aggregation in healthy male volunteers (human phase I examination).

    Science.gov (United States)

    Sandor, B; Papp, J; Mozsik, Gy; Szolcsanyi, J; Keszthelyi, Zs; Juricskay, I; Toth, K; Habon, Tamas

    2014-12-01

    Capsaicin is a well-known component of red pepper. Recent studies have shown that capsaicin could prevent gastric ulcer provoked by various NSAID-s like acetylsalicylic acid (ASA). Primary objective of this human clinical phase I trial was to investigate whether two different doses of capsaicin co-administered with ASA could alter the inhibitory effect of ASA on platelet aggregation. 15 healthy male subjects were involved in the study and treated orally with 400 μg capsaicin, 800 μg capsaicin, 500 mg ASA, 400 μg capsaicin+500 mg ASA and 800 μg capsaicin+500 mg ASA. Blood was drawn before and 1, 2, 6 and 24 hours after the drug administration. After that epinephrine induced platelet aggregation was measured by optical aggregometry. Between treatments, volunteers had a 6-day wash-out period. Our results showed that capsaicin had no effect on platelet aggregation, while as expected, ASA monotherapy resulted in a significant and clinically effective platelet aggregation inhibition (p ≤ 0.001). The combined ASA-capsaicin therapies reached equivalent effectiveness in platelet aggregation inhibition as ASA monotherapy. Our investigation proved that capsaicin did not influence the inhibitory effect of ASA on platelet aggregation, thus the capsaicin-ASA treatment would combine the antiplatelet effect of ASA with the possible gastroprotection of capsaicin.

  15. Effect of the crude extract of Cestrum parqui on carrageenin-induced rat paw oedema and aggregation of human blood platelets.

    Science.gov (United States)

    Shehnaz, D; Hamid, F; Baqai, F T; Uddin Ahmad, V

    1999-08-01

    An extract of Cestrum parqui aerial parts in methanol:water (1:1) showed inhibition of carrageenin-induced oedema. The aggregation of human blood platelets induced by adenosine diphosphate and platelet activating factor was also inhibited (IC(50)s were 3 and 2 mg/mL, respectively). On the contrary, the extract did not inhibit arachidonic acid-mediated platelet aggregation.

  16. 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

    2008-03-01

    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.

  17. Platelets--an important element of the immune system.

    Science.gov (United States)

    Trzeciak-Ryczek, A; Tokarz-Deptuła, B; Deptuła, W

    2013-01-01

    Platelets are anucleate cells derived from the megakaryocyte series, and have long been considered only as cells responsible for coagulation and the fibrinolysis process. However, recently more data shows that they are also effector cells in the inflammatory response and important elements of the immunological response. Platelets store and release many biologically active substances, including growth factors, cytokines and chemokines (tab. 1), which actively affect i.a. elements of the immune system, and thus become regulators of immunity and mediators of inflammatory response. Their impact on the immune system cells is also associated with the induction of leucocytes and progenitor cells to the site of pathogen permeation or vascular injury inflow, as well as endothelial cells. Interacting with neutrophils, monocytes and lymphocytes, they not only activate them, but also form platelet-leukocyte aggregates that immobilise pathogens and prevent their spreading. Furthermore, platelets are capable of absorbing pathogens, affecting anti-infection immunity of the system. It is also assumed that the presence of receptors on their surface, such as Toll-like receptors (TLRs), affects their initiation and activity of the immunological response.

  18. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study

    OpenAIRE

    Hubbard, G; Wolffram, S; Vos, de, W.M.; Bovy, A.G.; Gibbins, J.; Lovegrove, J

    2006-01-01

    Epidemiological data suggest that those who consume a diet rich in quercetin-containing foods may have a reduced risk of CVD. Furthermore, in vitro and ex vivo studies have observed the inhibition of collagen-induced platelet activation by quercetin. The aim of the present study was to investigate the possible inhibitory effects of quercetin ingestion from a dietary source on collagen-stimulated platelet aggregation and signalling. A double-blind randomised cross-over pilot study was undertak...

  19. Treatment of experimental furcation perforations with mineral trioxide aggregate, platelet rich plasma or platelet rich fibrin in dogs' teeth.

    Science.gov (United States)

    Tawfik, Hosam E; Abu-Seida, Ashraf M; Hashem, Ahmed A; El-Khawlani, Mohammed M

    2016-06-01

    This work evaluates the effect of mineral trioxide aggregate (MTA), platelet rich plasma (PRP) or platelet rich fibrin (PRF) on healing of non-contaminated and contaminated furcation perforations. A total of 192 teeth of 12 dogs was divided into three equal groups according to evaluation period. Each group was further subdivided into MTA, PRP, PRF, negative and positive control subgroups. Each experimental subgroup was further subdivided according to perforation status into non-contaminated and contaminated subdivisions. Root canal therapy was carried out and furcation perforation was made in all teeth except in negative control subgroup. The furcation perforation was repaired immediately in subdivision (1) and after 4 weeks in subdivision (2). The change in vertical bone loss was measured by radiography. Inflammatory cell count, cemental deposition, new bone formation, bone resorption and epithelial proliferation were assessed. Both PRP and PRF demonstrated statistically significant reduction in vertical bone loss and inflammatory cell count than MTA. No significant difference was found between MTA, PRP and PRF in cemental deposition, new bone formation, bone resorption and epithelial proliferation. The non-contaminated teeth demonstrated better treatment outcomes than the contaminated teeth. In conclusion, PRP and PRF are successful treatment options for repairing of furcation perforation in both non-contaminated and contaminated teeth in dogs with superior outcomes in non contaminated teeth.

  20. Platelet response to increased aspirin dose in patients with persistent platelet aggregation while treated with aspirin 81 mg.

    Science.gov (United States)

    Gengo, Fran; Westphal, Erica S; Rainka, Michelle M; Janda, Maria; Robson, Matthew J; Hourihane, J Maurice; Bates, Vernice

    2016-04-01

    This study demonstrates that patients who are taking 81 mg of aspirin and are nonresponsive benefit from a dose of 162 mg or greater vs a different antiplatelet therapy. We identified 100 patients who were nonresponsive to aspirin 81 mg via whole blood aggregometry and observed how many patients became responsive at a dose of 162 mg or greater. Platelet nonresponsiveness was defined as >10 Ω of resistance to collagen 1 µg/mL and/or an ohms ratio of collagen 1 µg/mL to collagen 5 µg/mL >0.5 and/or >6 Ω to arachidonate. Borderline response was defined as an improvement in 1 but not both of the above criteria. Of the initial 100 patients who were nonresponsive to an aspirin dose of 81 mg, 79% became responsive at a dose of 162 mg or >162 mg. Only 6% did not respond to any increase in dose. We believe that patients treated with low-dose aspirin who have significant risk for secondary vascular events should be individually assessed to determine their antiplatelet response. Those found to have persistent platelet aggregation despite treatment with 81 mg of aspirin have a higher likelihood of obtaining an adequate antiplatelet response at a higher aspirin dose.

  1. Platelet aggregation is affected by nitrosothiols in patients with chronic hepatitis: In vivo and in vitro studies

    Institute of Scientific and Technical Information of China (English)

    A Federico; C Loguercio; A Filippelli; M Falciani; C Tuccillo; A Tiso; A Floreani; R Naccarato; F Rossi; C Del Vecchio Blanco

    2007-01-01

    AIM: To investigate the relationship among the number of platelets and plasma levels of S-nitrosothiols (S-NO),nitrite, total non-protein SH (NPSH), glutathione (GSH), cysteine (CYS), malondialdehyde (MDA),4-hydroxininenal (4HNE), tumor necrosis factor-alpha (TNFα) and interleukin (IL)-6 in patients with chronic hepatitis C (CH).METHODS: In vitro the aggregation of platelets derived from controls and CH patients was evaluated before and after the addition of adenosine diphosphate (ADP) and collagen, both in basal conditions and after incubation with nitrosoglutathione (GSNO).RESULTS: In vivo, S-NO plasma levels increased significantly in CH patients and they were significantly directly correlated with platelet numbers. Patients with platelet counts < 150000/μL, had a smaller increase in S-NO, lower levels of GSH, CYS, NPSH, TNFα, and IL-6,and higher levels of nitrite, MDA, and 4-HNE relative to those of patients with platelet counts > 150000/μL.In vitro, the ADP and collagen aggregation time was increased in platelets from patients and not from controls; in addition, platelets from CH patients but not from controls also showed a latency time after exposure to collagen.CONCLUSION: The incubation of platelets with GSNO improved the percentage aggregation and abolished the latency time.

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

    Science.gov (United States)

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

    2014-07-01

    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.

  3. The use of quartz crystal microbalance with dissipation (QCM-D) for studying nanoparticle-induced platelet aggregation

    Science.gov (United States)

    Santos-Martinez, Maria Jose; Inkielewicz-Stepniak, Iwona; Medina, Carlos; Rahme, Kamil; D’Arcy, Deirdre M; Fox, Daniel; Holmes, Justin D; Zhang, Hongzhou; Radomski, Marek Witold

    2012-01-01

    Interactions between blood platelets and nanoparticles have both pharmacological and toxicological significance and may lead to platelet activation and aggregation. Platelet aggregation is usually studied using light aggregometer that neither mimics the conditions found in human microvasculature nor detects microaggregates. A new method for the measurement of platelet microaggregation under flow conditions using a commercially available quartz crystal microbalance with dissipation (QCM-D) has recently been developed. The aim of the current study was to investigate if QCM-D could be used for the measurement of nanoparticle-platelet interactions. Silica, polystyrene, and gold nanoparticles were tested. The interactions were also studied using light aggregometry and flow cytometry, which measured surface abundance of platelet receptors. Platelet activation was imaged using phase contrast and scanning helium ion microscopy. QCM-D was able to measure nanoparticle-induced platelet microaggregation for all nanoparticles tested at concentrations that were undetectable by light aggregometry and flow cytometry. Microaggregates were measured by changes in frequency and dissipation, and the presence of platelets on the sensor surface was confirmed and imaged by phase contrast and scanning helium ion microscopy. PMID:22275839

  4. Inhibition of glutamate receptors reduces the homocysteine-induced whole blood platelet aggregation but does not affect superoxide anion generation or platelet membrane fluidization.

    Science.gov (United States)

    Karolczak, Kamil; Pieniazek, Anna; Watala, Cezary

    2017-01-01

    Homocysteine (Hcy) is an excitotoxic amino acid. It is potentially possible to prevent Hcy-induced toxicity, including haemostatic impairments, by antagonizing glutaminergic receptors. Using impedance aggregometry with arachidonate and collagen as platelet agonists, we tested whether the blockade of platelet NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and kainate receptors with their inhibitors: MK-801 (dizocilpine hydrogen maleate, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), CNQX (7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile) and UBP-302 (2-{[3-[(2S)-2-amino-2-carboxyethyl]-2,6-dioxo-3,6-dihydropyrimidin 1(2H)-yl]methyl}benzoic acid) may hamper Hcy-dependent platelet aggregation. All the tested compounds significantly inhibited Hcy-augmented aggregation of blood platelets stimulated either with arachidonate or collagen. Hcy stimulated the generation of superoxide anion in whole blood samples in a concentration-dependent manner; however, this process appeared as independent on ionotropic glutamate receptors, as well as on NADPH oxidase and protein kinase C, and was not apparently associated with the extent of either arachidonate- or collagen-dependent platelet aggregation. Moreover, Hcy acted as a significant fluidizer of surface (more hydrophilic) and inner (more hydrophobic) regions of platelet membrane lipid bilayer, when used at the concentration range from 10 to 50 µmol/l. However, this effect was independent on the Hcy action through glutamate ionotropic receptors, since there was no effects of MK-801, CNQX or UBP-302 on Hcy-mediated membrane fluidization. In conclusion, Hcy-induced changes in whole blood platelet aggregation are mediated through the ionotopic excitotoxic receptors, although the detailed mechanisms underlying such interactions remain to be elucidated.

  5. Differential inhibition of tumour cell-induced platelet aggregation by the nicotinate aspirin prodrug (ST0702) and aspirin

    Science.gov (United States)

    Medina, Carlos; Harmon, Shona; Inkielewicz, Iwona; Santos-Martinez, Maria Jose; Jones, Michael; Cantwell, Paula; Bazou, Despina; Ledwidge, Mark; Radomski, Marek W; Gilmer, John F

    2012-01-01

    BACKGROUND AND PURPOSE Tumour cell-induced platelet aggregation (TCIPA) facilitates cancer cell invasion, angiogenesis and the formation of metastatic foci. TCIPA can be modulated by pharmacological inhibitors of MMP-2 and ADP; however, the COX inhibitor aspirin did not prevent TCIPA. In this study, we have tested the pharmacological effects of a new group of isosorbide-based aspirin prodrugs on TCIPA. EXPERIMENTAL APPROACH TCIPA was induced in human platelets by mixing with human adenocarcinoma or fibrosarcoma cells under no flow and flow conditions. The release of gelatinases and P-selectin expression during TCIPA were studied by zymography and flow cytometry respectively. KEY RESULTS Tumour cells caused platelet aggregation. This aggregation resulted in the release of MMP-2 and a significant up-regulation of P-selectin on platelets, indicative of platelet activation. Pharmacological modulation of TCIPA revealed that ST0702, one of the aspirin prodrugs, down-regulated TCIPA while aspirin was ineffective. The deacetylated metabolite of ST0702, 5-nicotinate salicylate (ST0702 salicylate), down-regulated both ADP-stimulated platelet aggregation and TCIPA. CONCLUSIONS AND IMPLICATIONS Our results show that ST0702 was an effective inhibitor of TCIPA in vitro. Its deacetylated metabolite may contribute to the effects of ST0702 by inhibiting ADP-mediated TCIPA. PMID:22122360

  6. The use of quartz crystal microbalance with dissipation (QCM-D for studying nanoparticle-induced platelet aggregation

    Directory of Open Access Journals (Sweden)

    Santos-Martinez MJ

    2012-01-01

    Full Text Available Maria Jose Santos-Martinez1–3, Iwona Inkielewicz-Stepniak1,4, Carlos Medina1, Kamil Rahme5,6, Deirdre M D'Arcy1, Daniel Fox3, Justin D Holmes3,5, Hongzhou Zhang3, Marek Witold Radomski3,51School of Pharmacy and Pharmaceutical Sciences, 2School of Medicine, 3Center for Research on Adaptive Nanostructures and Nanodevices, Trinity College Dublin, Dublin, Ireland; 4Department of Medicinal Chemistry, Medical University of Gdansk, Gdansk, Poland; 5Materials and Supercritical Fluids Group, Department of Chemistry and the Tyndall National Institute, University College Cork, Cork, Ireland; 6Department of Sciences, Faculty of Natural and Applied Science, Notre Dame University, Zouk Mosbeh, LebanonAbstract: Interactions between blood platelets and nanoparticles have both pharmacological and toxicological significance and may lead to platelet activation and aggregation. Platelet aggregation is usually studied using light aggregometer that neither mimics the conditions found in human microvasculature nor detects microaggregates. A new method for the measurement of platelet microaggregation under flow conditions using a commercially available quartz crystal microbalance with dissipation (QCM-D has recently been developed. The aim of the current study was to investigate if QCM-D could be used for the measurement of nanoparticle-platelet interactions. Silica, polystyrene, and gold nanoparticles were tested. The interactions were also studied using light aggregometry and flow cytometry, which measured surface abundance of platelet receptors. Platelet activation was imaged using phase contrast and scanning helium ion microscopy. QCM-D was able to measure nanoparticle-induced platelet microaggregation for all nanoparticles tested at concentrations that were undetectable by light aggregometry and flow cytometry. Microaggregates were measured by changes in frequency and dissipation, and the presence of platelets on the sensor surface was confirmed and imaged by

  7. The influence of Rubus idaeus and Rubus caesius leaf extracts on platelet aggregation in whole blood. Cross-talk of platelets and neutrophils.

    Science.gov (United States)

    Dudzinska, Dominika; Bednarska, Katarzyna; Boncler, Magdalena; Luzak, Boguslawa; Watala, Cezary

    2016-07-01

    Recently, polyphenols have gained attention as potential natural cardioprotective therapeutics, due to their antiplatelet, anti-inflammatory and anticoagulant activity. Species belonging to the genus Rubus sp. have been reported to be a source of polyphenolic compounds with antioxidative proprieties and beneficial biological activities. This study investigates the effects of leaf extracts obtained from red raspberry (Rubus idaeus L.) and European dewberry (Rubus caesius L.) on the reactivity of blood platelets. In ADP-stimulated blood, raspberry and dewberry extracts (15 µg/ml) markedly decreased platelet surface membrane expression of activated GPIIbIIIa receptor by 16% and 21%, respectively (P raspberry and by 38-55% for dewberry, P raspberry and dewberry leaf extracts considerably modulated blood platelet reactivity in whole blood: they influenced blood platelet aggregation, possibly via the modulation of the redox status dependent on the oxidative activity of neutrophils.

  8. Roles of Mac-1 and glycoprotein IIb/IIIa integrins in leukocyte-platelet aggregate formation: stabilization by Mac-1 and inhibition by GpIIb/IIIa blockers.

    Science.gov (United States)

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

    2012-01-01

    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.

  9. Anti-platelet Aggregation and Anti-thrombotic Effects of Marine Natural Products Sargahydroquinoic Acid and Sargaquinoic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byonggon; Oh, Sangtae; Kwon, Daeho; Cui, Yuan; Ham, Jungyeob; Shin, Woonseob; Lee, Seokjoon [Kwandong Univ. College of Medicine, Gangneung (Korea, Republic of)

    2013-10-15

    On the basis of the results of the in vitro platelet aggregation inhibition test, we discovered that of SHQA (1) and SQA (2) show a strong inhibitory effect on platelet aggregation. To enable preclinical and clinical studies to be conducted, we synthesized SQA from natural SHQA in high yield. In addition, we confirmed that SHQA (1) and SQA (2) show a fast recovery time from paralysis in the mouse pulmonary thromboembolism model, indicating that they are strong, novel anti-platelet drug candidates. As bleeding is a main side effect of the APDs used clinically, we also plan to conduct a bleeding test with SHQA and SQA and will report these results in a future proper paper. Platelets circulate in blood and their activity is regulated by nitric oxide (NO) and prostaglandin I{sub 2} (PGI{sub 2}) released from endothelial cells in a quiescent state under physiological conditions.

  10. Quantitative investigations of aggregate systems.

    Science.gov (United States)

    Rai, D K; Beaucage, G; Jonah, E O; Britton, D T; Sukumaran, S; Chopra, S; Gonfa, G Goro; Härting, M

    2012-07-28

    Nanomaterials with disordered, ramified structure are increasingly being used for applications where low cost and enhanced performance are desired. A particular example is the use in printed electronics of inorganic conducting and semiconducting nanoparticles. The electrical, as well as other physical properties depend on the arrangement and connectivity of the particles in such aggregate systems. Quantification of aggregate structure and development of structure/property relationships is difficult and progress in the application of these materials in electronics has mainly been empirical. In this paper, a scaling model is used to parameterize the structure of printed electronic layers. This model has chiefly been applied to polymers but surprisingly it shows applicability to these nanolayers. Disordered structures of silicon nanoparticles forming aggregates are investigated using small angle x-ray scattering coupled with the scaling model. It is expected that predictions using these structural parameters can be made for electrical properties. The approach may have wide use in understanding and designing nano-aggregates for electronic devices.

  11. 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: Frode.Selheim@biomed.uib.no [Proteomic Unit at University of Bergen (PROBE), University of Bergen, Bergen (Norway); Department of Biomedicine, University of Bergen, Bergen (Norway)

    2014-07-04

    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.

  12. [Platelet aggregation upon acetylsalicylic acid and clopidogrel treatment and glycoprotein IIb/IIIa content in patients with acute coronary syndrome].

    Science.gov (United States)

    Khaspekova, S G; Ziuriaev, I T; Iakushkin, V V; Golubeva, N V; Ruda, M Ia; Mazurov, A V

    2011-01-01

    Interaction between aggregating activity of platelets and glycoprotein (GP) IIb/IIIa (fibrinogen receptor) content on their surface was investigated in patients with acute coronary syndrome (ACS). Eighty nine ACS patients were included into the study - 69 with and 20 without elevation of ST segment. Blood was collected within the first hour of admission to the clinic (1 day), and then at 3-5 and 8-12 days. All patients received standard antiaggregant therapy - acetylsalicylic acid - ASA (thromboxane A2 synthesis inhibitor) and clopidogrel (ADP receptor antagonist). Platelet aggregation was analyzed at the first time point when patients had already taken ASA but not clopidogrel, and then (3-5 and 8- 12 days) upon combined therapy with both preparations. Aggregation was induced by 5 and 20 uM ADP and measured by turbidimetric method. In comparison with the initial level (1 day, ASA) at days 3-5, i.e. after development of clopidogrel effect, platelet aggregation was decreased by 54 and 40% upon its stimulation with 5 and 20 uM ADP, and was not further changed at days 8-12. GP IIb/IIIa content on platelet surface was determined by binding of 125I-labelled monoclonal antibody CRC64. GP IIb/IIIa number varied from 31100 to 73000 per platelet with the mean level of 48500 +/- 8400 (mean +/- standard deviation). No differences were detected between mean GP IIb/IIIa number at 1, 3-5 and 8-12 days after ACS onset. Upon repeat GP IIb/IIIa measurement coefficient of variation was 6.1% demonstrating the stability of this parameter in each patient. Positive correlation between platelet aggregation and GP IIb/IIIa content was detected at the first day - correlation coefficients (r) 0.425 and 0.470 for 5 and 20 uM ADP (n=57, p0.05). These results indicates that variations of GP IIb/IIIa content affect platelet aggregating activity within first hours of ACS upon ASA treatment. However after saturation with clopidogrel this factor has no significant influence on platelet aggregation

  13. Development of a New Method for Platelet Function Test and Its Shearing Condition in Microfludic System

    Science.gov (United States)

    Lee, Hoyoon; Kim, Gyehyu; Choi, Seawhan; Shin, Sehyun; Korea University Department of Mechanical Engineering Team

    2015-11-01

    Platelet is a crucial blood cell on hemostasis. As platelet exposed to high shear stress, it can be activated showing morphological and functional changes to stop bleeding. When platelet is abnormal, there is high risk of cardiovascular diseases. Thus, quick and precise assay for platelet function is important in clinical treatment. In this study, we design a microfluidic system, which can test platelet function exposed with the stimulation of shear and agonists. The microfluidic system consists of three parts: 1) a shear mechanism with rotating stirrer; 2) multiple microchannels to flow samples and to stop; 3) camera-interfaced migration distance(MD) analyzing system. When sheared blood is driven by pressure through the microchannel, shear-activated platelets adhere to a collagen-coated surface, causing blood flow to significantly slow and eventually stop. As the micro-stirrer speed increases, MD decreases exponentially at first, but it increases beyond a critical rpm after all. These results are coincident with data measured by FACS flowcytometry. These results imply that the present system could quantitatively measure the degree of activation, aggregation and adhesion of platelets and that blood MD is potent index for measuring the shear-dependence of platelet function.

  14. Hemolytic activity and platelet aggregation inhibitory effect of vipoxin's basic sPLA2 subunit

    Science.gov (United States)

    Goranova, Yana; Pantcheva, Ivayla; Atanasov, Vasil; Danchev, Dobri; Petrova, Svetla

    2013-01-01

    In the present study we evaluated the effect of secreted phospholipase A2 (sPLA2) (the toxic subunit of the heterodimeric neurotoxin vipoxin, isolated from the Bulgarian long-nosed viper Vipera ammodytes meridionalis) on hemolysis, erythrocyte morphology and platelet aggregation. Hemolytic activity of sPLA2 was examined in the presence of saturated (palmitic) and unsaturated (oleic) fatty acids and it was found that oleic acid increased the hemolytic activity of sPLA2 in a concentration-dependent manner, compared to the effect of palmitic acid and controls. The addition of heparin to red blood cells (RBC) suspension containing sPLA2 or mixture of sPLA2 and the corresponding fatty acid led to an inhibition of hemolytic activity. The effect of sPLA2 on RBC morphology resulted in formation of echinocytes (spherocyte subtype), suggesting that RBC could be the possible targets attacked by sPLA2. Vipoxin sPLA2 inhibited (in a dose-dependent manner) platelet aggregation when arachidonic acid and collagen were used as inducers, while in the case of ADP its inhibitory effect was inappreciable. PMID:24678250

  15. New analogues of 13-hydroxyocatdecadienoic acid and 12-hydroxyeicosatetraenoic acid block human blood platelet aggregation and cyclooxygenase-1 activity

    Directory of Open Access Journals (Sweden)

    Hirz Taghreed

    2012-12-01

    Full Text Available Abstract Background Thromboxane A2 is derived from arachidonic acid through the action of cyclooxygenases and thromboxane synthase. It is mainly formed in blood platelets upon activation and plays an important role in aggregation. Aspirin is effective in reducing the incidence of complications following acute coronary syndrome and stroke. The anti-thrombotic effect of aspirin is obtained through the irreversible inhibition of cyclooxygenases. Analogues of 12-hydroxyeicosatetraenoic acid and 13-hydroxyocatdecadienoic acid were shown previously to modulate platelet activation and to block thromboxane receptors. Results and discussion We synthesized 10 compounds based on the structures of analogues of 12-hydroxyeicosatetraenoic acid and 13-hydroxyocatdecadienoic acid and evaluated their effect on platelet aggregation triggered by arachidonic acid. The structure activity relationship was evaluated. Five compounds showed a significant inhibition of platelet aggregation and highlighted the importance of the lipidic hydrophobic hydrocarbon chain and the phenol group. Their IC50 ranged from 7.5 ± 0.8 to 14.2 ± 5.7 μM (Mean ± S.E.M.. All five compounds decreased platelet aggregation and thromboxane synthesis in response to collagen whereas no modification of platelet aggregation in response to thromboxane receptor agonist, U46619, was observed. Using COS-7 cells overexpressing human cyclooxygenase-1, we showed that these compounds are specific inhibitors of cyclooxygenase-1 with IC50 ranging from 1.3 to 12 μM. Docking observation of human recombinant cyclooxygenase-1 supported a role of the phenol group in the fitting of cyclooxygenase-1, most likely related to hydrogen bonding with the Tyr 355 of cyclooxygenase-1. Conclusions In conclusion, the compounds we synthesized at first based on the structures of analogues of 12 lipoxygenase metabolites showed a role of the phenol group in the anti-platelet and anti-cyclooxygenase-1 activities

  16. Ehlers-danlos syndrome with platelet aggregation defect-presenting as mysterious bleeding disorder

    Directory of Open Access Journals (Sweden)

    Sawhney M

    2003-01-01

    Full Text Available A 7-year-old girl presented with recurrent episodes of petechiae, purpura and ecchymoses since six months of age and recurrent episodes of mild to severe epistaxis since two years of age requiring repeated blood transfusions. In April '99 while being investigated for a massive epistaxis, she was found to have platelet function defect with abnormal aggregation of platelets to ADP, epinephrine, collagen as well as to ristocetin. Further investigations ruled out the possibility of Glanzmann's disorder and von-Willebrand's disease as to its cause. In May 2001 she was referred to the dermatologist for evaluation of subcutaneous tumours, which had developed since the last six months. On clinical evaluation, she was found to be having mild hyperextensibility of the skin, joint hypermobility, atrophic scars over knee, spontaneous bruises over right forearm and left thigh and nontender firm to hard subcutaneous nodules over both wrists, both shoulders, right index finger and dorsum of right foot consistent with a clinical picture of a mild form of Ehlers-Danlos syndrome (EDS. Histopathology of the nodule from left wrist was consistent with molluscoid tumour of EDS and skin histopathology and ultrastructure studies showed thick irregular collagen fibrils. Only other sibling, a five-year-old male also had history of repeated mild to moderate epistaxis and on examination was found to have a milder variant of EDS. Born out of I degree consanguineous marriage of normal parents with mildly affected other sibling, she was diagnosed to be suffering from EDS with autosomal recessive inheritance, most probably EDS type X due to the associated platelet aggregation defect. Only one such family with EDS type X has been reported so far.

  17. Ehlers-danlos syndrome with platelet aggregation defect-presenting as mysterious bleeding disorder

    Directory of Open Access Journals (Sweden)

    Sawhney M

    2003-03-01

    Full Text Available A 7-year-old girl presented with recurrent episodes of petechiae, purpura and ecchymoses since six months of age and recurrent episodes of mild to severe epistaxis since two years of age requiring repeated blood transfusions. In April '99 while being investigated for a massive epistaxis, she was found to have platelet function defect with abnormal aggregation of platelets to ADP, epinephrine, collagen as well as to ristocetin. Further investigations ruled out the possibility of Glanzmann's disorder and von-Willebrand's disease as to its cause. In May 2001 she was referred to the dermatologist for evaluation of subcutaneous tumours, which had developed since the last six months. On clinical evaluation, she was found to be having mild hyperextensibility of the skin, joint hypermobility, atrophic scars over knee, spontaneous bruises over right forearm and left thigh and nontender firm to hard subcutaneous nodules over both wrists, both shoulders, right index finger and dorsum of right foot consistent with a clinical picture of a mild form of Ehlers-Danlos syndrome (EDS. Histopathology of the nodule from left wrist was consistent with molluscoid tumour of EDS and skin histopathology and ultrastructure studies showed thick irregular collagen fibrils. Only other sibling, a five-year-old male also had history of repeated mild to moderate epistaxis and on examination was found to have a milder variant of EDS. Born out of I degree consanguineous marriage of normal parents with mildly affected other sibling, she was diagnosed to be suffering from EDS with autosomal recessive inheritance, most probably EDS type X due to the associated platelet aggregation defect. Only one such family with EDS type X has been reported so far.

  18. Decreased threshold of aggregation to low-dose epinephrine is evidence of platelet hyperaggregability in patients with thrombosis

    Directory of Open Access Journals (Sweden)

    Chelsea Hayes

    2014-08-01

    Full Text Available Sticky platelet syndrome has been described as a hereditary thrombophilic condition. The aim of this study is to identify the presence of platelet hyperaggregability in patients who have experienced thrombosis. Light-transmittance platelet aggregometry was used to assess for spontaneous platelet aggregation, aggregation in response to full and low-dose (LD epinephrine (Epi and adenosine diphosphate, as well as arachidonic acid, and identify a distinct pattern of platelet hyperaggregability. Light-transmittance platelet aggregometry results were correlated with PFA-100® (Dade-Behring, Marburg, Germany results, when available. An exaggerated response to LD Epi was found in 68% of patients with thrombosis compared to only 36% of healthy controls (P=0.034. Patients with thrombosis, either arterial or venous, demonstrated an exaggerated response to LD Epi nearly twice as frequently as healthy controls, even without significant family history of thrombophilia or other known risk factors for thrombosis. This suggests that platelet hyperaggregability may be multifactorial in nature and not necessarily hereditary.

  19. Purification and Characterization of BmooAi: A New Toxin from Bothrops moojeni Snake Venom That Inhibits Platelet Aggregation

    Directory of Open Access Journals (Sweden)

    Mayara Ribeiro de Queiroz

    2014-01-01

    Full Text Available In this paper, we describe the purification/characterization of BmooAi, a new toxin from Bothrops moojeni that inhibits platelet aggregation. The purification of BmooAi was carried out through three chromatographic steps (ion-exchange on a DEAE-Sephacel column, molecular exclusion on a Sephadex G-75 column, and reverse-phase HPLC chromatography on a C2/C18 column. BmooAi was homogeneous by SDS-PAGE and shown to be a single-chain protein of 15,000 Da. BmooAi was analysed by MALDI-TOF Spectrometry and revealed two major components with molecular masses 7824.4 and 7409.2 as well as a trace of protein with a molecular mass of 15,237.4 Da. Sequencing of BmooAi by Edman degradation showed two amino acid sequences: IRDFDPLTNAPENTA and ETEEGAEEGTQ, which revealed no homology to any known toxin from snake venom. BmooAi showed a rather specific inhibitory effect on platelet aggregation induced by collagen, adenosine diphosphate, or epinephrine in human platelet-rich plasma in a dose-dependent manner, whereas it had little or no effect on platelet aggregation induced by ristocetin. The effect on platelet aggregation induced by BmooAi remained active even when heated to 100°C. BmooAi could be of medical interest as a new tool for the development of novel therapeutic agents for the prevention and treatment of thrombotic disorders.

  20. Inhibitory effects and mechanisms of high molecular-weight phlorotannins from Sargassum thunbergii on ADP-induced platelet aggregation

    Institute of Scientific and Technical Information of China (English)

    WEI Yuxi; WANG Changyun; LI Jing; GUO Qi; QI Hongtao

    2009-01-01

    We evaluated the effects of high molecular-weight phlorotannins from Sargassum thunbergii (STP) on ADP-induced platelet aggregation and arachidonic acid (AA) metabolism in New Zealand white rabbits and Wistar rats. The inhibition of STP on platelet aggregation was investigated using a turbidimetric method, and the levels of the terminal products of AA metabolism were measured using the corresponding kits for maleic dialdehyde (MDA), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) by colorimetry and radioimmunoassay, as appropriate. We found that STP could inhibit ADP-induced platelet aggregation, and the inhibitory ratio was 91.50% at the STP concentration of 4.0 mg/mL. Furthermore, STP markedly affected AA metabolism by decreasing the synthesis of MDA (P<0.01) and increasing the synthesis of 6-keto-PGF1α, thus changing the plasma TXB2/6-keto-PGF1α balance when the platelets were activated (P<0.01). Therefore, STP altered AA metabolism and these findings partly revealed the molecular mechanism by which STP inhibits ADP-induced platelet aggregation.

  1. Dengue fever activates the L-arginine-nitric oxide pathway: an explanation for reduced aggregation of human platelets.

    Science.gov (United States)

    Mendes-Ribeiro, Antonio C; Moss, Monique B; Siqueira, Mariana As; Moraes, Thalyta L; Ellory, J Clive; Mann, Giovanni E; Brunini, Tatiana Mc

    2008-10-01

    In patients with Dengue fever, a viral inflammatory syndrome, haemorrhage is a significant pathological feature, yet the underlying mechanisms remain unclear. Nitric oxide (NO) is an important regulator of platelet function, inhibiting aggregation, recruitment and adhesion to the vascular endothelium. We have investigated whether changes in the activity of the L-arginine-NO pathway in human platelets may account for increased bleeding in patients with Dengue fever. A total of 16 patients with Dengue fever and 18 age-matched healthy volunteers participated in the study. Collagen induced platelet aggregation in a dose-dependent manner in both Dengue patients and controls, but the degree of platelet aggregation was significantly reduced in the patient group. Elevated rates of L-arginine transport in Dengue fever patients were associated with enhanced NO synthase activity and elevated plasma fibrinogen levels. The present study provides the first evidence that Dengue fever is associated with increased L-arginine transport and NO generation and reduced platelet aggregation.

  2. Platelets

    Science.gov (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 ...

  3. Platelet aggregation responses and virus isolation from platelets in calves experimentally infected with type I or type II bovine viral diarrhea virus.

    Science.gov (United States)

    Walz, P H; Bell, T G; Grooms, D L; Kaiser, L; Maes, R K; Baker, J C

    2001-10-01

    Altered platelet function has been reported in calves experimentally infected with type II bovine viral diarrhea virus (BVDV). The purpose of the present study was to further evaluate the ability of BVDV isolates to alter platelet function and to examine for the presence of a virus-platelet interaction during BVDV infection. Colostrum-deprived Holstein calves were obtained immediately after birth, housed in isolation, and assigned to 1 of 4 groups (1 control and 3 treatment groups). Control calves (n = 4) were sham inoculated, while calves in the infected groups (n = 4 for each group) were inoculated by intranasal instillation with 10(7) TCID50 of either BVDV 890 (type II), BVDV 7937 (type II), or BVDV TGAN (type I). Whole blood was collected prior to inoculation (day 0) and on days 4, 6, 8, 10, and 12 after inoculation for platelet function testing by optical aggregometry by using adenosine diphosphate and platelet activating factor. The maximum percentage aggregation and the slope of the aggregation curve decreased over time in BVDV-infected calves; however, statistically significant differences (Freidman repeated measures ANOVA on ranks, P infected with the type II BVDV isolates. Bovine viral diarrhea virus was not isolated from control calves, but was isolated from all calves infected with both type II BVDV isolates from days 4 through 12 after inoculation. In calves infected with type I BVDV, virus was isolated from 1 of 4 calves on days 4 and 12 after inoculation and from all calves on days 6 and 8 after inoculation. Altered platelet function was observed in calves infected with both type II BVDV isolates, but was not observed in calves infected with type I BVDV. Altered platelet function may be important as a difference in virulence between type I and type II BVDV infection.

  4. Effects of aspirin dosage and time of administration on arterial prostacyclin production and platelet aggregation in rats.

    Science.gov (United States)

    Philp, R B; Paul, M L

    1984-07-01

    Previously we reported that electrically-induced carotid artery thrombosis in anesthetized rats was prevented by 3.3 or 10 mg/kg aspirin (ASA) given i.v. 10 min before injury but not by 1.7, 20 or 100 mg/kg and protection was lost by delaying injury to 20 min (Haemostasis 13:42, 1983). Here, collagen-induced platelet aggregation and arterial prostacyclin-generating activity, measured by RIA for 6 keto-PGF1 alpha and by human platelet aggregation bioassay, were studied ex vivo after i.v. ASA to anesthetized rats. In all cases where platelet aggregation was inhibited less than 50%, no protection had been observed (1.7 mg/kg at 10 min, 3.3 at 20 min, 20 at 10 min). In the two cases where protection had been observed, platelet aggregation was inhibited by about 75% or more and in one, prostacyclin activity was about 50% of normal (3.3 mg/kg at 10 min). Thus in five of six dose-time combinations tested, antithrombotic protection could be explained by a requirement for about 50% of normal prostacyclin activity and about 75% of inhibition of collagen aggregation. Aberrant findings are discussed in the light of knowledge of salicylate/aspirin competition for cyclooxygenase.

  5. The effect of physical exercise on the daily rhythm of platelet aggregation and body temperature in horses.

    Science.gov (United States)

    Piccione, Giuseppe; Grasso, Fortunata; Fazio, Francesco; Giudice, Elisabetta

    2008-05-01

    The goal of this study was to investigate the influence of physical activity on the daily rhythm of platelet aggregation and body temperature in horses. Blood samples from 12 Thoroughbred horses, six sedentary animals and six athletes (studied both before and after a period of inactivity) were collected at 4h intervals for 48h via an intravenous cannula inserted into the jugular vein. Body temperature was recorded every 4h for 48h with a rectal probe. Platelet aggregation was measured with an aggregometer. Collagen was used to test the aggregation of the plasma samples. Statistical analysis of the data was performed by one-way repeated-measures analysis of variance (ANOVA) and by single cosinor method. Cosinor analysis identified the periodic parameters and their acrophases (expressed in hours) during the 2 days of monitoring. On each single day, there was a highly significant effect of time in all the horses, with P values Temperature rhythms were unaffected by exercise. Platelet aggregation in exercising horses differed from the sedentary horses, and this difference disappeared after a 2-week period of rest. The results could be interpreted as indicating that physical exercise has an influence on the daily rhythm of platelet aggregation in horses.

  6. An inhibitor selective for collagen-stimulated platelet aggregation from the salivary glands of hard tick Haemaphysalis longicornis and its mechanism of action

    Institute of Scientific and Technical Information of China (English)

    程远国; 吴厚永; 李德昌

    1999-01-01

    Soluble materials of salivary glands from Haemaphysalis longicornis were found to inhibit collagen, ADP, and thrombin-stimulated platelet aggregation. One inhibitory component was purified to salivary gland homogeneity by a combination of gel filtration, ion-exchange, and C8 reverse phase HPLC. The purified activity, named longieornin, is a protein of moleeular weight 16 000 on SDS-PAGE under both reduced and nonredueed conditions. Collagen-mediated aggregation of platelets in plasma and of washed platelets (IC50 was approximately 60 nmol/L) was inhibited with the same efficacy. No inhibition of aggregation stimulated by other effeetors, including ADP, arachidonic acid, thrombin, ristocetin, calcium ionophore A23187, thromboxane A2 mimetic U46619 and 12-O-phorbol-13-myristate acetate, was observed. Longieonin had no effect on platelet adhension to collagen. Not only platelet aggregation but also release reaction, and increase of intraeellar Ca2+ level of platelets in response to collagen were com

  7. Effect of Desmopressin on Platelet Aggregation and Blood Loss in Patients Undergoing Valvular Heart Surgery

    Institute of Scientific and Technical Information of China (English)

    Lei Jin; Hong-Wen Ji

    2015-01-01

    Background:Blood loss after cardiac surgery can be caused by impaired platelet (PLT) function after cardiopulmonary bypass.Desmopressin or 1-deamino-8-D-arginine vasopressin (DDAVP) is a synthetic analog of vasopressin.DDAVP can increase the level of von Willebrand factor and coagulation factor Ⅷ,thus it may enhance PLT function and improve coagulation.In this study,we assessed the effects of DDAVP on PLT aggregation and blood loss in patients undergoing cardiac surgery.Methods:A total of 102 patients undergoing valvular heart surgery (from October 2010 to June 2011) were divided into DDAVP group (n =52) and control group (n =50).A dose of DDAVP (0.3 μtg/kg) was administered to the patients intravenously when they were being re-warmed.At the same time,an equal volume of saline was given to the patients in the control group.PLT aggregation rate was measured with the AggRAM four-way PLT aggregation measurement instrument.The blood loss and transfusion,hemoglobin levels,PLT counts,and urine outputs at different time were recorded and compared.Results:The postoperative blood loss in the first 6 h was significantly reduced in DDAVP group (202 ± 119 ml vs.258 ± 143 ml,P =0.023).The incidence of fresh frozen plasma (FFP) transfusion was decreased postoperatively in DDAVP group (3.8% vs.12%,P =0.015).There was no significant difference in the PLT aggregation,urine volumes,red blood cell transfusions and blood loss after 24 h between two groups.Conclusions:A single dose of DDAVP can reduce the first 6 h blood loss and FFP transfusion postoperatively in patients undergoing valvular heart surgery,but has no effect on PLT aggregation.

  8. Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin

    Science.gov (United States)

    Konstantopoulos, K.; Neelamegham, S.; Burns, A. R.; Hentzen, E.; Kansas, G. S.; Snapp, K. R.; Berg, E. L.; Hellums, J. D.; Smith, C. W.; McIntire, L. V.; Simon, S. I.

    1998-01-01

    BACKGROUND: After activation, platelets adhere to neutrophils via P-selectin and beta2-integrin. The molecular mechanisms and adhesion events in whole blood exposed to venous levels of hydrodynamic shear in the absence of exogenous activation remain unknown. METHODS AND RESULTS: Whole blood was sheared at approximately 100 s(-1). The kinetics of neutrophil-platelet adhesion and neutrophil aggregation were measured in real time by flow cytometry. P-selectin was upregulated to the platelet surface in response to shear and was the primary factor mediating neutrophil-platelet adhesion. The extent of neutrophil aggregation increased linearly with platelet adhesion to neutrophils. Blocking either P-selectin, its glycoprotein ligand PSGL-1, or both simultaneously by preincubation with a monoclonal antibody resulted in equivalent inhibition of neutrophil-platelet adhesion (approximately 30%) and neutrophil aggregation (approximately 70%). The residual amount of neutrophil adhesion was blocked with anti-CD11b/CD18. Treatment of blood with prostacyclin analogue ZK36374, which raises cAMP levels in platelets, blocked P-selectin upregulation and neutrophil aggregation to baseline. Complete abrogation of platelet-neutrophil adhesion required both ZK36374 and anti-CD18. Electron microscopic observations of fixed blood specimens revealed that platelets augmented neutrophil aggregation both by forming bridges between neutrophils and through contact-mediated activation. CONCLUSIONS: The results are consistent with a model in which venous levels of shear support platelet adherence to neutrophils via P-selectin binding PSGL-1. This interaction alone is sufficient to mediate neutrophil aggregation. Abrogation of platelet adhesion and aggregation requires blocking Mac-1 in addition to PSGL-1 or P-selectin. The described mechanisms are likely of key importance in the pathogenesis and progression of thrombotic disorders that are exacerbated by leukocyte-platelet aggregation.

  9. The contribution of platelets to the pathogenesis of Raynaud's phenomenon and systemic sclerosis.

    Science.gov (United States)

    Pauling, J D; O'Donnell, V B; Mchugh, N J

    2013-01-01

    Raynaud's phenomenon (RP) describes the excessive vascular response of the digital vessels in response to cold exposure and emotional stress. It is typically the earliest manifestation of systemic sclerosis (SSc), a multisystem disease of unknown aetiology characterised by vasculopathy, inflammation and fibrosis. The biological actions of platelets are known to extend beyond primary haemostasis with a growing appreciation of their contribution to vascular function, inflammation and wound repair. This has led to a considerable body of work evaluating associations between platelet function analysis and RP/SSc. This review provides a conceptual framework upon which the potential contribution of platelets to vascular dysfunction, autoimmunity and tissue remodelling in RP and SSc is considered. We describe the existing evidence to support excessive platelet activation in RP and SSc, ranging from the early studies of platelet aggregability and circulating platelet-derived mediators, to the important findings of the recent work that has begun to explore the potential direct pathogenic role of platelets in established murine models of SSc. We shall describe and critically appraise the findings of previous therapeutic studies evaluating the use of anti-platelet agents in RP and SSc, along with their implications for future therapeutic intervention in these conditions.

  10. Extract from Aronia melanocarpa fruits potentiates the inhibition of platelet aggregation in the presence of endothelial cells

    Science.gov (United States)

    Luzak, Boguslawa; Golanski, Jacek; Rozalski, Marek; Krajewska, Urszula; Olas, Beata

    2010-01-01

    Introduction Some polyphenolic compounds extracted from Aronia melanocarpa fruits (AM) have been reported to be cardioprotective agents. In this study we evaluated the ability of AM extract to increase the efficacy of human umbilical vein endothelial cells (HUVECs) to inhibit platelet functions in vitro. Material and methods This study encompasses two models of monitoring platelet reactivity: optical aggregation and platelet degranulation (monitored as the surface CD62P expression) in PRP upon the stimulation with ADP. Results We observed that only at low concentrations (5 µg/ml) did AM extract significantly improve antiplatelet action of HUVECs towards ADP-activated platelets in the aggregation test. Conclusions It is concluded that the potentiating effect of AM extract on the endothelial cell-mediated inhibition of platelet aggregation clearly depends on the used concentrations of Aronia-derived active compounds. Therefore, despite these encouraging preliminary outcomes on the beneficial effects of AM extract polyphenols, more profound dose-effect studies should certainly be considered before the implementation of Aronia-originating compounds in antiplatelet therapy and the prevention of cardiovascular diseases. PMID:22371737

  11. Vascular pentraxin 3 controls arterial thrombosis by targeting collagen and fibrinogen induced platelets aggregation

    Science.gov (United States)

    Bonacina, F.; Barbieri, S.S.; Cutuli, L.; Amadio, P.; Doni, A.; Sironi, M.; Tartari, S.; Mantovani, A.; Bottazzi, B.; Garlanda, C.; Tremoli, E.; Catapano, A.L.; Norata, G.D.

    2016-01-01

    Aim The long pentraxin PTX3 plays a non-redundant role during acute myocardial infarction, atherosclerosis and in the orchestration of tissue repair and remodeling during vascular injury, clotting and fibrin deposition. The aim of this work is to investigate the molecular mechanisms underlying the protective role of PTX3 during arterial thrombosis. Methods and results PTX3 KO mice transplanted with bone marrow from WT or PTX3 KO mice presented a significant reduction in carotid artery blood flow following FeCl3 induced arterial thrombosis (− 80.36 ± 11.5% and − 95.53 ± 4.46%), while in WT mice transplanted with bone marrow from either WT or PTX3 KO mice, the reduction was less dramatic (− 45.55 ± 1.37% and − 53.39 ± 9.8%), thus pointing to a protective effect independent of a hematopoietic cell's derived PTX3. By using P-selectin/PTX3 double KO mice, we further excluded a role for P-selectin, a target of PTX3 released by neutrophils, in vascular protection played by PTX3. In agreement with a minor role for hematopoietic cell-derived PTX3, platelet activation (assessed by flow cytometric expression of markers of platelet activation) was similar in PTX3 KO and WT mice as were haemostatic properties. Histological analysis indicated that PTX3 localizes within the thrombus and the vessel wall, and specific experiments with the N-terminal and the C-terminal PTX3 domain showed the ability of PTX3 to selectively dampen either fibrinogen or collagen induced platelet adhesion and aggregation. Conclusion PTX3 interacts with fibrinogen and collagen and, by dampening their pro-thrombotic effects, plays a protective role during arterial thrombosis. PMID:26976330

  12. Prolongation of bleeding time and inhibition of platelet aggregation by low-dose acetylsalicylic acid in patients with cerebrovascular disease

    DEFF Research Database (Denmark)

    Boysen, G; Boss, A H; Ødum, Niels

    1984-01-01

    Platelet aggregation and bleeding time was measured in 43 cerebrovascular patients participating in a controlled double-blind study of low-dose acetylsalicylic acid. In 19 patients with satisfactory inhibition of the platelet aggregation obtained by 50 to 70 mg acetylsalicylic acid per day...... the bleeding time averaged 11.2 minutes in contrast to 7.0 minutes in the placebo group, p less than 0.001. This study confirms our previous findings of platelet inhibition by low-dose acetylsalicylic acid in patients with cerebrovascular disease. The prolongation of the bleeding time demonstrates that we...... are dealing not merely with an in vitro phenomenon but with a significant in vivo effect. The study provides the rationale for clinical evaluations of low-dose acetylsalicylic acid in stroke prophylaxis....

  13. The human endogenous circadian system causes greatest platelet activation during the biological morning independent of behaviors.

    Directory of Open Access Journals (Sweden)

    Frank A J L Scheer

    Full Text Available BACKGROUND: Platelets are involved in the thromboses that are central to myocardial infarctions and ischemic strokes. Such adverse cardiovascular events have day/night patterns with peaks in the morning (~9 AM, potentially related to endogenous circadian clock control of platelet activation. The objective was to test if the human endogenous circadian system influences (1 platelet function and (2 platelet response to standardized behavioral stressors. We also aimed to compare the magnitude of any effects on platelet function caused by the circadian system with that caused by varied standardized behavioral stressors, including mental arithmetic, passive postural tilt and mild cycling exercise. METHODOLOGY/PRINCIPAL FINDINGS: We studied 12 healthy adults (6 female who lived in individual laboratory suites in dim light for 240 h, with all behaviors scheduled on a 20-h recurring cycle to permit assessment of endogenous circadian function independent from environmental and behavioral effects including the sleep/wake cycle. Circadian phase was assessed from core body temperature. There were highly significant endogenous circadian rhythms in platelet surface activated glycoprotein (GP IIb-IIIa, GPIb and P-selectin (6-17% peak-trough amplitudes; p ≤ 0.01. These circadian peaks occurred at a circadian phase corresponding to 8-9 AM. Platelet count, ATP release, aggregability, and plasma epinephrine also had significant circadian rhythms but with later peaks (corresponding to 3-8 PM. The circadian effects on the platelet activation markers were always larger than that of any of the three behavioral stressors. CONCLUSIONS/SIGNIFICANCE: These data demonstrate robust effects of the endogenous circadian system on platelet activation in humans--independent of the sleep/wake cycle, other behavioral influences and the environment. The 9 AM timing of the circadian peaks of the three platelet surface markers, including platelet surface activated GPIIb-IIIa, the

  14. Tripeptide SQL Inhibits Platelet Aggregation and Thrombus Formation by Affecting PI3K/Akt Signaling.

    Science.gov (United States)

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

    2015-09-01

    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.

  15. A novel thromboxane receptor antagonist, nstpbp5185, inhibits platelet aggregation and thrombus formation in animal models.

    Science.gov (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

    2016-08-01

    A novel benzimidazole derivative, nstpbp5185, was discovered through in vitro and in vivo evaluations for antiplatelet activity. Thromaboxane receptor (TP) is important in vascular physiology, haemostasis and pathophysiological thrombosis. Nstpbp5185 concentration-dependently inhibited human platelet aggregation caused by collagen, arachidonic acid and U46619. Nstpbp5185 caused a right-shift of the concentration-response curve of U46619 and competitively inhibited the binding of 3H-SQ-29548 to TP receptor expressed on HEK-293 cells, with an IC50 of 0.1 µM, indicating that nstpbp5185 is a TP antagonist. In murine thrombosis models, nstpbp5185 significantly prolonged the latent period in triggering platelet plug formation in mesenteric and FeCl3-induced thrombi formation, and increased the survival rate in pulmonary embolism model with less bleeding than aspirin. This study suggests nstpbp5185, an orally selective anti-thrombotic agent, acting through blockade of TXA2 receptor, may be efficacious for prevention or treatment of pathologic thrombosis.

  16. Celecoxib interferes to a limited extent with aspirin-mediated inhibition of platelets aggregation.

    Science.gov (United States)

    Ruzov, Mark; Rimon, Gilad; Pikovsky, Oleg; Stepensky, David

    2016-02-01

    The aim of the study was to analyze the interaction between celecoxib and low dose aspirin for COX-1 binding and its consequences on the aspirin-mediated antiplatelet effects. We investigated ex vivo the interaction between celecoxib and aspirin for COX-1 binding and measured the resulting antiplatelet effects. We applied mechanism-based pharmacokinetic-pharmacodynamic (PKPD) modelling to analyze these data and to predict in vivo platelet aggregation for different doses and administration schedules of aspirin and celecoxib. The predictions of the PK-PD model were consistent with results from previous studies that investigated interaction between aspirin and celecoxib. The modelling results indicate that celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. The extent of this interaction can be substantial (up to 15% increase in platelet aggregation by 200 mg day(-1) celecoxib when combined with low dose aspirin) during the first days of aspirin administration in patients who are already treated with celecoxib, and it cannot be prevented by separate administration of the interacting drugs. At the recommended therapeutic doses, celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. Patients receiving a combination of low dose aspirin and the recommended doses of celecoxib were not identified to have increased risk of cardiovascular and cerebrovascular events due to competition between these drugs for COX-1 binding. Interaction between low dose aspirin and other COX-2 inhibitors and its clinical consequences requires further investigation. © 2015 The British Pharmacological Society.

  17. Extracts from Trifolium pallidum and Trifolium scabrum aerial parts as modulators of blood platelet adhesion and aggregation.

    Science.gov (United States)

    Kolodziejczyk-Czepas, Joanna; Olas, Beata; Malinowska, Joanna; Wachowicz, Barbara; Szajwaj, Barbara; Kowalska, Iwona; Oleszek, Wieslaw; Stochmal, Anna

    2013-01-01

    A growing number of reports indicate that some species of clover (Trifolium) may have remarkable medical importance; however, the effects of these plants on blood platelets and hemostasis are inadequately recognized. This work was designed to study the effects of Trifolium pallidum and Trifolium scabrum extracts on the functions of human blood platelets in vitro. Platelet suspensions were preincubated with extracts from aerial parts of T. pallidum (phenolic fraction and clovamide fraction) and T. scabrum (phenolic fraction) at the final concentrations of 12.5, 25, and 50 µg/ml. Then, for platelet activation thrombin (0.1 U/ml), thrombin receptor activating peptide (TRAP; 20 µM), or adenosine diphosphate (ADP; 1 µM) were used. The effects of Trifolium extracts on adhesion of blood platelets to fibrinogen and collagen were determined by enzyme-linked immunosorbent assay (ELISA) method. Platelet aggregation was monitored on a dual-channel Chronolog aggregometer. In these studies, we also compared the action of tested plant extracts with the effects of another antiplatelet plant-derived compound - resveratrol (3,4',5-trihydroxystilbene). The performed assays demonstrated that the tested extracts might influence the platelet functions in vitro. The inhibitory, concentration-dependent effects of all tested extracts on adhesion of thrombin-stimulated platelets to collagen was found. Both extracts from T. pallidum and from T. scabrum reduced the thrombin-induced platelet adhesion to fibrinogen. Furthermore, in the presence of all three extracts, the platelet aggregation induced by thrombin was slightly inhibited. Our results also indicate that the tested plant extracts (at the highest concentrations used of 50 µg/ml), similar to purified resveratrol, inhibit selected steps of platelet activation stimulated by both proteolytic (thrombin) and nonproteolytic agonists (TRAP or ADP). In the comparative studies, T. pallidum and T. scabrum extracts was not found

  18. Platelets as delivery systems for disease treatments

    OpenAIRE

    Shi, Qizhen; Montgomery, Robert R.

    2010-01-01

    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...

  19. Anti-Platelet Aggregation and Vasorelaxing Effects of the Constituents of the Rhizomes of Zingiber officinale

    Directory of Open Access Journals (Sweden)

    Tian-Shung Wu

    2012-07-01

    Full Text Available In the present study, the chemical investigation of the bioactive fractions of the rhizomes of Zingiber officinale has resulted in the identification of twenty-nine compounds including one new compound, O-methyldehydrogingerol (1. Some of the isolates were subjected into the evaluation of their antiplatelet aggregation and vasorelaxing bioactivities. Among the tested compounds, [6]-gingerol (13 and [6]-shogaol (17 exhibited potent anti-platelet aggregation bioactivity. In addition, [10]-gingerol (15 inhibited the Ca2+-dependent contractions in high K+ medium. According to the results in the present research, the bioactivity of ginger could be related to the anti-platelet aggregation and vasorelaxing mechanism.

  20. Platelet adhesiveness and aggregation in congenital afibrinogenemia. An investigation of three patients with post-transfusion, cross-correction studies between two of them.

    Science.gov (United States)

    Girolami, A; De Marco, L; Virgolini, L; Peruffo, R; Fabris, F

    1975-02-01

    Platelet adhesiveness and aggregation were studied in three patients with congenital afibrinogenemia. The results obtained may be summarized as follows: The retention of platelets to a glass-bead filter determined with the Salzman method was significantly decreased; it was normal after fibrinogen infusion. With a modification of the Hellem test the values obtained were slightly decreased. Adrenalin-induced aggregation was absent whereas ADP-and collagen-induced aggregation was near normal or slightly decreased. Thrombofax aggregation was absent in citrated plasma. The abnormalities of platelet aggregation were corrected after fibrinogen infusion or after addition in vitro of fibrinogen, hemofilia A plasma and PPP obtained from an afibrinogenemic patient after fibrinogen infusion. The abnormalities of platelet aggregation were corrected well by ADP, collagen and Thrombofax in heparinized blood, but only a slight correction of adrenalin-induced aggregation was noted. Thrombin aggregation proved to be normal with the higher concentrations, whereas it was defective with the lower ones. Ristocetin aggregation was normal in citrated plasma at the concentration of 1.5 mg per ml but it was absent at the lower concentration (1.0 mg per ml). Ristocetin aggregation was, on the other hand absent in heparinized blood regardless of the concentration. These findings are in agreement with the presence of a prolonged bleeding time in congenital afibrinogenemia and suggest that fibrinogen plays an important role in platelet aggregation and adhesiveness.

  1. The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

    Science.gov (United States)

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

    2016-01-01

    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

  2. Inhibition of collagen-induced platelet aggregation by anopheline antiplatelet protein, a saliva protein from a malaria vector mosquito.

    Science.gov (United States)

    Yoshida, Shigeto; Sudo, Toshiki; Niimi, Masashi; Tao, Lian; Sun, Bing; Kambayashi, Junichi; Watanabe, Hiroyuki; Luo, Enjie; Matsuoka, Hiroyuki

    2008-02-15

    During blood feeding, mosquitoes inject saliva containing a mixture of molecules that inactivate or inhibit various components of the hemostatic response to the bite injury as well as the inflammatory reactions produced by the bite, to facilitate the ingestion of blood. However, the molecular functions of the individual saliva components remain largely unknown. Here, we describe anopheline antiplatelet protein (AAPP) isolated from the saliva of Anopheles stephensi, a human malaria vector mosquito. AAPP exhibited a strong and specific inhibitory activity toward collagen-induced platelet aggregation. The inhibitory mechanism involves direct binding of AAPP to collagen, which blocks platelet adhesion to collagen and inhibits the subsequent increase in intracellular Ca(2+) concentration ([Ca(2+)]i). The binding of AAPP to collagen effectively blocked platelet adhesion via glycoprotein VI (GPVI) and integrin alpha(2)beta(1). Cell adhesion assay showed that AAPP inhibited the binding of GPVI to collagen type I and III without direct effect on GPVI. Moreover, intravenously administered recombinant AAPP strongly inhibited collagen-induced platelet aggregation ex vivo in rats. In summary, AAPP is a malaria vector mosquito-derived specific antagonist of receptors that mediate the adhesion of platelets to collagen. Our study may provide important insights for elucidating the effects of mosquito blood feeding against host hemostasis.

  3. Targeted deep resequencing identifies coding variants in the PEAR1 gene that play a role in platelet aggregation.

    Directory of Open Access Journals (Sweden)

    Yoonhee Kim

    Full Text Available Platelet aggregation is heritable, and genome-wide association studies have detected strong associations with a common intronic variant of the platelet endothelial aggregation receptor1 (PEAR1 gene both in African American and European American individuals. In this study, we used a sequencing approach to identify additional exonic variants in PEAR1 that may also determine variability in platelet aggregation in the GeneSTAR Study. A 0.3 Mb targeted region on chromosome 1q23.1 including the entire PEAR1 gene was Sanger sequenced in 104 subjects (45% male, 49% African American, age = 52±13 selected on the basis of hyper- and hypo- aggregation across three different agonists (collagen, epinephrine, and adenosine diphosphate. Single-variant and multi-variant burden tests for association were performed. Of the 235 variants identified through sequencing, 61 were novel, and three of these were missense variants. More rare variants (MAF<5% were noted in African Americans compared to European Americans (108 vs. 45. The common intronic GWAS-identified variant (rs12041331 demonstrated the most significant association signal in African Americans (p = 4.020×10(-4; no association was seen for additional exonic variants in this group. In contrast, multi-variant burden tests indicated that exonic variants play a more significant role in European Americans (p = 0.0099 for the collective coding variants compared to p = 0.0565 for intronic variant rs12041331. Imputation of the individual exonic variants in the rest of the GeneSTAR European American cohort (N = 1,965 supports the results noted in the sequenced discovery sample: p = 3.56×10(-4, 2.27×10(-7, 5.20×10(-5 for coding synonymous variant rs56260937 and collagen, epinephrine and adenosine diphosphate induced platelet aggregation, respectively. Sequencing approaches confirm that a common intronic variant has the strongest association with platelet aggregation in African Americans

  4. Effect of Platelet Concentration of Platelet-rich Plasma on Platelet Aggregation%富血小板血浆中血小板浓度对血小板聚集的影响

    Institute of Scientific and Technical Information of China (English)

    李祖兰; 张靓; 杨亮程; 任军伟; 丛玉隆; 夏杰成; 李健; 马长生; 邓新立; 王海立

    2012-01-01

    Objective To explore the effect of platelet concentration of platelet-rich plasma (PEP) on platelet aggregation. Methods 107 blood samples of outpatient volunteers were randomly collected and centrifuged, PRP and PPP( platelet-poor plasma) were gotten , then platelet concentration of PRP was detected by the blood analyzer and diluted with their own PPP into a series of platelet concentration of plasma in the gradient: 50×109/ L ~ 400×109/L, then platelet aggregation rates of the plasma were detected according to the standard protocols by plasma turbidimetry. Results The platelet concentrations of the plasma were in the range of 50×109/L ~ 400 ×109/L, and the platelet aggregation rate gradually increased with a higher concentration of platelet, but slowly at the concentration of 250×109/L. When platelet concentrations 150×109/L at least for routine platelet aggregation tests. The platelet concentration of 250×10 /L seems to be the optimal concentration for platelet aggregation by plasma turbidimetry.%目的 探讨富血小板血浆(PRP)血小板浓度对血小板聚集的影响.方法 随机收集107名门诊体检健康志愿者静脉血浆,分离PRP和PPP(贫血小板血浆)后,用血液分析仪测定PRP血小板浓度,按PRP浓度用自身PPP配成50×109/L ~400×109/L浓度梯度的血浆,用血浆比浊法测血小板聚集率.结果 PRP血小板浓度在50×109/L~400×109/L,二磷酸腺苷(ADP)和花生四烯酸(AA)诱导的血小板聚集率分别为(10.4±8.7)%至(55.3±9.9)%和0%至(75.2±10.1)%,血小板聚集率随血小板浓度的增高而增高,血小板浓度为250×109/L时,聚集率增幅减缓,血小板浓度小于150×109/L时,血小板聚集率明显降低.结论 PRP血小板浓度对血小板聚集的影响明显,血小板聚集试验PRP血小板浓度大于150×109/L;血浆比浊法血小板聚集试验适宜的血小板浓度为250×109/L.

  5. Inhibition of human platelet aggregation by dihydropyrano- and dihydrofuranocoumarins, a new class of cAMP-phosphodiesterase inhibitors

    DEFF Research Database (Denmark)

    Thastrup, Ole; Knudsen, J B; Lemmich, J;

    1985-01-01

    Certain esters of dihydropyranocoumarin and dihydrofuranocoumarin alcohols have previously been shown to inhibit the cAMP-phosphodiesterase from bovine heart. We now report that these naturally occurring coumarins inhibit the high affinity (Km = 1.1 microM) cAMP-phosphodiesterase from human...... platelets with activities that closely correlate with those obtained using phosphodiesterase from bovine heart tissue. Additionally the coumarins inhibit the aggregation of human platelets induced with ADP, adrenaline and collagen with activities comparable to those of dipyridamole. A lack of significant...

  6. Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists.

    Science.gov (United States)

    Khan, Nadia; Farooq, Ahsana Dar; Sadek, Bassem

    2015-01-01

    In the present study, the mechanism(s) of synergistic interaction of various platelet mediators such as arachidonic acid (AA) when combined with 5-hydroxytryptamine (5-HT) or adenosine diphosphate (ADP) on human platelet aggregation were examined. The results demonstrated that 5-HT had no or negligible effect on aggregation but it did potentiate the aggregation response of AA. Similarly, the combination of subeffective concentrations of ADP and AA exhibited noticeable rise in platelet aggregation. Moreover, the observed synergistic effect of AA with 5-HT on platelets was inhibited by different cyclooxygenase (COX) inhibitors, namely ibuprofen and celecoxib, with half maximal inhibitory effect (IC50) values of 18.0 ± 1.8 and 15.6 ± 3.4 μmol/L, respectively. Interestingly, the synergistic effect observed for AA with 5-HT was, also, blocked by the 5-HT receptor blockers cyproheptadine (IC50=22.0 ± 7 μmol/L), ketanserin (IC50=152 ± 23 μmol/L), phospholipase C (PLC) inhibitor (U73122; IC50=6.1 ± 0.8 μmol/L), and mitogen activated protein kinase (MAPK) inhibitor (PD98059; IC50=3.8 ± 0.5 μmol/L). Likewise, the synergism of AA and ADP was, also, attenuated by COX inhibitors (ibuprofen; IC50=20 ± 4 μmol/L and celecoxib; IC50=24 ± 7 μmol/L), PLC inhibitor (U73122; IC50=3.7 ± 0.3 μmol/L), and MAPK inhibitor (PD98059; IC50=2.8 ± 1.1 μmol/L). Our observed data demonstrate that the combination of subthreshold concentrations of agonists amplifies platelet aggregation and that these synergistic effects largely depend on activation of COX/thromboxane A2, receptor-operated Ca(2+) channels, Gq/PLC, and MAPK signaling pathways. Moreover, our data revealed that inhibition of COX pathways by using both selective and/or non-selective COX inhibitors blocks not only AA metabolism and thromboxane A2 formation, but also its binding to Gq receptors and activation of receptor-operated Ca(2+) channels in platelets. Overall, our results show that PLC and MAPK inhibitors proved

  7. Effect of pretreatment with aspirin and ticlopidine on the change of platelet aggregability after radiofrequency catheter ablation

    Institute of Scientific and Technical Information of China (English)

    王利宏; 陈君柱; 郑良荣; 陶谦民

    2002-01-01

    Eighty-two patients with supraventricular tachycardia undergoing radi o frequency catheter ablation (RFCA) were studied to observe the inhibition effect of aspirin and ticlopidine on platelet aggregability (PAG) and thromboxane B2 (T XB2) of the blood samples. Patients were divided into aspirin group A, ticlopi di ne group B, aspirin+ticlopidine group C and control group D. PAG and TXB2 were i ncreased clearly after RFCA in all groups (P<0.001). Treatment with aspirin or t iclopidine before operation could reduce the platelet aggregability caused by RF CA and the joint effect of two drugs(change rate of group A:52.51±12.51%; group B:54.78±11.27%;group C: 30.51±10.59%;group D:91.75±21.43%; P<0.05)was st udie d. The much decreased platelet aggregability after antiplatelet therapy was evid ence of the potential benefit of the treatment in preventing thromboembolism aft er ablation. Pretreatment with aspirin and ticlopidine together is a good way to decrease palatelet aggregability after RFCA.

  8. 血小板数量对血浆比浊法测定血小板聚集率的影响%The Effect of Different Platelet Counts for Plasma Turbidimetry on Platelet Aggregation Rate

    Institute of Scientific and Technical Information of China (English)

    张庆

    2015-01-01

    Objective To investigate the effect of platelet counts on platelet aggregation test,to regulate platelet aggrega-tion rate detection to improve detection quality,in order to ensure the reliability of measurements of platelet aggregation. Meth-ods 211 cases of healthy people venous whole blood samples were included and centrifuged to obtain platelet-rich plasma ( plate-let-rich plasma,PRP) and platelet-poor plasma (platelet-poor plasma,PPP),the PRP with PPP got different dilutions of platelet concentration of PRP samples tested ,concentration of PRP platelet were confirmed in plasma;Platelet aggregation rate was detected by platelet aggregation nephelometry, and discuss the correlation with platelet. Results Adenosine diphosphate ( ADP ) and arachidonic acid( AA) induced platelet aggregation rate within a laboratory setting reference range. with decreasing concentration of platelet,the aggregation rate decreased significantly(P<0. 05);when the concentration was reduced to <95 ×109/L,the aggre-gate rate of the test resulted below the established reference range;platelet 90~350 × 10 9/L was significantly correlation with the accumulation(rAA =0. 67,rADP =0. 69),other concentrations and aggregation had no correlation. Conclusion Platelet concentra-tion can affect platelet aggregation rate,determination of aggregation rate should be limited at above of 95 × 10 9/L,which reflect the relation of concentration and aggregation rate,and accurately reflect the concentration of aggregation.%目的 探讨血小板数量对血小板聚集率检测的影响,提高检测质量,保证聚集率测定结果的可靠性. 方法 收集211例健康人静脉全血标本,离心获取富血小板血浆( platelet-rich plasma,PRP)和乏血小板血浆( platelet-poor plas-ma,PPP) ,将PRP用自身PPP梯度稀释后获取不同血小板浓度的PRP检测样本,并确认PRP血浆中血小板浓度;利用血浆比浊法测定血小板聚集率,讨论血小板数量与血小

  9. Differences between mainstream and sidestream tobacco smoke extracts and nicotine in the activation and aggregation of platelets subjected to cardiovascular conditions in diabetes.

    Science.gov (United States)

    Yin, Wei; Rubenstein, David A

    2013-01-01

    Mainstream and sidestream tobacco smoke extracts have been shown to increase platelet activation directly. Furthermore, advanced glycation end products, which are present in the diabetic vasculature, have also been shown to enhance platelet activity. However, the combined effects of these two risk factors on platelet functions remain unclear. Platelets were exposed to tobacco extracts concurrently with advanced glycation end products. Timed samples were removed to assess the extent of platelet activity. The presence of smoke extracts enhanced platelet activity as compared to control conditions, this was especially prevalent for sidestream extracts. With the addition of irreversibly glycated albumin, there was an additive effect, further enhancing platelet responses. This was at least partially regulated by α-granule release and CD41 expression. The combination of cardiovascular risk factors can significantly enhance platelet activation and aggregation, and therefore it is possible to accelerate cardiovascular diseases through the interactions of multiple cardiovascular risk factors.

  10. [Effect of L-arginine on platelet aggregation, endothelial function adn exercise tolerance in patients with stable angina pectoris].

    Science.gov (United States)

    Sozykin, A V; Noeva, E A; Balakhonova, T V; Pogorelova, O A; Men'shikov, M Iu

    2000-01-01

    Examination of the action of donor NO (L-arginine) on platelet aggregation, endothelial function and exercise tolerance in patients with stable angina of effort (SAE). 42 patients with SAE (functional class I-II) and 10 healthy volunteers (control group) were assigned to two groups. 22 patients of group 1 were randomized to cross-over. They received cardiket (60 mg/day for 10 days or cardiket (60 mg/day) in combination with L-arginine (15 g/day for 10 days). 20 SAE patients of group 2 and control group received L-arginine (15 g/day for 10 days). In each group blood lipids were examined, and bicycle exercise test (BET) was performed. In addition, platelet aggregation and endothelial function were studied in group 2 and control group before and after the course of L-arginine. Compared to control group, endothelial function significantly improved in group 2 (from 5.0 +/- 2.9 to 7.8 +/- 4.1% vs 7.1 +/- 1.9 to 6.6 +/- 4.8%) (M +/- SD). BET duration increased in all the patients. After ADP addition in concentrations 1.5, 2.0, and 5.0 micromol/l platelet aggregation declined in 17 patients except 3 in whom the aggregation remained unchanged. Positive effect of L-arginine on endothelial function, exercise tolerance and platelet aggregation was observed in patients with stable angina of effort (functional class I-II). Therefore, arginine can be recommended as an adjuvant in the treatment of patients with ischemic heart disease.

  11. Specific inhibiting effects of Ilexonin A on von Willebrand factor-dependent platelet aggregation under high shear rate

    Institute of Scientific and Technical Information of China (English)

    李敏; 吴伟康; 刘良; 廖福龙; 篠原幸人; 半田俊之介; 後藤信哉

    2004-01-01

    Background Ilexonin A (IA), purified from the Chinese herbal medicine Maodongqing (Ilex pubescens Hook, et Am) has been commonly used in south China to treat thrombotic disorders. In this study, we aimed to study the inhibiting effects and mechanism of lA on von Willebrand factor (vWF)-dependent high shear-induced platelet aggregation. Methods vWF-dependent high shear (10 800 s-1) induced aggregation of platelets obtained from normal donors in the presence or absence of lA was measured by a modified cone-plate viscometer and shear-induced vWF binding was measured by quantitative flowcytometry with monoclonal antibody known to bind exclusively to the C-terminal domain of vWF (LJ-C3) directly labeled with fluorescein isothiocyanate (FITC). P-selectin surface expression was also measured by a similar method with FITC conjugated anti-P-selectin monoclonal antibody (WGA1).Results Shear-induced platelet aggregation was inhibited by IA in a dose-dependent manner. The extent of aggregation decreased from (78.6±4.6)% in the absence of lA to (36.5±2.1 )% in the presence of lA (3.3 mmol/L) (P<0.0001, n=9) with a high shear rate of 10800 s-1. vWF binding and P-selectin expression were also inhibited by lA in a dose dependent manner. The number of binding FITC-LJ-C3 molecules increased after exposure of platelet-rich plasma to a high shear rate of 10 800 s-1 for 6 minutes, but this shear-induced increased binding platelet surface vWF molecules and P-selectin expression can be decreased in the presence of IA.Conclusion vWF binding and vWF mediated platelet activation, aggregation occurring under high shear rate were inhibited by IA. lA may be a unique antithrombotic drug inhibiting the vWF-GP Ib α interaction, and may thus facilitate drug design targeting arterial thrombosis.

  12. Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites

    Science.gov (United States)

    Kini, R. Manjunatha; Koh, Cho Yeow

    2016-01-01

    Snake venom metalloproteases, in addition to their contribution to the digestion of the prey, affect various physiological functions by cleaving specific proteins. They exhibit their activities through activation of zymogens of coagulation factors, and precursors of integrins or receptors. Based on their structure–function relationships and mechanism of action, we have defined classification and nomenclature of functional sites of proteases. These metalloproteases are useful as research tools and in diagnosis and treatment of various thrombotic and hemostatic conditions. They also contribute to our understanding of molecular details in the activation of specific factors involved in coagulation, platelet aggregation and matrix biology. This review provides a ready reference for metalloproteases that interfere in blood coagulation, fibrinolysis and platelet aggregation. PMID:27690102

  13. Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites

    Directory of Open Access Journals (Sweden)

    R. Manjunatha Kini

    2016-09-01

    Full Text Available Snake venom metalloproteases, in addition to their contribution to the digestion of the prey, affect various physiological functions by cleaving specific proteins. They exhibit their activities through activation of zymogens of coagulation factors, and precursors of integrins or receptors. Based on their structure–function relationships and mechanism of action, we have defined classification and nomenclature of functional sites of proteases. These metalloproteases are useful as research tools and in diagnosis and treatment of various thrombotic and hemostatic conditions. They also contribute to our understanding of molecular details in the activation of specific factors involved in coagulation, platelet aggregation and matrix biology. This review provides a ready reference for metalloproteases that interfere in blood coagulation, fibrinolysis and platelet aggregation.

  14. 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

    2017-01-01

    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.

  15. Evening primrose oil ameliorates platelet aggregation and improves cardiac recovery in myocardial-infarct hypercholesterolemic rats.

    Science.gov (United States)

    Abo-Gresha, Noha M; Abel-Aziz, Eman Z; Greish, Sahar M

    2014-01-01

    Omega-6 polyunsaturated fatty acids (n-6 PUFA) are well known for their role in cardiovascular disease (CVD). We proposed that Evening prime rose oil (EPO) can improve the outcome of a heart with myocardial infarction (MI) in the presence of diet-induced hyperaggregability. This study was designed to examine its cholesterol lowering, antithrombotic and anti-inflammatory effects. High fat diet was administered for 4 weeks then MI was induced by isoproterenol (85 mg/kg/s.c./24 h). Treatment with EPO (5 or 10 gm/kg/day) for 6 weeks improved the electrocardiographic pattern, serum lipid profile, cardiac biomarkers as well as Platelet aggregation percent. We reported decreased serum level of TNF-α, IL-6 and COX-2 with attenuation of TNF-α and TGF-β in the cardiac homogenate. Moreover, histopathology revealed marked amelioration. Finally, we provide evidence that EPO improve cardiac recovery in hypercholesterolemic myocardial infarct rats. These effects are attributed to direct hypocholesterolemic effect and indirect effect on the synthesis of eicosanoids (prostaglandins, cytokines).

  16. The value of flow cytometry in the measurement of platelet activation and aggregation in human immunodeficiency virus infection.

    Science.gov (United States)

    Nkambule, Bongani B; Davison, Glenda; Ipp, Hayley

    2015-01-01

    Human immunodeficiency deficiency virus (HIV) infection is associated with chronic inflammation and an increased risk of thrombotic events. Activated platelets (PLTs) play an important role in both thrombosis and inflammation, and HIV has been shown to induce PLT activation by both direct and indirect mechanisms. P-selectin (CD62P) is a well-described marker of PLT activation, and PLT glycoprotein (GP) IV (CD36) has been identified as a marker of PLT aggregation. Data on PLT function in the context of HIV infection remain inconclusive. Laboratory techniques, such as flow cytometry, enable the assessment of PLTs in their physiological state and environment, with minimal artifactual in vitro activation and aggregation. In this study, we describe a novel flow cytometry PLT assay, which enabled the measurement of PLT function in HIV infection. Forty-one antiretroviral-naïve HIV-positive individuals and 41 HIV-negative controls were recruited from a clinic in the Western Cape. Platelet function was evaluated by assessing the response of platelets to adenosine diphosphate (ADP) at two concentrations (0.04 mM, 0.2 mM). The percentage expression and mean fluorescence intensity (MFI) of CD62P and CD36 was used to evaluate platelet function. These were then correlated with platelet (PLT) count; CD4 count; % CD38/8; viral load and D-dimers. The % CD62P levels were higher in HIV-positive patients (HIV % CD62P 11.33[5.96-29.36] vs. control 2.48[1.56-6.04]; p infection. We were able to show that, although PLTs are significantly activated in HIV compared to uninfected controls, they retain their functional capacity.

  17. Effect of pretreatment with aspirin and ticlopidine on the change of platelet aggregability after radiofrequency catheter ablation

    Institute of Scientific and Technical Information of China (English)

    王利宏; 陈君柱; 郑良荣; 陶谦民

    2002-01-01

    Eighty-two patients with supraventricular tachycardia undergoing radiofrequency catheter ablation (RFCA) were studied to observe the inhibition effect of aspirin and ticlopidine on platelet aggregability(PAG) and thromboxane B2(TXB2) of the blood samples.Patients were divided into aspirin group A.ticlopidine group B.aspirin+ticlopidine group C and control group D.PAG and TXB2 were increased clearly after RFCA in all groups(P<0.001).Treatment with aspirin or ticlopidine before operation could reduce the patelet aggregability caused by RFCA and the joint effect of two drugs(change rate of group A:52.51±12.51%;group B:54.78±11.27%;group C:30.51±10.59%;group D:91.75±21.43%;(P<0.05)was studied .The much decreased platelet aggregability after antiplatelet therapy was evidence of the potential benefit of the treatment in preventing thromboembolism after ablation.Pretreatment with aspirin and ticlopidine together is a good way to decrease palateler aggregability after RFCA.

  18. Platelet aggregation unchanged by lipoprotein-associated phospholipase A₂ inhibition: results from an in vitro study and two randomized phase I trials.

    Directory of Open Access Journals (Sweden)

    Bonnie C Shaddinger

    Full Text Available BACKGROUND: We explored the theorized upregulation of platelet-activating factor (PAF- mediated biologic responses following lipoprotein-associated phospholipase A2 (Lp-PLA2 inhibition using human platelet aggregation studies in an in vitro experiment and in 2 clinical trials. METHODS AND RESULTS: Full platelet aggregation concentration response curves were generated in vitro to several platelet agonists in human plasma samples pretreated with rilapladib (selective Lp-PLA2 inhibitor or vehicle. This was followed by a randomized, double-blind crossover study in healthy adult men (n = 26 employing a single-agonist dose assay of platelet aggregation, after treatment of subjects with 250 mg oral rilapladib or placebo once daily for 14 days. This study was followed by a second randomized, double-blind parallel-group trial in healthy adult men (n = 58 also treated with 250 mg oral rilapladib or placebo once daily for 14 days using a full range of 10 collagen concentrations (0-10 µg/ml for characterizing EC50 values for platelet aggregation for each subject. Both clinical studies were conducted at the GlaxoSmithKline Medicines Research Unit in the Prince of Wales Hospital, Sydney, Australia. EC50 values derived from multiple agonist concentrations were compared and no pro-aggregant signals were observed during exposure to rilapladib in any of these platelet studies, despite Lp-PLA2 inhibition exceeding 90%. An increase in collagen-mediated aggregation was observed 3 weeks post drug termination in the crossover study (15.4% vs baseline; 95% confidence interval [CI], 3.9-27.0, which was not observed during the treatment phase and was not observed in the parallel-group study employing a more robust EC50 examination. CONCLUSIONS: Lp-PLA2 inhibition does not enhance platelet aggregation. TRIAL REGISTRATION: 1 Study 1: ClinicalTrials.gov NCT01745458 2 Study 2: ClinicalTrials.gov NCT00387257.

  19. Synthesis of Analogues of Gingerol and Shogaol, the Active Pungent Principles from the Rhizomes of Zingiber officinale and Evaluation of Their Anti-Platelet Aggregation Effects

    Directory of Open Access Journals (Sweden)

    Hung-Cheng Shih

    2014-03-01

    Full Text Available The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads.

  20. The effects of the decaffeination of coffee samples on platelet aggregation in hyperlipidemic rats.

    Science.gov (United States)

    Silvério, Alessandra dos Santos Danziger; Pereira, Rosemary Gualberto Fonseca Alvarenga; Lima, Adriene Ribeiro; Paula, Fernanda Borges de Araújo; Rodrigues, Maria Rita; Baldissera, Lineu; Duarte, Stella Maris da Silveira

    2013-09-01

    The effect of coffee on cardiovascular diseases is still controversial. It is known that the process of decaffeination may influence the chemical constitution and, therefore, the biological effects of coffee. This study thus evaluated the effects of decaffeination on the levels of total phenols and chlorogenic acids in Coffea arabica L. samples, as well as the effects of ingesting both integral and decaffeinated coffee on the lipid profile and hemostatic and hematological parameters in normal and hyperlipidemic rats. Samples of integral and decaffeinated lyophilized coffee (Coffea arabica L., planted in Brazil) were used for chemical analysis (total phenols, chlorogenic acid and caffeine contents). For the bioassays, coffee beverages were prepared with non-lyophilized samples (10% w/v) and were filtered and administered to animals by gavage (7.2 mL/kg/day) over 30 days. On the 31st day after beginning the treatment with coffee beverages, hyperlipidemia was induced to the animals by administering Triton WR-1339 (300 mg/kg body weight). On day 32, blood was taken to determine the lipid profile, platelet aggregation, prothrombin time, partially activated thromboplastin time and hemogram. The contents of both phenolic compounds and chlorogenic acid in the integral coffee beverage were significantly lower than those in the decaffeinated coffee beverage. The animals treated with Triton WR-1339 presented a mixed hyperlipidemia. Although the decaffeination process caused a relative increase in total phenols and chlorogenic acids, the coffee drinks were unable to change the lipid profile or the hemostatic and hematological parameters in the studied animals.

  1. Use of tailored loading-dose clopidogrel in patients undergoing selected percutaneous coronary intervention based on adenosine diphosphate-mediated platelet aggregation

    Institute of Scientific and Technical Information of China (English)

    MENG Kang; L(U) Shu-zheng; ZHU Hua-gang; CHEN Xin; GE Chang-jiang; SONG Xian-tao

    2010-01-01

    Background Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention.Methods A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n=104) served as the Talcom (Taijia)group; others (n=101) received Plavix, the Plavix group, Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months.Results Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a >50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P=0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P >0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of >50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P=5.43). No acute or subacute stent thrombosis events occurred.Conclusion An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no

  2. Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract: Ex Vivo Platelet Aggregation and Serum Levels of Arachidonic Acid Metabolites

    Science.gov (United States)

    Ismail, Maznah; Tohit, Eusni Rahayu Mohd; Abdullah, Rasedee; Zhang, Yi-Da

    2016-01-01

    Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities. Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats. Ex vivo platelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified. Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg). Results. Low dose 100 mg/kg of RBE inhibited aggregation by 42.32 ± 4.31% and this was comparable with the effect of 30 mg/kg aspirin, 43.91 ± 5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2 was attenuated while prostacyclin level increased upon RBE treatment. Conclusions. RBE reduced ex vivo ADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms. PMID:27800004

  3. SDF-1α/CXCR4 Signaling in Lipid Rafts Induces Platelet Aggregation via PI3 Kinase-Dependent Akt Phosphorylation.

    Science.gov (United States)

    Ohtsuka, Hiroko; Iguchi, Tomohiro; Hayashi, Moyuru; Kaneda, Mizuho; Iida, Kazuko; Shimonaka, Motoyuki; Hara, Takahiko; Arai, Morio; Koike, Yuichi; Yamamoto, Naomasa; Kasahara, Kohji

    2017-01-01

    Stromal cell-derived factor-1α (SDF-1α)-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and phosphatidylinositol 3 kinase (PI3K). Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in human platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α also induces the phosphorylation of PDK1 at Ser241 (an upstream activator of Akt), GSK3β at Ser9 (a downstream substrate of Akt), and myosin light chain at Ser19 (a downstream element of the Akt signaling pathway). SDF-1α-induced platelet aggregation is inhibited by pretreatment with the Akt inhibitor MK-2206 in a dose-dependent manner. Furthermore, SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the raft-disrupting agent methyl-β-cyclodextrin. Sucrose density gradient analysis shows that 35% of CXCR4, 93% of the heterotrimeric G proteins Gαi-1, 91% of Gαi-2, 50% of Gβ and 4.0% of PI3Kβ, and 4.5% of Akt2 are localized in the detergent-resistant membrane raft fraction. These findings suggest that SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3K-dependent Akt phosphorylation.

  4. SDF-1α/CXCR4 Signaling in Lipid Rafts Induces Platelet Aggregation via PI3 Kinase-Dependent Akt Phosphorylation

    Science.gov (United States)

    Hayashi, Moyuru; Kaneda, Mizuho; Iida, Kazuko; Shimonaka, Motoyuki; Hara, Takahiko; Arai, Morio; Koike, Yuichi; Yamamoto, Naomasa; Kasahara, Kohji

    2017-01-01

    Stromal cell-derived factor-1α (SDF-1α)-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and phosphatidylinositol 3 kinase (PI3K). Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in human platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α also induces the phosphorylation of PDK1 at Ser241 (an upstream activator of Akt), GSK3β at Ser9 (a downstream substrate of Akt), and myosin light chain at Ser19 (a downstream element of the Akt signaling pathway). SDF-1α-induced platelet aggregation is inhibited by pretreatment with the Akt inhibitor MK-2206 in a dose-dependent manner. Furthermore, SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the raft-disrupting agent methyl-β-cyclodextrin. Sucrose density gradient analysis shows that 35% of CXCR4, 93% of the heterotrimeric G proteins Gαi-1, 91% of Gαi-2, 50% of Gβ and 4.0% of PI3Kβ, and 4.5% of Akt2 are localized in the detergent-resistant membrane raft fraction. These findings suggest that SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3K-dependent Akt phosphorylation. PMID:28072855

  5. Isolation of bothrasperin, a disintegrin with potent platelet aggregation inhibitory activity, from the venom of the snake Bothrops asper

    Directory of Open Access Journals (Sweden)

    Adrián Pinto

    2003-03-01

    Full Text Available The venom of Bothrops asper induces severe coagulation disturbances in accidentally envenomed humans. However, only few studies have been conducted to identify components that interact with the hemostatic system in this venom. In the present work, we fractionated B. asper venom in order to investigate the possible presence of inhibitors of platelet aggregation. Using a combination of gel filtration, anion-exchange chromatography, and reverse-phase high performance liquid chromatography, we isolated an acidic protein which shows a single chain composition, with a molecular mass of ~8 kDa, estimated by SDS-polyacrylamide gel electrophoresis. Its N-terminal sequence has high similarity to disintegrins isolated from different snake venoms, which are known to bind to cellular integrins such as the GPIIb/IIIa fibrinogen receptor on platelets. The purified protein exerted potent aggregation inhibitory activity on ADP-stimulated human platelets in vitro, with an estimated IC50 of 50 nM. This biological activity, together with the biochemical characteristics observed, demonstrate that the protein isolated from B. asper venom is a disintegrin, hereby named "bothrasperin". This is the first disintegrin isolated from Central American viperid snake species.El veneno de la serpiente Bothrops asper induce graves alteraciones de la coagulación en los humanos accidentalmente envenenados. Sin embargo, se han realizado pocos estudios para identificar los componentes del veneno que interactúan con el sistema hemostático. En el presente trabajo, fraccionamos el veneno de B. asper para investigar la posible presencia de inhibidores de la agregación plaquetaria. Empleando una combinación de técnicas cromatográficas (filtración en gel, intercambio aniónico y cromatografía líquida de alto desempeño en fase reversa, aislamos una proteína acídica de cadena simple, con una masa molecular de ~8 kDa, estimada mediante electroforesis en gel de poliacrilamida con

  6. Salicylate antagonism of acetylsalicylic acid inhibition of platelet aggregation in male and female subjects: influence of citrate concentration.

    Science.gov (United States)

    Philp, R B; Paul, M L

    1986-01-01

    Platelets from volunteers were exposed for 1 min to sodium salicylate (SA) before and after the addition of acetylsalicylic acid (ASA) to produce greater than or equal to 50% inhibition of aggregation induced by arachidonic acid (AA) or collagen. SA:ASA concentrations = 20:1. SA protection against ASA inhibition was always observed even if ASA exposure time was 15 min, whereas reversal could not be demonstrated once exposure of platelets to ASA exceeded a minimum of 3-10 min with AA as the stimulus. Reversal was even less effective when collagen was the stimulus. An apparent, increased sensitivity to SA reversal of ASA inhibition in females disappeared when citrate concentration was adjusted to compensate for lower packed cell volume. The proposed male dependency for protection in ASA treatment of thromboembolic disorders cannot be explained on the basis of differences in the SA-ASA competition at platelet cyclooxygenase and, if collagen is an important in vivo stimulus of platelet interaction with damaged vessel wall, the antagonism of ASA by SA may not be important.

  7. Use of selective-serotonin reuptake inhibitors and platelet aggregation inhibitors among individuals with co-occurring atherosclerotic cardiovascular disease and depression or anxiety

    Directory of Open Access Journals (Sweden)

    J Douglas Thornton

    2016-12-01

    Full Text Available Objective: Medications commonly used to treat heart disease, anxiety, and depression can interact resulting in an increased risk of bleeding, warranting a cautious approach in medical decision making. This retrospective, descriptive study examined the prevalence and the factors associated with the use of both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor among individuals with co-occurring atherosclerotic cardiovascular disease and anxiety or depression. Methods: Respondents aged 22 years and older, alive throughout the study period, and diagnosed with co-occurring atherosclerotic cardiovascular disease and anxiety or depression (n = 1507 in years 2007 through 2013 of the Medical Expenditures Panel Survey were included. The use of treatment was grouped as follows: selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Results: Overall, 16.5% used both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, 61.2% used selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and 22.3% used neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Respondents aged over 65 years (adjusted odds ratio = 1.93 (95% confidence interval = 1.08–3.45 and having a diagnosis of diabetes (adjusted odds ratio = 1.63 (95% confidence interval = 1.15–2.31 and hypertension (adjusted odds ratio = 1.84 (95% confidence interval = 1.04–3.27 were more likely to be prescribed the combination. Conclusion: The drug interaction was prevalent in patients who are already at higher risk of health disparities and worse outcomes thus requiring vigilant evaluation.

  8. Thrombopoietin, c-Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonists-induced aggregation in platelets in vitro.

    Science.gov (United States)

    Ezumi, Y; Takayama, H; Okuma, M

    1995-10-23

    We investigated in vitro effects of recombinant human thrombopoietin (TPO), or c-Mpl ligand, on human platelets. TPO induced rapid dose-dependent tyrosine phosphorylation of several proteins. We identified Janus tyrosine kinases, Tyk2 and JAK2, and a member of STAT (signal transducers and activators of transcription) family, STAT3, as the tyrosine-phosphorylated proteins in response to TPO. TPO by itself did not cause platelet aggregation and shape change, but augmented ADP-induced aggregation in a dose-dependent manner. Acetylsalicylic acid inhibited the secondary aggregation enhanced by TPO, but not the TPO-induced potentiation of the primary aggregation. TPO modulates platelet activation possibly through protein-tyrosine phosphorylation.

  9. Effects of danshensu on platelet aggregation and thrombosis: in vivo arteriovenous shunt and venous thrombosis models in rats.

    Directory of Open Access Journals (Sweden)

    Chen Yu

    Full Text Available Danshensu, a type of dihydroxyphenyl lactic acid, is one of the most abundant active phenolic acids in the dried root of Salvia miltiorrhizae (Lamiaceae--widely used traditional Chinese medicine. The effects of danshensu on platelet aggregation and thrombus formation in rats were examined using various methods. It was found that danshensu significantly reduced thrombus weight in 2 experimental thrombosis models; dose-dependent inhibition of adenosine diphosphate (ADP and arachidonic acid (AA-induced platelet aggregation occurred in normal and blood stasis-induced rats; Danshensu also significantly mitigated blood viscosity, plasma viscosity and hematocrit levels. Moreover, danshensu significantly inhibited venous thrombosis-induced expression of cyclooxygenases-2 (COX-2 rather than cyclooxygenases-1(COX-1 in the venous walls, down regulated thromboxane B2 (TXB2 and up regulated 6-keto prostaglandin F1α (6-keto-PGF1α, normalizing the TXB2/6-keto-PGF1α ratio. In addition, danshensu did not induce gastric lesions and even had protective effects on aspirin-induced ulcer formation at doses as high as 60 mg/kg. These findings suggest that the antithrombotic and antiplatelet aggregation effects of danshensu are attributed to its highly selective inhibition of COX-2 and ability to normalize the thromboxane A2(TXA2/prostacyclin(PGI2 balance. These findings suggest that danshensu have great prospects in antithrombotic and antiplatelet therapy.

  10. Abciximab treatment in vitro after aspirin treatment in vivo has additive effects on platelet aggregation, ATP release, and P-selectin expression.

    Science.gov (United States)

    Scazziota, A; Altman, R; Rouvier, J; Gonzalez, C; Ahmed, Z; Jeske, W P; Walenga, J M; Fareed, J

    2000-12-15

    To prevent arterial thrombosis, abciximab is administered together with aspirin. However, whether or not there are benefits to combine abciximab with aspirin is not yet well defined. Healthy volunteers were studied for the effect of aspirin + abciximab using sodium arachidonate and adenosine diphosphate (ADP) alone or in combination to induce platelet activation/aggregation. Abciximab produced complete inhibition of platelet aggregation induced with ADP but only 40% inhibition of aggregation induced by 0.75-mmol/l sodium arachidonate. Abciximab added in vitro to platelet-rich plasma (PRP) from platelets from aspirin-treated donors produced an almost complete inhibition of platelet aggregation. Aspirin, and abciximab alone, did not inhibit adenosine triphosphate (ATP) release as thoroughly as aspirin + abciximab did. Abciximab (3-5 microg/ml) produced inhibition of P-selectin expression induced with 5 (from 46.2 +/- 6.0% to 27.4 +/- 7.0%, P=0.002) and 20-micromol/l ADP (from 53.1 +/- 8.1% to 35.1 +/- 11.0%, P=0.019), but no effect was observed when 0.75-mmol/l sodium arachidonate was used (P=0.721). Aspirin diminished P-selectin expression in sodium arachidonate-stimulated platelets (from 77.7 +/- 11.8% to 40.2 +/- 3.6%, P<0.0001) in non-aspirinated and platelets from aspirin-treated donors, respectively. Abciximab (3, 4, and 5 microg/ml) added to platelets from aspirin-treated donors decreased P-selectin expression in platelets stimulated with sodium arachidonate from 40.2 +/- 8.6% to 25.6 +/- 11.5% (P=0.027), to 20.5 +/- 3.5% (P<0.0001), and to 22.5 +/- 1.8% (P<0.0001). We concluded that the antiplatelet effect of abciximab is greatly increased by aspirin.

  11. Effects of ticlopidine or ticlopidine plus aspirin on platelet aggregation and ATP release in normal volunteers: why aspirin improves ticlopidine antiplatelet activity.

    Science.gov (United States)

    Altman, R; Scazziota, A; Rouvier, J; Gonzalez, C

    1999-10-01

    Aspirin and ticlopidine are used to prevent arterial thrombosis. In some clinical settings ticlopidine is administered with aspirin for improving antithrombotic effect. We administered aspirin (100 mg/day), ticlopidine (500 mg/day), or ticlopidine and aspirin for 7 days to healthy volunteers. Platelet aggregation and ATP release induced by sodium arachidonate, ADP, or a combination of both were measured. Sodium arachidonate (0.25 mmol/L), which produces no platelet aggregation, combined with adenosine diphosphate (1 mumol/L), which produced a reversible platelet aggregation of 20% after ticlopidine, resulted in a synergistic platelet aggregation response in normal (74.6 +/- 9.2%) and in ticlopidine platelet-rich plasma (59.1% +/- 14.9%, p < 0.0001). Synergism after sodium arachidonate (0.75 mmol/L) plus adenosine diphosphate (4 mumol/L) fell from 75.8% +/- 11.0% and 59.1% +/- 15.6% after ticlopidine or aspirin, respectively, to 14.8% +/- 18.0% (p < 0.0001) after ticlopidine plus aspirin. Aspirin and ticlopidine alone did not inhibit adenosine triphosphate release as thoroughly as did aspirin plus ticlopidine. Aspirin or ticlopidine does not adequately prevent platelet activity as ticlopidine plus aspirin do. Addition of aspirin to treatment with ticlopidine improves their antiplatelet activity and better results could be obtained in arterial thrombotic prevention strategies.

  12. Identification of a tsetse fly salivary protein with dual inhibitory action on human platelet aggregation.

    Directory of Open Access Journals (Sweden)

    Guy Caljon

    Full Text Available BACKGROUND: Tsetse flies (Glossina sp., the African trypanosome vectors, rely on anti-hemostatic compounds for efficient blood feeding. Despite their medical importance, very few salivary proteins have been characterized and functionally annotated. METHODOLOGY/PRINCIPAL FINDINGS: Here we report on the functional characterisation of a 5'nucleotidase-related (5'Nuc saliva protein of the tsetse fly Glossina morsitans morsitans. This protein is encoded by a 1668 bp cDNA corresponding at the genomic level with a single-copy 4 kb gene that is exclusively transcribed in the tsetse salivary gland tissue. The encoded 5'Nuc protein is a soluble 65 kDa glycosylated compound of tsetse saliva with a dual anti-hemostatic action that relies on its combined apyrase activity and fibrinogen receptor (GPIIb/IIIa antagonistic properties. Experimental evidence is based on the biochemical and functional characterization of recombinant protein and on the successful silencing of the 5'nuc translation in the salivary gland by RNA interference (RNAi. Refolding of a 5'Nuc/SUMO-fusion protein yielded an active apyrase enzyme with K(m and V(max values of 43+/-4 microM and 684+/-49 nmol Pi/min xmg for ATPase and 49+/-11 microM and 177+/-37 nmol Pi/min xmg for the ADPase activity. In addition, recombinant 5'Nuc was found to bind to GPIIb/IIIa with an apparent K(D of 92+/-25 nM. Consistent with these features, 5'Nuc potently inhibited ADP-induced thrombocyte aggregation and even caused disaggregation of ADP-triggered human platelets. The importance of 5'Nuc for the tsetse fly hematophagy was further illustrated by specific RNAi that reduced the anti-thrombotic activities in saliva by approximately 50% resulting in a disturbed blood feeding process. CONCLUSIONS/SIGNIFICANCE: These data show that this 5'nucleotidase-related apyrase exhibits GPIIb/IIIa antagonistic properties and represents a key thromboregulatory compound of tsetse fly saliva.

  13. Increased platelet aggregation and turnover in the acute phase of ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Jensen, Kristian Løkke Funck; Dalsgaard, Jens; Grove, Erik Lerkevang

    2013-01-01

    fraction, and immature platelet count) were increased in the acute phase of STEMI compared to 3 months after PPCI (p-values STEMI despite dual antiplatelet treatment with aspirin and clopidogrel. Increased platelet......Newly produced platelets are present in the acute phase of ST-elevation myocardial infarction (STEMI). This may influence the antiplatelet effect of aspirin and clopidogrel administered prior to primary percutaneous coronary intervention (PPCI). The aims of this study were to investigate...... the antiplatelet effect of aspirin and clopidogrel and evaluate platelet turnover in the acute phase of STEMI compared to a stable phase 3 months later. In this observational follow-up study on 48 STEMI patients transferred for PPCI, loading doses of aspirin (300 mg) and clopidogrel (600 mg) were given orally...

  14. One-step apexification using platelet rich fibrin matrix and mineral trioxide aggregate apical barrier

    Directory of Open Access Journals (Sweden)

    Anisha Kumar

    2014-01-01

    In one-step apexification using MTA, the technical problem encountered is controlling the overfill or underfill of MTA. The use of a matrix material helps to overcome this shortcoming. Platelet rich fibrin (PRF is an immune platelet concentrate, which can be used as a matrix, it also promotes wound healing and repair. This case report presents a case of one step apexification using MTA as an apical barrier and autologous PRF as an internal matrix.

  15. 粉防己碱对兔血小板聚集和血小板活化因子生成的影响%Effects of tetrandrine on rabbit platelet aggregation and platelet activating factor generation

    Institute of Scientific and Technical Information of China (English)

    张敏; 张乐之; 吕金胜

    1995-01-01

    目的:探讨粉防己碱(Tet)对兔血小板聚集和PAF生成的影响.方法:卡西霉素(Cal)和PAF诱导血小板聚集的聚集率和Tet对血小板聚集的抑制率被测定;给予或未给予Tet处理之血小板用Cal刺激释放PAF的量也被测定.结果:在4-64 μmol·L-1浓度范围,Tet明显抑制Cal和PAF诱导的血小板聚集.IC50值分别为8.6μmol·L-1和14.0μmol·L-1.Tet 也浓度依赖性的抑制Cal诱导血小板释放PAF,IC50值为21.0 μmol·L-1.结论:Tet抑制血小板聚集作用与抑制内源性PAF生成有关.%AIM: To study the effects of tetrandrine (Tet) on platelet aggregation and platelet activating factor (PAF) generation in rabbit platelet-rich plasma (PRP). METHODS:The aggregation rate of platelets induced by calcimycin (Cal) and PAF and the inhibition rate of Tet on platelet aggregation were measured. The amount of PAF in PRP stimulated with Cal and treated with Tet was also meaaggregation. At the final concentrations of 4PRP aggregation by Cal, there was a marked increase in PAF content. Tet dependented the release of PAF from platelets by Cal in a concentration-dependent manner, with IC50 of 21hibition effect of Tet on platelet aggregation might be concerned with the reduction of endogenous PAF generation.

  16. Fault tolerant aggregation for power system services

    DEFF Research Database (Denmark)

    Kosek, Anna Magdalena; Gehrke, Oliver; Kullmann, Daniel

    2013-01-01

    Exploiting the flexibility in distributed energy resources (DER) is seen as an important contribution to allow high penetrations of renewable generation in electrical power systems. However, the present control infrastructure in power systems is not well suited for the integration of a very large...... number of small units. A common approach is to aggregate a portfolio of such units together and expose them to the power system as a single large virtual unit. In order to realize the vision of a Smart Grid, concepts for flexible, resilient and reliable aggregation infrastructures are required...

  17. Effects of TRA-418, a novel TP-receptor antagonist, and IP-receptor agonist, on human platelet activation and aggregation.

    Science.gov (United States)

    Miyamoto, Mitsuko; Yamada, Naohiro; Ikezawa, Shiho; Ohno, Michihiro; Otake, Atsushi; Umemura, Kazuo; Matsushita, Teruo

    2003-11-01

    [4-[2-(1,1-Diphenylethylsulfanyl)-ethyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-yloxy]-acetic acid N-Methyl-d-glucamine salt (TRA-418) has both thromboxane A2 (TP)-receptor antagonist and prostacyclin (IP)-receptor agonist properties. The present study examined the advantageous effects of TRA-418 based on the dual activities, over an agent having either activity alone and also the difference in the effects of TRA-418 and a glycoprotein alphaIIb/beta3 integrin (GPIIb/IIIa) inhibitor. TRA-418 inhibited platelet GPIIb/IIIa activation as well as P-selectin expression induced by adenosine 5'-diphosphate, thrombin receptor agonist peptide 1-6 (Ser-Phe-Leu-Leu-Arg-Asn-NH2), and U-46619 in the presence of epinephrine (U-46619+ epinephrine). TRA-418 also inhibited platelet aggregation induced by those platelet-stimulants in Ca2+ chelating anticoagulant, citrate and in nonchelating anticoagulant, d-phenylalanyl-l-prolyl-l-arginyl-chloromethyl ketone (PPACK). The TP-receptor antagonist SQ-29548 inhibited only U-46619+epinephrine-induced GPIIb/IIIa activation, P-selectin expression, and platelet aggregation. The IP-receptor agonist beraprost sodium inhibited platelet activation. Beraprost also inhibited platelet aggregation induced by platelet stimulants we tested in citrate and in PPACK. The GPIIb/IIIa inhibitor abciximab blocked GPIIb/IIIa activation and platelet aggregation. However, abciximab showed slight inhibitory effects on P-selectin expression. TRA-418 is more advantageous as an antiplatelet agent than TP-receptor antagonists or IP-receptor agonists separately used. TRA-418 showed a different inhibitory profile from abciximab in the effects on P-selectin expression.

  18. A novel pentapeptide targeting integrin β3-subunit inhibits platelet aggregation and its application in rat for thrombosis prevention

    Directory of Open Access Journals (Sweden)

    Qingrong eQu

    2016-03-01

    Full Text Available Background: Antiplatelet therapy plays a pivotal role in the prevention and treatment of thrombotic diseases. We reported the screening of P1C as a novel integrin-binding peptide from the C-terminal of connective tissue growth factor. Primary study indicated that P1C has potential against platelet aggregation. Objectives: In this study, we aimed to find the shortest active unit from the P1C fragments and explore its in vivo and in vitro activities. Methods: A series of truncated P1C fragments was prepared and screened for antiplatelet activity. The most active fragment was evaluated using coagulation assays. Flow cytometry and confocal microscopy were used to determine the interaction between the peptide and the integrin. The in vivo potential was further explored using two types of rat models. Results: From a series of truncated P1C forms, a so-called P1Cm peptide of 5-amino acids, namely, IRTPK, was screened out as the shortest active unit with superior activity. Coagulation experiments and an in vivo toxicity assay demonstrated that P1Cm is safe in vivo and inhibits ADP- and TH-induced human platelet aggregation in vitro in a concentration-dependent manner. Furthermore, it has limited effect on the coagulation parameters. Flow cytometry and confocal microscopy experiments consistently indicated that the peptide specifically binds the β3-subunit of integrin on platelets. Further experiments using rat models of artery-vein shunt and carotid arterial thrombosis illustrated that P1Cm can effectively prevent thrombosis formation. Conclusion: All the results suggested that P1Cm may be a new, promising antithrombotic alternative to currently available antiplatelet treatments.

  19. [Induction of native platelets aggregation by incubation media of the UV irradiated leukocytes: possible role of the photo-induced ADP release].

    Science.gov (United States)

    Anosov, A K; Gorbach, M M

    2014-01-01

    It is shown that during incubation after UV irradiation (22-24 hours at 7-9 degrees C) irradiated isolated rabbit leukocytes release the compound(s) which induces platelets aggregation in the native platelet rich plasma. Treatment of the incubation media of irradiated leukocytes by heat (5 minutes at 100 degrees C) does not significantly change its pro-aggregation activity. Treatment of the platelet-rich plasma by the incubation media of irradiated leukocytes without stirring induces the refractoriness of platelets to ADP. The platelets treated by ADP without stirring do not react to the incubation media of irradiated leukocytes. The absorption spectrum of the incubation media of irradiated leukocytes has the maximum at 260 nm similar to that of the absorption spectra of ADP. It is possible that UVradiation induces the ADP release from leukocytes during post-irradiation incubation. Accumulation of this substance in the incubation media may be the cause of its pro-aggregation activity for native blood platelets.

  20. Effect of nano-clay platelets on the J-aggregation of thiacyanine dye organized in Langmuir-Blodgett films: A spectroscopic investigation

    Science.gov (United States)

    Bhattacharjee, D.; Hussain, Syed Arshad; Chakraborty, S.; Schoonheydt, R. A.

    2010-09-01

    In this paper we report the effect of the incorporation of nano-dimensional clay platelets, laponite, on the J-aggregation of a thiacyanine dye N, N'-dioctadecyl thiacyanine perchlorate (NK) assembled into Langmuir-Blodgett (LB) monolayers. π- A isotherms and atomic force microscopic studies confirm the successful incorporation of clay platelets into the Langmuir monolayer of NK. J-aggregates of NK remain present in LB films lifted at lower as well as higher surface pressures in the absence of laponite clay platelets. However, with the incorporation of clay platelets, J-aggregates are formed only in LB films lifted at higher surface pressure of 30 mN/m and totally absent in the films lifted at lower surface pressures of 10 and 15 mN/m. This may be due to the formation of nano-trapping level by overlapping of clay platelets at higher surface pressure. NK molecules may get squeezed to these nano-trapping to form J-aggregates.

  1. CONSISTENT AGGREGATION IN FOOD DEMAND SYSTEMS

    OpenAIRE

    Levedahl, J. William; Reed, Albert J.; Clark, J. Stephen

    2002-01-01

    Two aggregation schemes for food demand systems are tested for consistency with the Generalized Composite Commodity Theorem (GCCT). One scheme is based on the standard CES classification of food expenditures. The second scheme is based on the Food Guide Pyramid. Evidence is found that both schemes are consistent with the GCCT.

  2. [The relationship between lipid peroxidation and platelet aggregation in atherosclerotic patients].

    Science.gov (United States)

    Gómez Calviño, C; Simón Carballo, R; Coma Alfonso, C; Sánchez de León, T; Montero Pacheco, E; Rodríguez Piloto, R

    1991-01-01

    We studied 58 patients with arterial esteno-occlusive disease, 32 diabetics and 26 nondiabetics. Some parameters of lipid metabolism and platelet function were evaluated. We show the correlations founded among these parameters and we offer a possible explanation which support this behaviour.

  3. Heparin-induced platelet aggregation (H-IPA): dose/response relationship for two low molecular weight (LMW) heparin preparations (CY 216 and CY 222)

    Energy Technology Data Exchange (ETDEWEB)

    Brace, L.D.; Fareed, J.

    1986-03-01

    The authors have previously demonstrated that heparin and a LMW heparin derivative (PK 10169) causes platelet aggregation in a dose-dependent manner that can be inhibited by antagonists of the thromboxane pathway. Using fractions of these agents separated on the basis of molecular weight (MW) by gel permeation chromatography, the authors showed that H-IPA was directly dependent upon the MW of the agents tested. In order to further examine this MW dependence, the authors tested two other LMW heparin preparations, CY 216 and CY 222 and subfractions of these agents separated on the basis of MW. Citrate anticoagulated whole blood was drawn from drug-free normal healthy donors whose platelets aggregated when heparin was added to their platelet-rich plasma (PRP). PRP was prepared, various concentrations of the agents or their subfractions were added and aggregation was monitored for 40 minutes at 37/sup 0/C. The results demonstrate that like heparin and PK 10169, CY 216 and CY 222 caused platelet aggregation in a dose and MW dependent manner. Fractions with MW less than 2500 daltons caused aggregation only at concentrations exceeding the therapeutic range of the agents. The authors conclude that the ability to cause H-IPA is an inherent property of heparin and its fractions.

  4. Triplatin, a platelet aggregation inhibitor from the salivary gland of the triatomine vector of Chagas disease, binds to TXA(2) but does not interact with glycoprotein PVI.

    Science.gov (United States)

    Ma, Dongying; Assumpção, Teresa C F; Li, Yuan; Andersen, John F; Ribeiro, José; Francischetti, Ivo M B

    2012-01-01

    Salivary glands from haematophagous animals express a notable diversity of negative modulators of platelet function. Triplatin is an inhibitor of collagen-induced platelet aggregation which has been described as an antagonist of glycoprotein VI (GPVI). Because triplatin displays sequence homology to members of the lipocalin family of proteins, we investigated whether triplatin mechanism of action could be explained by interaction with pro-haemostatic prostaglandins. Our results demonstrate that triplatin inhibits platelet aggregation induced by low doses of collagen, thromboxane A2 (TXA(2)) mimetic (U46619), and arachidonic acid (AA). On the other hand, it does not inhibit platelet aggregation by convulxin, PMA, or low-dose ADP. Isothermal titration calorimetry (ITC) revealed that triplatin binds AA, cTXA(2), TXB(2), U46619 or prostaglandin (PG)H(2) mimetic (U51605). Consistent with its ligand specificity, triplatin induces relaxation of rat aorta contracted with U46619. Triplatin also interacts with PGF(2α) and PGJ(2), but not with leukotrienes, AA or biogenic amines. Surface plasmon resonance experiments failed to demonstrate interaction of triplatin with GPVI; it also did to inhibit platelet adhesion to fibrillar or soluble collagen. Because triplatin displays sequence similarity to apolipoprotein D (ApoD) - a lipocalin associated with high-density lipoprotein, ApoD was tested as a putative TXA(2)-binding molecule. ITC failed to demonstrate binding of ApoD to all prostanoids described above, or to AA. Furthermore, ApoD was devoid of inhibitory properties towards platelets activation by AA, collagen, or U46619. In conclusion, triplatin mechanism of action has been elucidated without ambiguity as a novel TXA(2)- and PGF(2α)- binding protein. It conceivably blocks platelet aggregation and vasoconstriction, thus contributing to successful blood feeding at the vector-host interface.

  5. Surface-secreted von Willebrand factor mediates aggregation of ADP-activated platelets at moderate shear stress: facilitated by GPIb but controlled by GPIIb-IIIa.

    Science.gov (United States)

    Frojmovic, M M; Kasirer-Friede, A; Goldsmith, H L; Brown, E A

    1997-03-01

    We previously showed that ADP activation of washed human platelets in plasma-free suspensions supports aggregation at moderate shear stress (0.4-1.6 Nm-2) in Poiseuille flow. Although most activated platelets expressed maximal fibrinogen-occupied GPIIb-IIIa receptors, aggregation appeared to be independent of bound fibrinogen, but blocked by the hexapeptide GRGDSP. Here, we tested the hypothesis that von Willebrand factor (vWF) secreted and expressed on activated platelets mediates aggregation at moderate shear rates from 300 to 1000 s-1 corresponding to shear stresses from 0.3 to 1.1 Nm-2. Relatively unactivated platelets (Flow cytometric measurements with monoclonal antibody (mAb) 2.2.9 reporting on surface-bound vWF, and with mAb S12 reporting on alpha-granule secreted P-selectin, showed that 65% and 80%, respectively, of all platelets were maximally activated with respect to maximal secretion and surface expression of these proteins. "Resting" washed platelets exhibited both surface-bound vWF and significant P-selectin secretion. We showed that mAbs 6D1 and NMC4, respectively blocking the adhesive domains on the GPIb receptor recognizing vWF, and on the vWF molecule recognizing the GPIb receptor, partially inhibited ADP-induced aggregation under shear in Couette flow, the degree of inhibition increasing with increasing shear stress. In contrast, mAb 10E5, blocking the vWF binding domain on GPIIb-IIIa, essentially blocked all aggregation at the shear rates tested. We conclude that vWF, expressed on ADP-activated platelets, is at least the predominant cross-bridging molecule mediating aggregation at moderate shear stress. There is an absolute requirement for free activated GPIIb-IIIa receptors, postulated to interact with platelet-secreted, surface bound vWF. The GPIb-vWF cross-bridging reaction plays a facilitative role becoming increasingly important with increasing shear stress. Since aurin tricarboxylic acid, which blocks the GPIb binding domain on vWF, was

  6. Platelet-rich plasma: the PAW classification system.

    Science.gov (United States)

    DeLong, Jeffrey M; Russell, Ryan P; Mazzocca, Augustus D

    2012-07-01

    Platelet-rich plasma (PRP) has been the subject of hundreds of publications in recent years. Reports of its effects in tissue, both positive and negative, have generated great interest in the orthopaedic community. Protocols for PRP preparation vary widely between authors and are often not well documented in the literature, making results difficult to compare or replicate. A classification system is needed to more accurately compare protocols and results and effectively group studies together for meta-analysis. Although some classification systems have been proposed, no single system takes into account the multitude of variables that determine the efficacy of PRP. In this article we propose a simple method for organizing and comparing results in the literature. The PAW classification system is based on 3 components: (1) the absolute number of Platelets, (2) the manner in which platelet Activation occurs, and (3) the presence or absence of White cells. By analyzing these 3 variables, we are able to accurately compare publications.

  7. Piperine Inhibits the Activities of Platelet Cytosolic Phospholipase A2 and Thromboxane A2 Synthase without Affecting Cyclooxygenase-1 Activity: Different Mechanisms of Action Are Involved in the Inhibition of Platelet Aggregation and Macrophage Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Dong Ju Son

    2014-08-01

    Full Text Available PURPOSE: Piperine, a major alkaloid of black pepper (Piper nigrum and long pepper (Piper longum, was shown to have anti-inflammatory activity through the suppression of cyclooxygenase (COX-2 gene expression and enzyme activity. It is also reported to exhibit anti-platelet activity, but the mechanism underlying this action remains unknown. In this study, we investigated a putative anti-platelet aggregation mechanism involving arachidonic acid (AA metabolism and how this compares with the mechanism by which it inhibits macrophage inflammatory responses; METHODS: Rabbit platelets and murine macrophage RAW264.7 cells were treated with piperine, and the effect of piperine on the activity of AA-metabolizing enzymes, including cytosolic phospholipase A2 (cPLA2, COX-1, COX-2, and thromboxane A2 (TXA2 synthase, as well as its effect on AA liberation from the plasma membrane components, were assessed using isotopic labeling methods and enzyme immunoassay kit; RESULTS: Piperine significantly suppressed AA liberation by attenuating cPLA2 activity in collagen-stimulated platelets. It also significantly inhibited the activity of TXA2 synthase, but not of COX-1, in platelets. These results suggest that piperine inhibits platelet aggregation by attenuating cPLA2 and TXA2 synthase activities, rather than through the inhibition of COX-1 activity. On the other hand, piperine significantly inhibited lipopolysaccharide-induced generation of prostaglandin (PGE2 and PGD2 in RAW264.7 cells by suppressing the activity of COX-2, without effect on cPLA2; CONCLUSION: Our findings indicate that piperine inhibits platelet aggregation and macrophage inflammatory response by different mechanisms.

  8. Dragon's Blood extract has antithrombotic properties, affecting platelet aggregation functions and anticoagulation activities.

    Science.gov (United States)

    Xin, Nian; Li, Yu-Juan; Li, Yan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Schlappi, Michael; Deng, Yu-Lin

    2011-05-17

    Dragon's Blood from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China), as a traditional Chinese medicinal herb, was shown to have certain antithrombotic effects. A new preparation process was used to extract effective components from Dragon's Blood. A 95% ethanol extract A (EA) and a precipitate B (PB) fraction were obtained and compared. Reliability of the preparation process was validated by pharmacodynamic experiments. A rat/mouse thrombosis and blood stasis model was developed for this study, and EA and PB effects on thrombosis, platelet functions and blood coagulation activities were analyzed. It was observed that the EA fraction had significantly better inhibitory effects than the PB fraction on thrombosis (pDragon's Blood contained pharmacologically effective compounds with antithrombotic effects, partially improving platelet function and anticoagulation activity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. DBAS: A Deployable Bandwidth Aggregation System

    CERN Document Server

    Habak, Karim; Harras, Khaled A

    2012-01-01

    The explosive increase in data demand coupled with the rapid deployment of various wireless access technologies have led to the increase of number of multi-homed or multi-interface enabled devices. Fully exploiting these interfaces has motivated researchers to propose numerous solutions that aggregate their available bandwidths to increase overall throughput and satisfy the end-user's growing data demand. These solutions, however, have faced a steep deployment barrier that we attempt to overcome in this paper. We propose a Deployable Bandwidth Aggregation System (DBAS) for multi-interface enabled devices. Our system does not introduce any intermediate hardware, modify current operating systems, modify socket implementations, nor require changes to current applications or legacy servers. The DBAS architecture is designed to automatically estimate the characteristics of applications and dynamically schedule various connections or packets to different interfaces. Since our main focus is deployability, we fully i...

  10. The role of platelets in the pathogenesis of systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Giuseppe A. eRamirez

    2012-06-01

    Full Text Available Systemic sclerosis (SSc is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including systemic sclerosis. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

  11. Enhanced Shear-induced Platelet Aggregation Due to Low-temperature Storage

    Science.gov (United States)

    2013-07-01

    pathogen inactivation technologies.4,5 In principle, storage of PLTs under refrigeration (4°C), which is standard practice for red blood cells (RBCs), can...by more than 100% (i.e., twofold) compared to freshly isolated PLTs at high shear rates. Effect of cell – cell collisions and fluid shear stress on...in aggregating stored PLTs. PLT aggregation under shear is controlled by cell – cell collision frequency and the force applied to the cells .26 These

  12. Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy

    Science.gov (United States)

    Enko, Dietmar; Mangge, Harald; Münch, Andreas; Niedrist, Tobias; Mahla, Elisabeth; Metzler, Helfried; Prüller, Florian

    2017-01-01

    Introduction The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. Conclusions Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced. PMID:28392742

  13. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease.

    Science.gov (United States)

    Bordia, A; Verma, S K; Srivastava, K C

    1997-05-01

    In a placebo-controlled study the effect of ginger and fenugreek was examined on blood lipids, blood sugar, platelet aggregation, fibrinogen and fibrinolytic activity. The subjects included in this study were healthy individuals, patients with coronary artery disease (CAD), and patients with non-insulin-dependent diabetes mellitus (NIDDM) who either had CAD or were without CAD. In patients with CAD powdered ginger administered in a dose of 4 g daily for 3 months did not affect ADP- and epinephrine-induced platelet aggregation. Also, no change in the fibrinolytic activity and fibrinogen level was observed. However, a single dose of 10 g powdered ginger administered to CAD patients produced a significant reduction in platelet aggregation induced by the two agonists. Ginger did not affect the blood lipids and blood sugar. Fenugreek given in a dose of 2.5 g twice daily for 3 months to healthy individuals did not affect the blood lipids and blood sugar (fasting and post prandial). However, administered in the same daily dose for the same duration to CAD patients also with NIDDM, fenugreek decreased significantly the blood lipids (total cholesterol and triglycerides) without affecting the HDL-c. When administered in the same daily dose to NIDDM (non-CAD) patients (mild cases), fenugreek reduced significantly the blood sugar (fasting and post prandial). In severe NIDDM cases, blood sugar (both fasting and post prandial) was only slightly reduced. The changes were not significant. Fenugreek administration did not affect platelet aggregation, fibrinolytic activity and fibrinogen.

  14. [Randomised comparative study of early versus delayed surgery in hip-fracture patients on concomitant treatment with antiplatelet drugs. Determination of platelet aggregation, perioperative bleeding and a review of annual mortality].

    Science.gov (United States)

    Mas-Atance, J; Marzo-Alonso, C; Matute-Crespo, M; Trujillano-Cabello, J J; Català-Tello, N; de Miguel-Artal, M; Forcada-Calvet, P; Fernández-Martínez, J J

    2013-01-01

    A review of the perioperative management of patients with hip fractures and concomitant therapy with antiplatelet agents, and to analyse the differences in mortality and perioperative bleeding in early surgery (5 days). Platelet aggregation was measured on admission and immediately before surgery in all patients included in the study A total of 175 patients over 65 years old, with low energy hip fracture were randomised into 3 groups: Patients on antiplatelet therapy undergoing early surgery, patients on antiplatelet therapy undergoing delayed surgery, and patients not on antiplatelet therapy undergoing early surgery. The same clinical and laboratory data were collected prospectively up to 12 months for all the patients. The platelet aggregation was determined by a semi-quantitative computerised system based on impedance aggregometry in whole blood. Bleeding, transfusion requirements and analytical results showed no significant differences between groups. More than half (59.8%) of the patients not taking antiplatelet therapy had normal platelet aggregation on admission, while 13.5% of those taking antiplatelet agents did not. Multivariate analysis showed increased mortality at 12 months for the variables, low Barthel index before hip fracture (OR: 0.9-0.9) and number of transfusions (OR: 1.1-1.5). The average lenth of stay was 4.1 days greater in the delayed surgery group. Early surgery for patients receiving antiplatelet therapy has similar clinical outcomes to the delayed, but improves hospital efficiency by reducing the average length of stay. The antiplatelet drug reported by the patient showed low concordance with the determination of the platelet aggregation. Copyright © 2011 SECOT. Published by Elsevier Espana. All rights reserved.

  15. The effect of different doses and different routes of acetylsalicylic acid administration on platelet aggregation in healthy volunteers and ischemic stroke patients.

    Science.gov (United States)

    Chýlová, Miroslava; Moťovská, Zuzana; Osmančík, Pavel; Procházka, Bohumír; Kalvach, Pavel

    2015-04-01

    The purpose was to assess the effect of different doses and different routes of acetylsalicylic acid (ASA) administration on platelet aggregation and the comparison between platelet aggregation after the single and the repetitive administration of ASA in healthy individuals and in patients after ischemic stroke. The study group consists of 22 healthy individuals and 30 patients with documented ischemic stroke. Platelet aggregation was measured in healthy individuals: (a) twice before ASA and (b) 2 h after different single doses and different routes of ASA administration-(b1) 500 mg orally, (b2) 500 mg intravenously, and (b3) 100 mg orally. We measured aggregability in healthy individuals after five consecutive days of 100 mg of ASA q.d. and in patients on chronic ASA 100 mg q.d. The VerifyNow was used with results expressed in aspirin reaction units (ARU). In healthy individuals, the dose-(b1) 500 mg orally-reduced the aggregability to mean (SD) 392 (36) ARU (p administration, and the same is true for the suppression after single dose of 500 mg orally and 100 mg orally (p = 0.011). Oral dose 100 mg for 5 days in healthy individuals reduced aggregation to 405 (37) and in post-stroke patients to 433 (54). All doses of ASA, both orally and intravenously, have produced a significant reduction of platelet aggregation. Preference of the parenteral to oral application has not been established.

  16. Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, L.M.; França, C.N.; Izar, M.C.; Bianco, H.T.; Lins, L.S.; Barbosa, S.P.; Pinheiro, L.F.; Fonseca, F.A.H. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, São Paulo, SP, Brasil, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-04-15

    It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.

  17. Validation of a P2Y12-receptor specific whole blood platelet aggregation assay.

    Science.gov (United States)

    Amann, Michael; Ferenc, Miroslaw; Valina, Christian M; Bömicke, Timo; Stratz, Christian; Leggewie, Stefan; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald

    2016-11-01

    Testing of P2Y12-receptor antagonist effects can support clinical decision-making. However, most platelet function assays use only ADP as agonist which is not P2Y12-receptor specific. For this reason P2Y12-receptor specific assays have been developed by adding prostaglandin E1 (PGE1) to reduce ADP-induced platelet activation via the P2Y1-receptor. The present study sought to evaluate a P2Y12-receptor specific assay for determination of pharmacodynamic and clinical outcomes. This study enrolled 400 patients undergoing coronary stenting after loading with clopidogrel or prasugrel. ADP-induced platelet reactivity was assessed by whole blood aggregometry at multiple time points with a standard ADP assay (ADPtest) and a P2Y12-receptor specific assay (ADPtest HS, both run on Multiplate Analyzer, Roche Diagnostics). Patients were clinically followed for 1 month and all events adjudicated by an independent committee. In total, 2084 pairs of test results of ADPtest and ADPtest HS were available showing a strong correlation between results of both assays (r = 0.96, p < 0.001). These findings prevailed in multiple prespecified subgroups (e.g., age; body mass index; diabetes). Calculated cutoffs for ADPtest HS and the established cutoffs of ADPtest showed a substantial agreement for prediction of ischemic and hemorrhagic events with a Cohen's κ of 0.66 and 0.66, respectively. The P2Y12-receptor specific ADPtest HS assay appears similarly predictive for pharmacodynamic and clinical outcomes as compared to the established ADPtest assay indicating its applicability for clinical use. Further evaluation in large cohorts is needed to determine if P2Y12-receptor specific testing offers any advantage for prediction of clinical outcome.

  18. Activation of human platelets by misfolded proteins

    NARCIS (Netherlands)

    Herczenik, E.; Bouma, B.; Korporaal, J.A.; Strangi, R.; Zeng, Q.; Gros, P.; van Eck, M.; van Berkel, T.J.C.; Gebbink, M.F.B.G.; Akkerman, J.W.N.

    2007-01-01

    Objective: Protein misfolding diseases result from the deposition of insoluble protein aggregates that often contain fibrils called amyloid. Amyloids are found in Alzheimer disease, atherosclerosis, diabetes mellitus, and systemic amyloidosis,which are diseases where platelet activation might be

  19. Haemostatic role of intermediate filaments in adhered platelets: importance of the membranous system stability.

    Science.gov (United States)

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

    2013-09-01

    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.

  20. Fractal Aggregates in Tennis Ball Systems

    Science.gov (United States)

    Sabin, J.; Bandin, M.; Prieto, G.; Sarmiento, F.

    2009-01-01

    We present a new practical exercise to explain the mechanisms of aggregation of some colloids which are otherwise not easy to understand. We have used tennis balls to simulate, in a visual way, the aggregation of colloids under reaction-limited colloid aggregation (RLCA) and diffusion-limited colloid aggregation (DLCA) regimes. We have used the…

  1. Selective anti-platelet aggregation synergism between a prostacyclin-mimetic, RS93427 and the nitrodilators sodium nitroprusside and glyceryl trinitrate.

    Science.gov (United States)

    Willis, A L; Smith, D L; Loveday, M; Fulks, J; Lee, C H; Hedley, L; VanAntwerp, D

    1989-12-01

    1. Citrated platelet-rich plasma from human donors was used to examine turbidometrically the platelet aggregation response to collagen (2.5 micrograms ml-1) and ADP (1.6 microgram ml-1). 2. With collagen as an aggregating agent, the limited (35% maximal inhibition) inhibitory effects of glyceryl trinitrate (GTN, 0.78-50 micrograms ml-1) were markedly potentiated by threshold (3.3-10 ng ml-1) concentrations of RS93427, an orally active prostacyclin-mimetic. Almost complete inhibition of aggregation could then be produced. 3. A threshold concentration of RS93427 (3.3 ng ml-1) similarly potentiated the ability of sodium nitroprusside (NaNp, 0.78-10 micrograms ml-1) to inhibit collagen-induced platelet aggregation. There was an 8 fold reduction in the IC25 concentration of NaNp. 4. Threshold concentrations of the nitrodilators were also able to potentiate the anti-aggregatory effects of RS93427 (0.03-30 ng ml-1) on collagen-induced platelet aggregation. With threshold concentrations of either GTN (6.3-25 micrograms ml-1) or NaNp (0.3-1.3 microgram ml-1), the mean IC50 concentration of RS93427 was reduced 4 or 6 fold, respectively, while the IC25 concentration was reduced 6 or 10 fold, respectively. 5. No similar synergistic interactions were seen between RS93427 and the nitrodilators when ADP was used as an aggregating agent. 6. In spontaneously hypertensive rats, the dose-response for the hypotensive response to bolus doses of RS93427 was not altered by concomitant steady state infusion of a threshold dose (1 micrograms kg-1 min-1) of GTN. 7. Possible therapeutic implications of these findings are discussed.

  2. Reduced IL-35 levels are associated with increased platelet aggregation and activation in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Zhang, Xiaohui; Zhou, Yi; Xu, Lanping; Han, Wei; Chen, Huan; Chen, Yuhong; Fu, Haixia; Zhou, Shiyuan; Zhao, Jingzhong; Wang, Qianming; Feng, Feier; Zhu, Xiaolu; Liu, Kaiyan; Huang, Xiaojun

    2015-05-01

    Acute graft-versus-host disease (aGVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that suppresses the immune response. This prospective study explored IL-35 plasma levels in 65 patients after HSCT. The results revealed that the peripheral blood of patients with grades III-IV aGVHD (23.46 ng/ml) had reduced IL-35 compared to transplanted patients with grades I-II aGVHD (40.26 ng/ml, p IL-35 levels with respect to aGVHD. The patients who received lower levels of IL-35 cells in the GBM (28.0 ng/ml, p = 0.551) or lower levels of IL-35 in PBPC (53.46 ng/ml, p = 0.03) exhibited a higher incidence of aGVHD. Patients with aGVHD have increased platelet aggregation. IL-35 was added to patient blood in vitro, and platelet aggregation was inhibited by IL-35 in a dose-dependent manner. The markers of platelet activation (CD62P/PAC-1) can also be inhibited by IL-35. The results indicate that IL-35 may affect the development of aGVHD by inhibiting platelet activation and aggregation. Our data suggests that IL-35 represents a potentially effective therapeutic agent against aGVHD after allo-HSCT.

  3. Small file aggregation in a parallel computing system

    Science.gov (United States)

    Faibish, Sorin; Bent, John M.; Tzelnic, Percy; Grider, Gary; Zhang, Jingwang

    2014-09-02

    Techniques are provided for small file aggregation in a parallel computing system. An exemplary method for storing a plurality of files generated by a plurality of processes in a parallel computing system comprises aggregating the plurality of files into a single aggregated file; and generating metadata for the single aggregated file. The metadata comprises an offset and a length of each of the plurality of files in the single aggregated file. The metadata can be used to unpack one or more of the files from the single aggregated file.

  4. Maximal aggregation of polynomial dynamical systems.

    Science.gov (United States)

    Cardelli, Luca; Tribastone, Mirco; Tschaikowski, Max; Vandin, Andrea

    2017-09-19

    Ordinary differential equations (ODEs) with polynomial derivatives are a fundamental tool for understanding the dynamics of systems across many branches of science, but our ability to gain mechanistic insight and effectively conduct numerical evaluations is critically hindered when dealing with large models. Here we propose an aggregation technique that rests on two notions of equivalence relating ODE variables whenever they have the same solution (backward criterion) or if a self-consistent system can be written for describing the evolution of sums of variables in the same equivalence class (forward criterion). A key feature of our proposal is to encode a polynomial ODE system into a finitary structure akin to a formal chemical reaction network. This enables the development of a discrete algorithm to efficiently compute the largest equivalence, building on approaches rooted in computer science to minimize basic models of computation through iterative partition refinements. The physical interpretability of the aggregation is shown on polynomial ODE systems for biochemical reaction networks, gene regulatory networks, and evolutionary game theory.

  5. Modulatory effect of coffee on platelet function.

    Science.gov (United States)

    Bhaskar, Shobha; Rauf, Arun A

    2010-01-01

    Blood platelets play a major role in cardiovascular disease (CVD) and thrombosis. Conflicting information exists regarding the effect of coffee consumption on the cardiovascular system. We have investigated whether the consumption of moderate amount of coffee affect platelet functions and primary hemostasis in vivo in normal and high fat diet fed rats. Coffee fed group showed significant (P production from membrane arachidonic acid and it was decreased in coffee treated group. Platelet aggregation studies with ADP, collagen, arachidonic acid and epinephrine showed significant (P coffee fed group. Scanning electron microscopic studies revealed that platelet aggregation tendency increased in HFD group and was reduced in coffee fed group. These results indicate that coffee is active in inhibiting platelet aggregation, a critical step involved in thrombosis.

  6. Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases

    OpenAIRE

    Harifi, Ghita; SIBILIA, JEAN

    2016-01-01

    Well-recognized for their role in vascular homoeostasis, platelets may play a major role in inflammation and immunomodulation. Substantial data are emerging on the pathogenic involvement of platelets in inflammatory arthritis and autoimmune diseases, indicating the existence of crosstalk between the coagulation and inflammation system. Upon activation, platelets release pro-inflammatory platelets microparticles, which interact with leucocytes leading to joint and systemic inflammation in rheu...

  7. Recent advancements in erythrocytes, platelets, and albumin as delivery systems.

    Science.gov (United States)

    Xu, Peipei; Wang, Ruju; Wang, Xiaohui; Ouyang, Jian

    2016-01-01

    In the past few years, nanomaterial-based drug delivery systems have been applied to enhance the efficacy of therapeutics and to alleviate negative effects through the controlled delivery of targeting and releasing agents. However, few drug carriers can achieve high targeting efficacy, even when targeting modalities and surface markers are introduced. Immunological problems have also limited their wide applications. Biological drug delivery systems, such as erythrocytes, platelets, and albumin, have been extensively investigated because of their unique properties. In this review, erythrocytes, platelets, and albumin are described as efficient drug delivery systems. Their properties, applications, advantages, and limitations in disease treatment are explained. This review confirms that these systems can be used to facilitate a specific, biocompatible, and smart drug delivery.

  8. Platelet aggregation function monitored by light transmittance aggregometry and continuous platelet count%光学比浊法与连续血小板计数法监测血小板聚集功能的比较

    Institute of Scientific and Technical Information of China (English)

    关杰; 任军伟; 朱远; 傅淑宏; 白洁; 邓新立; 丛玉隆

    2013-01-01

      目的评价血小板功能检测仪PL-11应用的连续血小板计数方法(PL-11)监测血小板功能的价值。方法通过光学比浊法(light transmittance aggregometry,LTA)与PL-11连续血小板计数法检测本院2012年26例服用氯吡格雷抗凝治疗的心血管病患者和45例健康志愿者的血小板聚集功能,分析两种方法相关性及差异。结果血小板聚集诱聚剂二磷酸腺苷(adenosine diphosphate,ADP)诱导的LTA与PL-11最大血小板聚集率(maximal aggregation ratio,MAR)存在较好相关性(r=0.766,P<0.0001)。分别用LTA与PL-11检测健康志愿者组、服药患者组,最大血小板聚集率均存在统计学差异(P<0.0001)。在两组人群中,LTA测得最大血小板聚集率范围均较PL-11广。PL-11在每例标本检测过程中,各测试点提供的平均血小板体积(mean platelet volume,MPV)变化趋势与检测期间血小板聚集率变化情况一致。结论 PL-11连续血小板计数法与“金标准”的光学比浊法检测血小板聚集功能时有较好的相关性,其应用价值可供临床及实验室参考。富血小板血浆标本与全血标本可能是两种方法检测结果差异的原因。%Objective To assess the value of continuous platelet count with platelet function analyzer PL-11 in monitoring platelet function. Methods Platelet function of 26 coronary artery disease (CAD) patients admitted to our hospital in 2012 for anticoagulant therapy with clopidogrel and 45 healthy volunteers was detected by light transmittance aggregometry (LTA) and continuous platelet count with platelet function analyzer PL-11, respectively. The correlation and the different results in the two methods were analyzed. Results The adenosine diphosphate (ADP)-induced maximal aggregation ratio (MAR) detected by LTA and continuous platelet count with PL-11 was well-correlated in CAD patients and healthy volunteers (r=0.766, P<0.000 1). The MAR detected by LTA was higher

  9. A novel dynamic layer-by-layer assembled nano-scale biointerface: functionality tests with platelet adhesion and aggregate morphology influenced by adenosine diphosphate.

    Science.gov (United States)

    Watson, Melanie G; Lopez, Juan M; Paun, Mihaela; Jones, Steven A

    2013-11-01

    An improved biointerface was developed, dynamic layer-by-layer self-assembly surface (d-LbL), and utilized as a biologically-active substrate for platelet adhesion and aggregation. Possible clinical applications for this research include improved anti-coagulation surfaces. This work demonstrated the functionality of d-LbL biointerfaces in the presence of platelet-rich-plasma (PRP) with the addition of 20 μM adenosine diphosphate (ADP), a thrombus activator. The surface morphology of the experimental control, plain PRP, was compared to PRP containing additional ADP (PRP + ADP) and resulted in an expected increase of platelet adhesions along the fibrinogen d-LbL substrate. The d-LbL process was used to coat glass slides with fibrinogen, Poly (sodium 4-styrene-sulfonate), and Poly (diallydimethlyammonium chloride). Slides were exposed to PRP under flow and static conditions with and without 20 μM of ADP. Fluorescence microscopy (FM), phase contrast microscopy (PCM), atomic force microscopy (AFM), and field emission-scanning electron microscopy (FE-SEM) were used to evaluate platelet adhesions under the influence of varied shear conditions. PCM images illustrated differences between the standard LbL and d-LbL substrates. FM images provided percent surface coverage values. For high-shear conditions, percent surface coverage values increased when using ADP whereas plain PRP exposure displayed no significant increase. AFM scans also displayed higher mean peak height values and unique surface characteristics for PRP + ADP as opposed to plain PRP. FE-SEM images revealed platelet adhesions along the biointerface and unique characteristics of the d-LbL surface. In conclusion, PRP + ADP was more effective at increasing platelet aggregation, especially under high shear conditions, providing further validation of the improved biointerface.

  10. Performance of Uplink Carrier Aggregation in LTE-Advanced Systems

    DEFF Research Database (Denmark)

    Wang, Hua; Rosa, Claudio; Pedersen, Klaus

    2010-01-01

    Carrier aggregation (CA) has been proposed to aggregate two or more component carriers (CCs) to support a much wider transmission bandwidth for LTE-Advanced systems. With carrier aggregation, it is possible to schedule a user equipment (UE) on multiple component carriers simultaneously. In this p...

  11. Aggregation Pheromone System: A Real-parameter Optimization Algorithm using Aggregation Pheromones as the Base Metaphor

    Science.gov (United States)

    Tsutsui, Shigeyosi

    This paper proposes an aggregation pheromone system (APS) for solving real-parameter optimization problems using the collective behavior of individuals which communicate using aggregation pheromones. APS was tested on several test functions used in evolutionary computation. The results showed APS could solve real-parameter optimization problems fairly well. The sensitivity analysis of control parameters of APS is also studied.

  12. Platelet mimicry

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  13. Three new phenylpropanoids from the roots of Piper taiwanense and their inhibitory activities on platelet aggregation and Mycobacterium tuberculosis.

    Science.gov (United States)

    Chen, Si; Cheng, Ming-Jen; Wu, Chin-Chung; Peng, Chien-Fang; Huang, Hung-Yi; Chang, Hsun-Shuo; Wang, Chyi-Jia; Chen, Ih-Sheng

    2014-05-01

    Bioassay-guided fractionation of the active AcOEt-soluble fraction from the roots of Piper taiwanense has led to the isolation of two new phenylpropanoids, taiwanensols A and B (1 and 2, resp.), a new natural product, taiwanensol C (3), and 3-acetoxy-4-hydroxy-1-allylbenzene (4). The compounds were obtained as two isomer mixtures (1/2 and 3/4, resp.). Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds. Compounds 1-4 were evaluated for their antiplatelet and antitubercular activities. The mixtures 1/2 and 3/4 showed potent inhibitory activities against platelet aggregation induced by collagen, with IC50 values of 35.2 and 8.8 μM, respectively. In addition, 1/2 and 3/4 showed antitubercular activities against Mycobacterium tuberculosis H37Rv, with MIC values of 30.0 and 48.0 μg/ml, respectively.

  14. Clinical and radiographic comparison of platelet-rich fibrin and mineral trioxide aggregate as pulpotomy agents in primary molars

    Directory of Open Access Journals (Sweden)

    Surendra Patidar

    2017-01-01

    Full Text Available Aim: This study aimed to evaluate and compare the Platelet-rich fibrin (PRF and Mineral trioxide aggregate (MTA as a pulpotomy agent in primary molars. Material and Methods: In this study, 50 primary molars from 50 healthy children aged 5–9 years requiring pulpotomy were randomly allocated into two groups. In PRF group, after coronal pulp removal and hemostasis, remaining pulp tissue was covered with PRF preparation. In the MTA group, the pulp stumps were covered with MTA (Pro Root MTA-Root Canal Repair Material, Dentsply International Inc. paste obtained by mixing MTA powder with sterile water at a 3:1 powder to water ratio. All teeth were restored with reinforced zinc oxide eugenol base and glass – ionomer cement. Stainless steel crowns were given in both groups 24 h after treatment. Clinical evaluation was undertaken at 1, 3, and 6 months intervals whereas radiographic evaluation of the treated teeth was carried out at the interval of 6 months. Results: By the end of 6 months, the overall success rate was 90% in PRF group and 92% in MTA Group. A statistically significant difference was observed between the groups at 6 months of follow-up (P 0.05. Conclusion: Radiographic and clinical outcome in PRF group could suggest it as an acceptable alternative in pulpotomy of primary teeth. PRF holds a promising future in the area of primary tooth vital pulp therapy.

  15. Discovery and preliminary SAR of 5-arylidene-2,2-dimethyl-1,3-dioxane- 4,6-diones as platelet aggregation inhibitors.

    Science.gov (United States)

    El Maatougui, Abdelaziz; Azuaje, Jhonny; Coelho, Alberto; Cano, Ernesto; Yañez, Matilde; López, Carmen; Yaziji, Vicente; Carbajales, Carlos; Sotelo, Eddy

    2012-08-01

    We herein document the discovery of 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones as a novel family of platelet aggregation inhibitors. The preliminary optimization study enabled us to establish the most salient features of the structure-activity relationships in this series as well as to identify novel derivatives that are upto 60 times more potent than the hit structure 1 and slightly superior to the reference drug Milrinone.

  16. Functional alterations of human platelets following indium-111 labelling using different incubation media and labelling agents

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Yoshinari; Imaizumi, Masatoshi (Osaka National Hospital (Japan). Dept. of Cardiovascular Medicine and Radiological Science); Kimura, Kazufumi (Osaka Univ. (Japan). Dept. of Nuclear Medicine); Matsumoto, Masayasu; Kamada, Takenobu (Osaka Univ. (Japan). 1. Dept. of Internal Medicine)

    1991-05-01

    Human platelets were labelled in the absence of presence of plasma using {sup 111}In-labelled oxine sulphate, tropolone or 2-mercaptopyridine-N-oxide (MPO). Under in vitro and in vivo conditions, platelet functions were evaluated by measuring their aggregability, survival, recovery and early distribution. High labelling efficiency was achieved in saline labelling, whereas with plasma labelling, it was necessary to concentrate the platelet-rich plasma to 4.8x10{sup 6} platelets/{mu}l. The aggregation of platelets labelled in plasma or saline was compared with that of controls; platelets labelled in saline showed lower aggregability in 2 {mu}M ADP but not in 5 {mu}M ADP nor with collagen. No significant differences in platelet survival and recovery were noted between platelets labelled in plasma and those labelled in saline. Our results indicate that partial loss of ADP aggregability in vitro does not influence the in vivo viability of platelets labelled in saline. Scintigraphic studies showed that platelets labelled in a saline medium were temporarily sequestrated in the liver but not in the spleen or heart. Thus, platelet labelling in saline does not affect platelet function adversely, but platelets labelled in plasma are more desirable for assessing the early distribution of platelets in the reticuloendothelial system. (orig.).

  17. Tetrandrine differentially inhibits aggregation and ATP-release of rat platelets%粉防己碱特异抑制大鼠血小板聚集和ATP释放

    Institute of Scientific and Technical Information of China (English)

    陳一岳; 關超然; 許少珍

    1996-01-01

    To examine the effects of tetrandrine (Tet)on the aggregation and ATP-release of rat washed platelets induced by several platelet activators.METHODS: Gel-filtration (Sepharose 2B) was used to isolate washed platelets from adult rats and the platelet aggragation and ATP-release were measured simultaneously. RESULTS: In the presence of Ca2+ 1 mmol·L-1, Tet 300 μmol·L-1 inhibited the aggregation induced by ADP (25μmol· L- 1 ), collagen (2.5 g·L-1), and thrombin (103 unit·L-1)by 62 %, 60 %, and 34 %, respectively. It also inhibited arachidonic acid ( 1 mmol· L- 1 )-induced aggregation. Elevating intracellular Ca2+ concentration with the Ca2+ ionophore, calcimycin (30μmol· L-1), or by blocking the intracellular calcium pump with cyclopiazonic acid (5 μmol· L-1) initiated platelet aggregation, which was also inhibited by Tet. In Ca2 + -free medium, Tet still elicited an inhibitory effect on aggregation induced by ristocetin(2.5 g· L- 1). Lower concentrations of Tet (30nmol· L-1 to 3 μmol· L-1) failed to inhibit the aggregation (requiring Tet 10 - 300 μmol· L- 1 ), but strongly suppressed ATP-release induced by ADP 10μmol· L- 1, both of which were measured simultaneously in a single sample. CONCLUSION: Tet elicits a nonselective inhibitory effect on platelet aggregation not solely due to its Ca2+ antagonism and may act on a final common pathway leading to platelet aggregation. Furthermore, Tet is a much potent inhibitor of the release of ATP in platelets.

  18. Influence of Oxidative Stress on Stored Platelets

    Directory of Open Access Journals (Sweden)

    K. Manasa

    2016-01-01

    Full Text Available Platelet storage and its availability for transfusion are limited to 5-6 days. Oxidative stress (OS is one of the causes for reduced efficacy and shelf-life of platelets. The studies on platelet storage have focused on improving the storage conditions by altering platelet storage solutions, temperature, and materials. Nevertheless, the role of OS on platelet survival during storage is still unclear. Hence, this study was conducted to investigate the influence of storage on platelets. Platelets were stored for 12 days at 22°C. OS markers such as aggregation, superoxides, reactive oxygen species, glucose, pH, lipid peroxidation, protein oxidation, and antioxidant enzymes were assessed. OS increased during storage as indicated by increments in aggregation, superoxides, pH, conjugate dienes, and superoxide dismutase and decrements in glucose and catalase. Thus, platelets could endure OS till 6 days during storage, due to the antioxidant defense system. An evident increase in OS was observed from day 8 of storage, which can diminish the platelet efficacy. The present study provides an insight into the gradual changes occurring during platelet storage. This lays the foundation towards new possibilities of employing various antioxidants as additives in storage solutions.

  19. Effects of Oxidized Low Density Lipoprotein and Native LDL on Low Shear-Induced Platelet Aggregation(Special Issue in Hornor of the Retirement of Professor Makoto Iwata at the Department of Neurology, Tokyo Women's Medical University)

    OpenAIRE

    矢野, 知佐子; 山崎, 昌子; 内山, 真一郎; 岩田, 誠; YANO, Chisako; YAMAZAKI, Masako; UCHIYAMA, Shinichiro; IWATA, Makoto

    2008-01-01

    Oxidized LDL (ox-LDL) is known to be closely associated with atherosclerosis, and it is one of the sources of oxidized cellular injury. Previous studies show that ox-LDL affects platelet aggregation. We studied the effects of ox-LDL on shear-induced platelet aggregation (SIPA) and compared it with native LDL. Methods: We incubated ox-LDL with LDL and CuSO_4 for 16 hours at 37℃. We incubated platelet-rich plasma (PRP) with ox-LDL or native LDL, and measured SIP A. And we compared the effect of...

  20. Isolation, functional characterization and proteomic identification of CC2-PLA₂ from Cerastes cerastes venom: a basic platelet-aggregation-inhibiting factor.

    Science.gov (United States)

    Chérifi, Fatah; Namane, Abdelkader; Laraba-Djebari, Fatima

    2014-02-01

    Three-step chromatography and proteomic analysis have been used to purify and characterize a new basic phospholipase A₂ named CC2-PLA₂ from the venom of Cerastes cerastes. This phospholipase A₂ has been isolated to an extent of about 50-folds and its molecular weight was estimated at 13,534 Da. For CC2-PLA₂ identification and LC-MALDI-MS/MS analysis, the protein was reduced, alkylated and double hydrolyzed by lysine-C endopeptidase and trypsin. Tryptic fragments of LC-MS/MS analyzed CC2-PLA₂ showed sequence similarities with other snake venom PLA₂. This presents only 51 % (61/120 amino acid residues) sequence homology with the first PLA₂ (gi |129506|) previously purified from the same venom. The isolated CC2-PLA₂ displayed anti-aggregative effect on platelets and induced an inflammatory response characterized by leukocytosis in the peripheral blood. This inflammatory response is accompanied by a release of inflammatory mediators such as IL-6, eosinophil peroxidase and complement system. Obtained results indicate that CC2-PLA₂ induced a release of high level of pro-inflammatory (IL-6) cytokine and no effect on the level of anti-inflammatory cytokine (IL-10) in blood sera. Furthermore, eosinophil peroxidase activity and hemolytic complement effect increased in peripheral blood. Mononuclear and neutrophil cells were found predominant in the induced leucocytosis following CC2-PLA₂ administration into animals.

  1. Platelet aggregation inhibitors in primary and secondary prevention of ischemic stroke

    Science.gov (United States)

    Gorenoi, Vitali; Kulp, Werner; Greiner, Wolfgang; von der Schulenburg, Johann-Matthias

    2006-01-01

    Background The ischaemic stroke (IS) is one of the most frequent cause of death in Germany. Besides of non-drug many drug-based interventions are used in primary or secondary prevention of IS, among them the thrombocyte aggregation inhibitors (TAI). Objectives The evaluation addresses the questions on medical efficacy and cost-effectiveness of the TAI administration in the prevention of IS as compared to the management of risk factors alone as well as to the use of anticoagulant drugs. Methods The literature search for articles published after 1997 was conducted in December 2003 in the most important medical and economic databases. The medical analysis was performed on the basis of the most up-to date meta-analyses of randomised controlled trials (RCT) as well as of new published RCT. The data from the studies for stroke, bleeding complications as well as for the combined endpoint "severe vascular events" (SVE: death or stroke or myocardial infarction) were summarised in meta-analyses. In order to include grey literature contact has been taken up with the pharmaceutical manufacturers of TAI. Results are presented in a descriptive way. Results The medical analysis included data from 184 RCT (vs. placebo) and from 22 RCT (vs. anticoagulant drugs). The absolute reduction of IS (4.8% vs. 6.6%; p<0,00001) and SVE (10.0% vs. 12.4%; p<0,00001) were definitely higher than the absolute increase of bleeding complications (1.6% vs. 0.9%; p<0,00001), but relatively similar to this absolute increase in a subpopulation with a low risk for SVE. With regard to the stroke prevention, evidence of efficacy could be yielded for acetylsalicil acid (ASA), dipyridamole, cilostazol, ridogrel and the combination ASA with dipyridamole. ASA is less effective than anticoagulants in the prevention of ischaemic stroke in atrial fibrillation, however, it causes fewer bleeding complications. Low dosed ASA can be considered cost-effective in secondary prevention of ischemic stroke, which is not

  2. Platelet function tests: a comparative review

    Directory of Open Access Journals (Sweden)

    Paniccia R

    2015-02-01

    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

  3. Effect of Mirasol pathogen reduction technology system on in vitro quality of MCS+ apheresis platelets.

    Science.gov (United States)

    Mastroianni, Maria Adele; Llohn, Abid Hussain; Akkök, Çiğdem Akalın; Skogheim, Ruby; Ødegaard, Elna Rathe; Nybruket, Monica Jenssen; Flesland, Annika; Mousavi, Seyed Ali

    2013-10-01

    Reducing the risk of pathogen transmission to transfusion recipients is one of the great concerns in transfusion medicine. Important among the measures suggested to minimise pathogen transmission is pathogen reduction technology (PRT) systems. The present study examined the effects of Mirasol PRT system on MCS+ apheresis platelets in vitro quality measures during a seven-day storage period at 22°C. Statistical analysis indicated no significant difference in platelet concentrations between the control and treated platelet concentrates (PCs) during the storage period. Glucose and lactate levels were measured to determine metabolic activities of control and treated platelets. In both control and treated platelets, the amount of glucose consumed and lactate produced increased significantly with storage time, but glucose consumption and lactate production rates were significantly higher in treated platelets compared with control platelets. The mean pH of treated PCs was decreased at all time points relative to control PCs but remained within acceptable limits. The expression of P-selectin was also higher in Mirasol PRT treated platelets throughout the storage period, but differences were not statistically significant on Days 1 and 4. Finally, visual inspection of swirling indicated that Mirasol PRT treatment of platelets is associated with platelet shape change. Overall, our results show that MCS+ apheresis platelets treated with Mirasol PRT can preserve adequate in vitro properties for at least 5 days of storage.

  4. Comparison of the chemical profiles and anti-platelet aggregation effects of two "Dragon's Blood" drugs used in traditional Chinese medicine.

    Science.gov (United States)

    Yi, Tao; Chen, Hu-Biao; Zhao, Zhong-Zhen; Yu, Zhi-Ling; Jiang, Zhi-Hong

    2011-01-27

    "Dragon's Blood" has been used as a medicine since ancient times by many cultures. In traditional Chinese medicine, the resin obtained from Daemonorops draco (RDD) and the resin from Dracaena cochinchinensis (RDC) are equally prescribed as "Dragon's Blood" for facilitating blood circulation. To verify the traditional efficacy and elucidate the mechanism, the present study compared the chemical profiles and the pharmacological effects of two species of "Dragon's Blood" mainly used in China. A UPLC-MS fingerprinting method was developed to compare the chemical profiles of the two medicines. The anti-platelet aggregation effects of the two medicines induced by arachidonic acid (AA) were investigated. The chemical profiles of these two species of "Dragon's Blood" were significantly different. The characteristic constituents were found to be: flavanes in RDD and stilbenes in RDC. In the in vivo platelet inhibition test, performed with the dose of 200 mg/kg on rats, the peak inhibitory effects of RDD and RDC were 35.8% and 27.6%, respectively, compared with the control group. With the in vitro concentrations of 0.2, 0.4 and 0.8 mg/ml, RDD exerted significant inhibition of aggregation by 18.7%, 20.0%, and 61.6%, respectively, and RDC exerted significant inhibition of aggregation by 13.3%, 20.2%, and 31.6%, respectively. The fingerprinting method used here is suitable for distinguishing them. All pharmacological tests indicated that RDD was more potent than RDC against platelet aggregation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Antithrombotic effects of losartan in patients with hypertension complicated by atrial fibrillation: 4A (Angiotensin II Antagonist of platelet Aggregation in patients with Atrial fibrillation), a pilot study.

    Science.gov (United States)

    Sakamoto, Tomohiro; Kudoh, Takashi; Sakamoto, Kenji; Matsui, Kunihiko; Ogawa, Hisao

    2014-06-01

    Angiotensin receptor blockers (ARBs) are widely used for the treatment of hypertension. It has been reported that the ARB losartan has antiplatelet, anticoagulant and profibrinolytic effects experimentally. These properties could be desirable to treat hypertensive patients with high atherothrombotic and/or thromboembolic risk. To examine the antithrombotic effects of losartan in hypertension, 20 consecutive patients with hypertension complicated by atrial fibrillation (AF) were enrolled in this study. The patients were treated with losartan 50 mg for 8 weeks followed by 100 mg for 4 weeks. Blood samples were obtained from each patient at 0 (pretreatment), 8 and 12 weeks after initiating treatment. Platelet aggregability, plasma levels of tissue factor (TF) and type 1 plasminogen activator inhibitor (PAI-1) activity levels were measured. The area under the curve for small platelet aggregability decreased from 100 to 42.8% at 12 weeks (PLosartan inhibited platelet activity and coagulation factors in a dose- and time-dependent manner in patients with hypertension complicated by AF, whereas the fibrinolytic capacity was increased. The use of losartan could be advantageous in the treatment of hypertensive patients with high atherothrombotic risk.

  6. Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

    Directory of Open Access Journals (Sweden)

    Ji Young Park

    2013-01-01

    Full Text Available A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6 to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release. Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK, and different mitogen-activated protein kinases (MAPKs including extracellular signal-regulated kinase 1/2 (ERK1/2 as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia.

  7. Pathogenic role of platelets in rheumatoid arthritis and systemic autoimmune diseases

    Science.gov (United States)

    Harifi, Ghita; Sibilia, Jean

    2016-01-01

    Well-recognized for their role in vascular homoeostasis, platelets may play a major role in inflammation and immunomodulation. Substantial data are emerging on the pathogenic involvement of platelets in inflammatory arthritis and autoimmune diseases, indicating the existence of crosstalk between the coagulation and inflammation system. Upon activation, platelets release pro-inflammatory platelets microparticles, which interact with leucocytes leading to joint and systemic inflammation in rheumatoid arthritis. Platelets activation by immune complexes activate dendritic cells promoting the secretion of interferon alpha, which has a key role in the development of systemic lupus erythematous. In this review, we discuss the current data on the role of platelets in the pathophysiology of inflammatory arthritis and various autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis. PMID:27052277

  8. [Effect of lovastatin on adhesive and aggregation function of platelets in patients with arterial hypertension and dislipidemia].

    Science.gov (United States)

    Medvedev, I N; Skoriatina, I A

    2010-01-01

    The aim of the study was to evaluate efficiency of correction of lipid profile disturbances and platelet dysfunction by lovastatin in patients with arterial hypertension and dyslipidemia. Lovastatin was given to 29 patients for 4 months. The main parameters measured included dynamics of blood lipid profile, lipid peroxidation in plasma and platelets, antioxidative protection of blood fluid and platelets, platelet activity. t-Students test was used to assess statistical significance of the results. It was shown that lovastatin has beneficial effect on dyslipoproteidemia and peroxidation syndrome. Moreover, it normalizes intraplatelet regulatory mechanisms and inhibits enhanced platelet activity. Effects of lovastatin in patients with arterial hypertension and dyslipidemia persist under conditions of long-term therapy.

  9. Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study

    NARCIS (Netherlands)

    Hubbard, G.; Wolffram, S.; Vos, de C.H.; Bovy, A.G.; Gibbins, J.; Lovegrove, J.

    2006-01-01

    Epidemiological data suggest that those who consume a diet rich in quercetin-containing foods may have a reduced risk of CVD. Furthermore, in vitro and ex vivo studies have observed the inhibition of collagen-induced platelet activation by quercetin. The aim of the present study was to investigate t

  10. Soil aggregation under different management systems

    Directory of Open Access Journals (Sweden)

    Cibele Mascioli Rebello Portella

    2012-12-01

    Full Text Available Considering that the soil aggregation reflects the interaction of chemical, physical and biological soil factors, the aim of this study was evaluate alterations in aggregation, in an Oxisol under no-tillage (NT and conventional tillage (CT, since over 20 years, using as reference a native forest soil in natural state. After analysis of the soil profile (cultural profile in areas under forest management, samples were collected from the layers 0-5, 5-10, 10-20 and 20-40 cm, with six repetitions. These samples were analyzed for the aggregate stability index (ASI, mean weighted diameter (MWD, mean geometric diameter (MGD in the classes > 8, 8-4, 4-2, 2-1, 1-0.5, 0.5-0.25, and < 0.25 mm, and for physical properties (soil texture, water dispersible clay (WDC, flocculation index (FI and bulk density (Bd and chemical properties (total organic carbon - COT, total nitrogen - N, exchangeable calcium - Ca2+, and pH. The results indicated that more intense soil preparation (M < NT < PC resulted in a decrease in soil stability, confirmed by all stability indicators analyzed: MWD, MGD, ASI, aggregate class distribution, WDC and FI, indicating the validity of these indicators in aggregation analyses of the studied soil.

  11. Management of pulpal floor perforation and grade II Furcation involvement using mineral trioxide aggregate and platelet rich fibrin: A clinical report

    Directory of Open Access Journals (Sweden)

    Rhythm Bains

    2012-01-01

    Full Text Available To report the management of an iatrogenic perforation of pulpal floor in the furcation of mandibular first molar, using Mineral Trioxide Aggregate (MTA and platelet rich fibrin (PRF. Unpredictable endodontic root/pulp chamber floor perforations resulting in unacceptable high rate of clinical failure has now been a lesser threat with the advent of new technologies and biocompatible materials that utilize the applications of basic research along with tissue engineering concept in clinical practice. Present case report illustrates the use of MTA and platelet rich fibrin (PRF for the repair of the perforation defect and regeneration of the lost periodontium in furcation area. Although, histologic events and reaction of MTA with PRF is not studied so far, however, the autologous and biocompatible nature of the components used for present treatment modalities seems to be beneficial for the long term clinical results obtained in our case.

  12. PL-11血小板分析仪检测血小板计数及聚集功能的性能评价%Performance evaluation of PL-11 platelet analyzer in the detection of platelet count and platelet aggregation

    Institute of Scientific and Technical Information of China (English)

    蔡玉婵; 赵旭鸿; 韩平; 陈昌明; 李智

    2015-01-01

    目的:探讨PL-11血小板分析仪在检测血小板数量及聚集功能方面的性能。方法按照美国临床实验室标准化协会( CLSI)制定的仪器性能验证标准及我国卫生行业标准 WS/T 406-2012《临床血液学检验常规项目分析质量要求》对PL-11血小板分析仪进行血小板计数及聚集功能的性能评价。采用PL-11血小板分析仪、LBY-NJ4血小板聚集仪及TEG-5000血栓弹力图仪检测健康人群血小板聚集率,分析各仪器检测结果间的相关性。结果 PL-11血小板分析仪的批内及日间精密度均<1/3总误差(7%);携带污染率为0.32%;在(4.12~1380.4)×109/L线性范围内回归方程斜率为1.03,R2=0.993;血小板计数结果与血小板参考方法的结果符合率为84%,均符合行业标准要求。分别采用PL-11血小板分析仪、LBY-NJ4血小板聚集仪及TEG-5000血栓弹力图仪检测79例2型糖尿病患者单服用氯匹格雷前、后血小板聚集率,3种仪器之间差异均无统计学意义( P>0.05),患者服药前、后血小板聚集率差异有统计学意义(P<0.01)。结论 PL-11血小板分析仪可为临床提供准确、可靠的血小板计数及聚集功能的检测结果。%Objective To investigate the performance of PL-11 platelet analyzer in the detection of platelet count and platelet aggregation.Methods According to the instrument performance verification standards in the Clinical and Laboratory Standards Institute ( CLSI) and the Health Industry Standard of the People′s Republic of China, WS/T 406-2012:the Quality Standard of Routine Tests in Clinical Hematology, the performance of PL-11 platelet analyzer in the detection of platelet count and platelet aggregation were evaluated.Platelet aggregation rate in healthy subjects was compared for correlation, which was detected by PL-11 platelet analyzer, LBY-NJ4 platelet tester and TEG-5000 thromboelastogram

  13. Formyl-Peptide Receptor 2/3/Lipoxin A4 Receptor Regulates Neutrophil-Platelet Aggregation and Attenuates Cerebral Inflammation: Impact for Therapy in Cardiovascular Disease.

    Science.gov (United States)

    Vital, Shantel A; Becker, Felix; Holloway, Paul M; Russell, Janice; Perretti, Mauro; Granger, D Neil; Gavins, Felicity N E

    2016-05-31

    Platelet activation at sites of vascular injury is essential for hemostasis, but it is also a major pathomechanism underlying ischemic injury. Because anti-inflammatory therapies limit thrombosis and antithrombotic therapies reduce vascular inflammation, we tested the therapeutic potential of 2 proresolving endogenous mediators, annexin A1 N-terminal derived peptide (AnxA1Ac2-26) and aspirin-triggered lipoxin A4 (15-epi-lipoxin A4), on the cerebral microcirculation after ischemia/reperfusion injury. Furthermore, we tested whether the lipoxin A4 receptor formyl-peptide receptor 2/3 (Fpr2/3; ortholog to human FPR2/lipoxin A4 receptor) evoked neuroprotective functions after cerebral ischemia/reperfusion injury. Using intravital microscopy, we found that cerebral ischemia/reperfusion injury was accompanied by neutrophil and platelet activation and neutrophil-platelet aggregate formation within cerebral microvessels. Moreover, aspirin-triggered lipoxin A4 activation of neutrophil Fpr2/3 regulated neutrophil-platelet aggregate formation in the brain and inhibited the reactivity of the cerebral microvasculature. The same results were obtained with AnxA1Ac2-26 administration. Blocking Fpr2/lipoxin A4 receptor with the antagonist Boc2 reversed this effect, and treatments were ineffective in Fpr2/3 knockout mice, which displayed an exacerbated disease severity, evidenced by increased infarct area, blood-brain barrier dysfunction, increased neurological score, and elevated levels of cytokines. Furthermore, aspirin treatment significantly reduced cerebral leukocyte recruitment and increased endogenous levels of aspirin-triggered lipoxin A4, effects again mediated by Fpr2/3. Fpr2/lipoxin A4 receptor is a therapeutic target for initiating endogenous proresolving, anti-inflammatory pathways after cerebral ischemia/reperfusion injury. © 2016 American Heart Association, Inc.

  14. Surface modification of CoCr alloy using varying concentrations of phosphoric and phosphonoacetic acids: albumin and fibrinogen adsorption, platelet adhesion, activation, and aggregation studies.

    Science.gov (United States)

    Thiruppathi, Eagappanath; Larson, Mark K; Mani, Gopinath

    2015-01-01

    CoCr alloy is commonly used in various cardiovascular medical devices for its excellent physical and mechanical properties. However, the formation of blood clots on the alloy surfaces is a serious concern. This research is focused on the surface modification of CoCr alloy using varying concentrations (1, 25, 50, 75, and 100 mM) of phosphoric acid (PA) and phosphonoacetic acid (PAA) to generate various surfaces with different wettability, chemistry, and roughness. Then, the adsorption of blood plasma proteins such as albumin and fibrinogen and the adhesion, activation, and aggregation of platelets with the various surfaces generated were investigated. Contact angle analysis showed PA and PAA coatings on CoCr provided a gradient of hydrophilic surfaces. FTIR showed PA and PAA were covalently bound to CoCr surface and formed different bonding configurations depending on the concentrations of coating solutions used. AFM showed the formation of homogeneous PA and PAA coatings on CoCr. The single and dual protein adsorption studies showed that the amount of albumin and fibrinogen adsorbed on the alloy surfaces strongly depend on the type of PA and PAA coatings prepared by different concentrations of coating solutions. All PA coated CoCr showed reduced platelet adhesion and activation when compared to control CoCr. Also, 75 and 100 mM PA-CoCr showed reduced platelet aggregation. For PAA coated CoCr, no significant difference in platelet adhesion and activation was observed between PAA coated CoCr and control CoCr. Thus, this study demonstrated that CoCr can be surface modified using PA for potentially reducing the formation of blood clots and improving the blood compatibility of the alloy.

  15. Impact of Dabigatran versus Phenprocoumon on ADP Induced Platelet Aggregation in Patients with Atrial Fibrillation with or without Concomitant Clopidogrel Therapy (the Dabi-ADP-1 and Dabi-ADP-2 Trials

    Directory of Open Access Journals (Sweden)

    Amadea M. Martischnig

    2015-01-01

    Full Text Available Background. A relevant number of patients receive triple therapy with clopidogrel, aspirin, and oral anticoagulation. Clopidogrel’s efficacy on ADP induced platelet function may be influenced by concomitant antithrombotic therapies. Data regarding the effect of dabigatran on platelet function is limited to in vitro studies and healthy individuals. Methods. The “Dabi-ADP-1” and “Dabi-ADP-2” trials randomized patients with atrial fibrillation to either dabigatran or phenprocoumon for a 2-week period. In Dabi-ADP-1 (n=70 patients with clopidogrel therapy were excluded and in Dabi-ADP-2 (n=46 patients had to be treated concomitantly with clopidogrel. The primary endpoint was ADP-induced platelet aggregation between dabigatran and phenprocoumon at 14 days. Secondary endpoints were ADPtest HS-, TRAP-, and COL-induced platelet aggregation. Results. There was no significant difference regarding the primary endpoint between both groups in either trial (Dabi-ADP-1: Dabigatran: 846 [650–983] AU × min versus phenprocoumon: 839 [666–1039] AU × min, P=0.90 and Dabi-ADP-2: 326 [268–462] versus 350 [214–535], P=0.70 or regarding the secondary endpoints, ADPtest HS-, TRAP-, and COL-induced platelet aggregation. Conclusion. Dabigatran as compared to phenprocoumon has no impact on ADP-induced platelet aggregation in atrial fibrillation patients neither with nor without concomitant clopidogrel therapy.

  16. Antimicrobial, antioxidant, cytotoxicity and platelet aggregation inhibitory activity of a novel molecule isolated and characterized from mango ginger (Curcuma amada Roxb.) rhizome

    Indian Academy of Sciences (India)

    R S Policegoudra; K Rehna; L Jaganmohan Rao; S M Aradhya

    2010-06-01

    Mango ginger (Curcuma amada Roxb.) rhizome is used in the manufacture of pickles and other food preparations due to its unique raw mango flavour. The chloroform extract of mango ginger rhizome was subjected to antibacterial activity-guided purification by repeated silica gel column chromatography to obtain a pure compound. The structure of the isolated compound was deduced by analysing UV, IR, LC-MS and 2D-HMQCT NMR spectral data, and named it as amadaldehyde, a novel compound. It exhibited a wide range of antibacterial activity with potential bactericidal activity against several bacteria. The purified compound also exhibited antioxidant activity, cytotoxicity and platelet aggregation inhibitory activities.

  17. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes

    DEFF Research Database (Denmark)

    Storey, Robert F; Husted, Steen; Harrington, Robert A

    2007-01-01

    that has been studied in ACS patients in comparison with clopidogrel (DISPERSE-2 study). METHODS: Patients were randomized to receive either AZD6140 90 mg twice a day, AZD6140 180 mg twice a day, or clopidogrel 75 mg once a day for up to 12 weeks in a double-blind, double-dummy design. One......-half the patients allocated AZD6140 received a 270-mg loading dose. Patients randomized to receive clopidogrel were given a 300-mg loading dose unless they had already been treated with clopidogrel. Adenosine diphosphate-induced platelet aggregation was assessed by optical aggregometry on day 1 and at 4-week...

  18. Vascular endothelium and platelet preparations for the prediction of xenobiotic effects on the vascular system.

    Science.gov (United States)

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

    1985-01-01

    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.

  19. 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.

    Science.gov (United States)

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

    2016-04-30

    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.

  20. 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.

    Science.gov (United States)

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

    2014-10-01

    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.

  1. One-step apexification in immature tooth using grey mineral trioxide aggregate as an apical barrier and autologus platelet rich fibrin membrane as an internal matrix

    Directory of Open Access Journals (Sweden)

    Kavitarani B Rudagi

    2012-01-01

    Full Text Available Immature teeth with necrotic pulp and periapical lesion are difficult to treat via conventional endodontic therapy. Numerous procedures and materials have been utilized to induce root-end barrier formation. Traditionally, calcium hydroxide has been the material of choice for the apexification of immature permanent teeth; however, Mineral Trioxide Aggregate holds significant promise as an alternative to multiple treatments with calcium hydroxide. One of the technical problems associated with the placement of the restorative materials used as artificial barrier is to prevent overfill and underfill. Using a matrix avoids the extrusion of the material into the periodontal tissues. This case report presents the successful healing and apexification with combined use of Mineral Trioxide Aggregate as an apical barrier, and autologus platelet rich fibrin membrane as an internal matrix.

  2. Successful treatment of ibrutinib-associated central nervous system hemorrhage with platelet transfusion support

    Science.gov (United States)

    Stiefel, Michael F.; Barrientos, Jacqueline; Shaikh, Azfar; Ahmed, Nasir; Baskind, Paul; Liu, Delong

    2016-01-01

    Ibrutinib is a novel targeted therapy for B-cell malignancies. Hemorrhagic events were reported in the original trials, however the mechanism of bleeding is just being elucidated. Recent studies have demonstrated platelet dysfunction as a mechanism of bleeding. Currently we report two patients who developed life-threatening central nervous system hemorrhage while receiving ibrutinib for chronic lymphoid leukemia (CLL) and mantle cell lymphoma, respectively. Both patients improved rapidly after platelet transfusions even though their platelet counts were normal or only mildly reduced at the time of hemorrhage. We suggest that platelet transfusions can ameliorate the platelet dysfunction defect of ibrutinib and can support the patient through the critical period until new platelet production occurs. PMID:27583253

  3. VerifyNow and VASP phosphorylation assays give similar results for patients receiving clopidogrel, but they do not always correlate with platelet aggregation.

    Science.gov (United States)

    Bidet, Audrey; Jais, Catherine; Puymirat, Etienne; Coste, Pierre; Nurden, Alan; Jakubowski, Joseph; Nurden, Paquita

    2010-01-01

    Point-of-care testing permits an evaluation of the efficacy of drugs used in the treatment of acute coronary syndromes (ACS). An increased risk of thrombosis after coronary stenting for ACS patients treated with aspirin and clopidogrel has been linked to high platelet reactivity and, for certain patients, poor drug response. The objective of our study was to compare the VerifyNow-P2Y12 device with the VASP (vasodilator-stimulated phosphoprotein) phosphorylation assay and ADP-induced platelet aggregation as assessed by light transmission aggregometry in a group of 81 ACS patients (100 tests) treated in our hospital. There was a good correlation between VerifyNow-P2Y12 and VASP especially during the chronic phase of one month or more after the ischemic event, whereas discordance was sometimes seen with platelet aggregometry. The rapidity and ease of use of the VerifyNow device suggests that it has a valuable place in point-of-care testing of ACS patients.

  4. Rapid Purification and Procoagulant and Platelet Aggregating Activities of Rhombeobin: A Thrombin-Like/Gyroxin-Like Enzyme from Lachesis muta rhombeata Snake Venom

    Directory of Open Access Journals (Sweden)

    Frank Denis Torres-Huaco

    2013-01-01

    Full Text Available We report a rapid purification method using one-step chromatography of SVSP Rhombeobin (LMR-47 from Lachesis muta rhombeata venom and its procoagulant activities and effects on platelet aggregation. The venom was fractionated by a single chromatographic step in RP-HPLC on a C8 Discovery BIO Wide Pore, showing high degree of molecular homogeneity with molecular mass of 47035.49 Da. Rhombeobin showed amidolytic activity upon BAρNA, with a broad optimum pH (7–10 and was stable in solution up to 60°C. The amidolytic activity was inhibited by serine proteinase inhibitors and reducing agents, but not chelating agents. Rhombeobin showed high coagulant activity on mice plasma and bovine fibrinogen. The deduced amino acid sequence of Rhombeobin showed homology with other SVSPs, especially with LM-TL (L. m. muta and Gyroxin (C. d. terrificus. Rhombeobin acts, in vitro, as a strong procoagulant enzyme on mice citrated plasma, shortening the APTT and PT tests in adose-dependent manner. The protein showed, “ex vivo”, a strong defibrinogenating effect with 1 µg/animal. Lower doses activated the intrinsic and extrinsic coagulation pathways and impaired the platelet aggregation induced by ADP. Thus, this is the first report of a venom component that produces a venom-induced consumptive coagulopathy (VICC.

  5. Engineering new bone via a minimally invasive route using human bone marrow-derived stromal cell aggregates, microceramic particles, and human platelet-rich plasma gel.

    Science.gov (United States)

    Chatterjea, Anindita; Yuan, Huipin; Fennema, Eelco; Burer, Ruben; Chatterjea, Supriyo; Garritsen, Henk; Renard, Auke; van Blitterswijk, Clemens A; de Boer, Jan

    2013-02-01

    There is a rise in the popularity of arthroscopic procedures in orthopedics. However, the majority of cell-based bone tissue-engineered constructs (TECs) rely on solid preformed scaffolding materials, which require large incisions and extensive dissections for placement at the defect site. Thus, they are not suitable for minimally invasive techniques. The aim of this study was to develop a clinically relevant, easily moldable, bone TEC, amenable to minimally invasive techniques, using human mesenchymal stromal cells (hMSCs) and calcium phosphate microparticles in combination with an in situ forming platelet-rich plasma gel obtained from human platelets. Most conventional TECs rely on seeding and culturing single-cell suspensions of hMSCs on scaffolds. However, for generating TECs amenable to the minimally invasive approach, it was essential to aggregate the hMSCs in vitro before seeding them on the scaffolds as unaggregated MSCs did not generate any bone. Twenty four hours of in vitro aggregation was determined to be optimal for maintaining cell viability in vitro and bone formation in vivo. Moreover, no statistically significant difference was observed in the amount of bone formed when the TECs were implanted via an open approach or a minimally invasive route. TECs generated using MSCs from three different human donors generated new bone through the minimally invasive route in a reproducible manner, suggesting that these TECs could be a viable alternative to preformed scaffolds employed through an open surgery for treating bone defects.

  6. 蒺藜总黄酮对大鼠血小板黏附和聚集功能的影响%Effects of total flavonoid glycosides of Tribulus terrestris L.on platelet adherence and aggregation function in rats

    Institute of Scientific and Technical Information of China (English)

    王云; 韩继举; 赵晓民; 吴亚平; 冯蕾

    2011-01-01

    目的:探讨蒺藜总黄酮对血小板黏附和聚集功能的影响.方法:选用不同药物浓度,采用体外血液灌流的方法,在低切变率下观察血小板在胶原蛋白表面上的黏附形态,计算黏附面积;利用血小板聚集仪,以二磷酸腺苷诱导大鼠血小板聚集,测定血小板最大聚集率.结果:不同浓度的蒺藜总黄酮均能明显降低血小板在胶原蛋白表面上的黏附面积(P<0.01),对照组血小板的黏附聚集成团,实验组则疏松散在或单个黏附;血小板最大聚集率在蒺藜总黄酮高、中剂量组也显著下降(P<0.01).结论:蒺藜总黄酮具有显著抑制血小板黏附和聚集的作用.%OBJECTIVE To observe the effects of Tribulus terrestris L. On platelet adherence and aggregation function. METHODS Under different concentration of the drug, the adherence appearance of platelet on collagen protein were observed and calculated the area by hemoperfusion in vitro at low shear rate; adenosine diphosphate was used to induce platelet aggregation and the maximum ratio of platelet aggregation was detected. RESULTS Total flavonoid glycosides of Tribulus terrestris L. Reduced platelet adherence area on collagen surface significantly (P<0. 01). In control group, platelet agglutinated into pieces and single platelet was rare. In experimental group, the platelet adhered loosely and there were many single spreading triangle or polygon platelets. The maximum ratio of platelet aggregation decreased significantly at higher concentration of the drug (P<0. 01). CONCLUSION The results suggest that total flavonoid glycosides of Tribulus terrestris L. Can inhibit experimental platelet adherence and aggregation.

  7. Homers regulate calcium entry and aggregation in human platelets: a role for Homers in the association between STIM1 and Orai1.

    Science.gov (United States)

    Jardin, Isaac; Albarrán, Letizia; Bermejo, Nuria; Salido, Ginés M; Rosado, Juan A

    2012-07-01

    Homer is a family of cytoplasmic adaptor proteins that play different roles in cell function, including the regulation of G-protein-coupled receptors. These proteins contain an Ena (Enabled)/VASP (vasodilator-stimulated phosphoprotein) homology 1 domain that binds to the PPXXF sequence motif, which is present in different Ca²⁺-handling proteins such as IP3 (inositol 1,4,5-trisphosphate) receptors and TRPC (transient receptor potential canonical) channels. In the present study we show evidence for a role of Homer proteins in the STIM1 (stromal interaction molecule 1)-Orai1 association, as well as in the TRPC1-IP3RII (type II IP3 receptor) interaction, which might be of relevance in platelet function. Treatment of human platelets with thapsigargin or thrombin results in a Ca²⁺-independent association of Homer1 with TRPC1 and IP3RII. In addition, thapsigargin and thrombin enhanced the association of Homer1 with STIM1 and Orai1 in a Ca²⁺-dependent manner. Interference with Homer function by introduction of the synthetic PPKKFR peptide into cells, which emulates the proline-rich sequences of the PPXXF motif, reduced STIM1-Orai1 and TRPC1- IP3RII associations, as compared with the introduction of the inactive PPKKRR peptide. The PPKKFR peptide attenuates thrombin-evoked Ca²⁺ entry and the maintenance of thapsigargin-induced store-operated Ca²⁺ entry. Finally, the PPKKFR peptide attenuated thrombin-induced platelet aggregation. The findings of the present study support an important role for Homer proteins in thrombin-stimulated platelet function, which is likely to be mediated by the support of agonist-induced Ca²⁺ entry.

  8. Acetylsalicylic Acid Daily vs Acetylsalicylic Acid Every 3 Days in Healthy Volunteers: Effect on Platelet Aggregation, Gastric Mucosa, and Prostaglandin E2 Synthesis.

    Science.gov (United States)

    Ferreira, Plinio Minghin Freitas; Gagliano-Jucá, Thiago; Zaminelli, Tiago; Sampaio, Marinalva Ferreira; Blackler, Rory Willian; Trevisan, Miriam da Silva; Novaes Magalhães, Antônio Frederico; De Nucci, Gilberto

    2016-07-01

    Substantial platelet inhibition was observed 3 days after a single administration of acetylsalicylic acid 81 mg to healthy volunteers. Here we investigate prostaglandin E2 (PGE2 ) antrum concentrations and gastrointestinal symptoms in two treatment groups: one receiving losartan and acetylsalicylic acid every day and the other receiving losartan every day and acetylsalicylic acid every 3 days. Twenty-eight healthy volunteers from both sexes received either 50 mg losartan and acetylsalicylic acid 81 mg daily or 50 mg losartan and acetylsalicylic acid 81 every 3 days with placebo on the other days. Therapy was delivered for 30 days for both groups. Gastric endoscopy was performed before and after treatment period. Biopsies were collected for PGE2 quantification. Platelet function tests were carried out before and during treatment and TXB2 release on platelet rich plasma was measured. The every 3 day low-dose acetylsalicylic acid regimen produced complete inhibition of platelet aggregation compared to the daily treatment. Thromboxane B2 release was substantially abolished for both groups during treatment. There was no significant difference on the endoscopic score of both treatment groups after the 30-day treatment (P = .215). There was over 50% suppression of antrum PGE2 content on volunteers receiving acetylsalicylic acid daily (P = .0016), while for the every 3 day dose regimen there was no significant difference between pre and post-treatment antrum PGE2 dosages (P = .4193). Since PGE2 is involved in gastric healing, we understand that this new approach could be safer and as efficient as the standard daily therapy on a long-term basis.

  9. Evaluation of elutriated single donor platelets collected and stored in a closed system.

    Science.gov (United States)

    Elias, M K; Blom, N; Rijskamp, L; Weggemans, M; Halie, M R; Das, P C; Smit Sibinga, C T

    1992-01-01

    Single donor platelets (SDPC) were collected by the elutriation technique in a closed-system integrated with large storage containers. Seven runs of SDPC were stored in a 1.5 liter polyvinyl-chloride trimellitate (PVC-TOTM) storage container, making the ratio of platelet concentrate volume to container volume 1:4.5. An equal volume of pooled multiple donor platelet concentrates (MDPC) was stored in parallel under the same conditions. All haematological data were comparable for both products, except for the degree of leukocyte contamination (5-fold increase in the pool). Under these conditions, the functional, morphological, and metabolic characteristics of elutriated platelets throughout 7-day storage were superior to those of pooled platelets. Although the platelet count was not significantly different in both types of concentrates, the mean pH of pooled MDPC fell to 6.0 on day 5 of storage. Leukocytes were shown to contribute to this pH fall. The extent of cell damage, however, as evidenced by LDH leakage (42.7 LDH units/10(11) platelets/day by differential centrifugation, compared to 5.3 units by elutriation) could not be explained solely on the basis of the leukocyte effect. This indicated that the processing method itself influences the platelet quality. By increasing the surface/volume ratio of SDPC, the initial pH of 7.1 was well maintained throughout storage, platelet metabolic rate was slowed, and the function and ultrastructure improved significantly.

  10. Thrombopoietin induces p-selectin expression on platelets and subsequent platelet/leukocyte interactions.

    Science.gov (United States)

    Tibbles, Heather E; Navara, Christopher S; Hupke, Michael A; Vassilev, Alexei O; Uckun, Fatih M

    2002-04-12

    Ligation of thrombopoietin (TPO) to the platelet c-Mpl receptor induces numerous biochemical pathways in the absence of aggregation. Two forms of recombinant TPO are currently in clinical trials for the treatment of thrombocytopenia. This study focuses on the effects of the full-length recombinant human TPO (rhTPO) on platelets in a whole blood system. Platelet-leukocyte associations (PLAs) were visualized following rhTPO stimulation as CD42b/CD 45 double positive clusters by FACS analysis. Treatment of washed platelets with rhTPO induced granule release and expression of the leukocyte adhesion receptor P-selectin (CD 62P) in the absence of aggregation and calcium mobilization. RhTPO also induced platelet-leukocyte interactions in whole blood. Following stimulation, leukocytes were recruited by platelets through P-selectin in a calcium-dependent manner. rhTPO stimulates platelet-leukocyte associations in whole blood through expression of platelet P-selectin. To our knowledge, this is the first report that identifies TPO as a promoter of platelet-leukocyte interactions.

  11. [Glycoproteins, inherited diseases of platelets, and the role of platelets in wound healing].

    Science.gov (United States)

    Nurden, Alan T; Nurden, Paquita

    2013-02-01

    Recognition that platelets have a glycocalyx rich in membrane glycoproteins prompted the discovery in France that inherited bleeding syndromes due to defects of platelet adhesion and aggregation were caused by deficiencies in major receptors at the platelet surface. Identification of the alpha IIb beta3 integrin prompted the development of powerful anti-thrombotic drugs that have gained worldwide use. Since these discoveries, the genetic causes of many other defects of platelet function and production have been elucidated, with the identification of an ADP receptor, P2 Y12, another widespread target for anti-thrombotic drugs. Discovery of the molecular basis of a rare disease of storage of biologically active proteins in platelet alpha-granules has been accompanied by the recognition of the roles of platelets in inflammation, the innate immune system and tissue repair, opening new avenues for therapeutic advances.

  12. Coordinated aggregation in complex systems:. an interdisciplinary approach

    Science.gov (United States)

    Basios, V.; Nicolis, S. C.; Deneubourg, J. L.

    2016-09-01

    The study of the topic of guided aggregation in biology brings together decision making, collective motion and the dynamical interplay between individuals and groups. At the same time it meets statistical mechanics and the physics of complex systems in a new paradigmatic thinking. We propose a research platform for implementation and for undertaking systematic studies of coordinated aggregation, in a truly multi- and inter-disciplinary fashion.

  13. Characterization Techniques for Aggregated Nanomaterials in Biological and Environmental Systems

    Science.gov (United States)

    Jeon, Seongho

    Nanoparticles, which are defined as objects with characteristic lengths in the 10--9 -- 10--7 m (nanoscale) size range, are used with increasing frequency in a wide of applications, leading to increases in nanomaterial interactions with biological and environmental systems. There is therefore considerable interest in studying the influence nanomaterials can have when inside the human body or dispersed in the ambient environment. However, nanoparticles persist as homo aggregates or heterogeneous mixtures with organic matters, such as proteins, in biological and environmental systems. A large and growing body of research confirm that nanomaterial morphology as well as the degree of aggregation between nanomaterials influences nanomaterial interactions with their surroundings. Specifically, the structures/morphologies of nanoparticles determine their overall surface areas and corresponding surface reactivity (e.g. their catalytic activity). Nanoparticle transport properties (e.g. diffusion coefficient and extent of cellular uptake) are also determined by both their structures and surface properties. Unfortunately, techniques to characterize nanomaterial size and shape quantitatively, when nanomaterials have complex geometries or persist as aggregates, are lacking. Hydrodynamic sizes of nanoparticles and their aggregates can be inferred by dynamic light scattering (DLS) or nanoparticle tracking analysis (NTA). However, since these techniques are relied on the scattering light intensity properties, sizes of polydisperse sub 30 nm particles cannot be effectively measured in those techniques. For structure inference of aggregated nanomaterials, microscopy images have been used for qualitative visual analysis, but the quantitative morphology analysis technique is yet to be developed. Five studies in this dissertation are hence aimed to develop new techniques to provide improved morphology characterization of aggregated nanomaterials in various biological and environmental

  14. Platelets and hemostasis

    Directory of Open Access Journals (Sweden)

    M. A. Panteleev

    2014-09-01

    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.

  15. In-vitro model for the ultrastructural study of the formation of thrombi in human platelets.

    Science.gov (United States)

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

    2006-03-01

    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.

  16. Expression, purification, and analysis of three recombinant ECD disintegrins (r-colombistatins) from P-III class snake venom metalloproteinases affecting platelet aggregation and SK-MEL-28 cell adhesion.

    Science.gov (United States)

    Suntravat, Montamas; Helmke, Thomas J; Atphaisit, Chairat; Cuevas, Esteban; Lucena, Sara E; Uzcátegui, Nestor L; Sánchez, Elda E; Rodriguez-Acosta, Alexis

    2016-11-01

    Crotalid venoms are rich sources of components that affect the hemostatic system. Snake venom metalloproteinases are zinc-dependent enzymes responsible for hemorrhage that also interfere with hemostasis. The disintegrin domain is a part of snake venom metalloproteinases, which involves the binding of integrin receptors. Integrins play an essential role in cancer survival and invasion, and they have been major targets for drug development and design. Both native and recombinant disintegrins have been widely investigated for their anti-cancer activities in biological systems as well as in vitro and in vivo systems. Here, three new cDNAs encoding ECD disintegrin-like domains of metalloproteinase precursor sequences obtained from a Venezuelan mapanare (Bothrops colombiensis) venom gland cDNA library have been cloned. Three different N- and C-terminal truncated ECD disintegrin-like domains of metalloproteinases named colombistatins 2, 3, and 4 were amplified by PCR, cloned into a pGEX-4T-1 vector, expressed in Escherichia coli BL21, and tested for inhibition of platelet aggregation and inhibition of adhesion of human skin melanoma (SK-Mel-28) cancer cell lines on collagen I. Purified recombinant colombistatins 2, 3, and 4 were able to inhibit ristocetin- and collagen-induced platelet aggregation. r-Colombistatins 2 showed the most potent inhibiting SK-Mel-28 cancer cells adhesion to collagen. These results suggest that colombistatins may have utility in the development of therapeutic tools in the treatment of melanoma cancers and also thrombotic diseases. Copyright © 2016. Published by Elsevier Ltd.

  17. Rubia cordifolia, Fagonia cretica linn and Tinospora cordifolia exert anti-inflammatory properties by modulating platelet aggregation and VEGF, COX-2 and VCAM gene expressions in rat hippocampal slices subjected to ischemic reperfusion injury.

    Directory of Open Access Journals (Sweden)

    A K Rawal

    2009-03-01

    Full Text Available Summary: The formation of cerebral edema and central nervous system (CNS inflammation are a result of cerebral ischemia. Pharmacological strategies to reverse or minimize acute ischemic brain injury include "antiplatelet" agents, anticoagulants, and thrombolytics. However, these therapies have either exhibited undesirable side effects or are not cost-effective for the common people. We report here the neuroprotective effects of three herbs Rubia cordifolia (RC, Fagonia cretica linn (FC and Tinospora cordifolia (TC as potent anti-inflammatory agents in view of their ability to downregulate the expressions of COX2 and VCAM genes and upregulate VEGF expression and inhibit platelet aggregation induced by multiple agonists in hypoxic-ischemic hippocampal slices. All the three herbs exhibited appreciable anti-inflammatory properties. Industrial relevance: The above work will lead to development of new anti-inflammatory drugs with less toxic preparations and has the potential to generate employment among people who will go farming of such medicinal plants.

  18. Characteristics of the THERAFLEX UV-Platelets pathogen inactivation system - an update.

    Science.gov (United States)

    Seghatchian, Jerard; Tolksdorf, Frank

    2012-04-01

    Considerable progress has been made in the last decade in producing purer, safer, leucocyte and plasma reduced platelet concentrates (PC) with an extended shelf life. The development of different pathogen inactivation technologies (PIT) has made a substantial contribution to this trend. Preceding platelet PIT (INTERCEPT Blood System/Cerus Corporation, Concord, CA, USA; MIRASOL/Caridian BCT, Lakewood, CO, USA) are based on adding a photosensitive compound to PC. The mixture is then activated by UV light in the UVB and/or UVA spectral regions. A novel procedure, THERAFLEX UV-Platelets (MacoPharma, Mouvaux, France), was recently developed that uses short-wave ultraviolet light (UVC), without addition of any photoactive agent. This technology has proven to be highly effective in sterilising bacteria (the major cause of morbidity/mortality after platelet transfusion) as well as inactivating other transfusion transmitted DNA/RNA containing pathogens and residual leucocytes. Any PIT reflects a balance between the efficacy of pathogen inactivation and preservation of platelet quality and function. A broad spectrum of in vitro tests have become available for the assessment of platelet storage lesion (PSL), aiming to better predict clinical outcome and untoward effects of platelet therapy. Recent paired studies on the release of platelet-derived cytokines, as new platelet performance indicators, revealed a parallel increase in both THERAFLEX UV-treated and control PC throughout storage, supporting the notion that the bioavailability of platelet function is not grossly affected by UVC treatment. This is corroborated by some newer technologies for proteomic analysis, showing that the THERAFLEX UV-Platelets system results in limited disruption of integrin-regulating extracellular disulfide bonds and minimal protein alterations when compared to UVB and gamma irradiation. Moreover, standard in vitro parameters reflecting activation, metabolic activity and function of platelets

  19. Argan oil prevents prothrombotic complications by lowering lipid levels and platelet aggregation, enhancing oxidative status in dyslipidemic patients from the area of Rabat (Morocco).

    Science.gov (United States)

    Haimeur, Adil; Messaouri, Hafida; Ulmann, Lionel; Mimouni, Virginie; Masrar, Azelarab; Chraibi, Abdelmjid; Tremblin, Gérard; Meskini, Nadia

    2013-07-20

    It is now established that patients with hyperlipidemia have a high risk of atherosclerosis and thrombotic complications, which are two important events responsible for the onset and progression of cardiovascular disease. In the context of managing dyslipidemia by means of dietary advice based on the consumption of argan oil, we wanted to investigate the effect of virgin argan oil on plasma lipids, and for the first time, on the platelet hyperactivation and oxidative status associated with dyslipidemia. This study concerns patients recruited in the area of Rabat in Morocco. 39 dyslipidemic (79% women) patients were recruited for our study in the area of Rabat in Morocco. They were randomly assigned to the two following groups: the argan group, in which the subjects consumed 25 mL/day of argan oil at breakfast for 3 weeks, and the control group in which argan oil was replaced by butter. After a 3-week consumption period, blood total cholesterol was significantly lower in the argan oil group, as was LDL cholesterol (23.8% and 25.6% lower, respectively). However, the HDL cholesterol level had increased by 26% at the end of the intervention period compared to baseline. Interestingly, in the argan oil group thrombin-induced platelet aggregation was lower, and oxidative status was enhanced as a result of lower platelet MDA and higher GPx activity, respectively. In conclusion, our results, even if it is not representative of the Moroccan population, show that argan oil can prevent the prothrombotic complications associated with dyslipidemia, which are a major risk factor for cardiovascular disease.

  20. Calcium-dependent synergistic interaction of platelet activating factor and epinephrine in human platelet aggregation%血小板活化因子和肾上腺素对人血小板凝集的钙依赖性协同作用

    Institute of Scientific and Technical Information of China (English)

    Sheikh Arshad SAEED; Huma RASHEED

    2003-01-01

    AIM: To investigate the mechanism (s) involved in the synergistic interaction of platelet activating factor (PAF) and epinephrine. METHODS: Blood was obtained from healthy human subjects reported to be free of medications for at least two weeks before sampling. Aggregation was monitored at 37 ℃ using Dual-channel Lumi-aggregometer.The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time.RESULTS: Platelet aggregation mediated by subthreshold concentrations of PAF (5-8 nmol/L) plus epinephrine (0.5-2 μmol/L) was inhibited by α2-receptor blocker, yohimbine, and PAF receptor antagonist WEB 2086. This synergism was inhibited by calcium channel blockers, verapamil and diltiazem. In addition, platelet aggregation by co-addition of PAF and epinephrine was also inhibited by very low concentrations of phospholipase C (PLC)inhibitor (U73122; IC50=0.2 μmol/L), the MAP kinase inhibitor, PD 98059 (IC50=3 μmol/L), and cyclooxygenase (COX-1) inhibitors including indomethacin (IC50=0.25 μmol/L), flurbiprofen (IC50=0.7 μmol/L), and piroxicam (IC50=7 μmol/L). However, COX-2 inhibitors, nimesulide (IC50=26 μmol/L), NS-398 (IC50=7 μmol/L), and etodolac (IC50=15 μmol/L) were also effective in inhibiting the aggregation. The inhibitors of protein kinase C (chelerythrine)and tyrosine kinase (genistien), and phosphatidylinositol 3-kinase inhibitor (wortmannin) had no significant effect on platelet aggregation induced by PAF and epinephrine. CONCLUSION: The synergistic effect of PAF and epinephrine on human platelet aggregation is receptor-mediated and involves the activation of PLC/Ca2+, COX and MAP kinase signalling pathways.

  1. Inhibition of smooth muscle contraction and platelet aggregation by peptide 204–212 of lipocortin 5: an attempt to define some structure requirements

    Directory of Open Access Journals (Sweden)

    K. G. Mugridge

    1993-01-01

    Full Text Available Peptide 204–212 of lipocortin (LC 5 inhibited porcine pancreatic phospholipase A2 (PLA2 induced rat stomach strip contractions and ADP induced rabbit platelet aggregation in a concentration dependent manner (IC30 of 10 μM and 400 μM, respectively. The first two amino acids are not necessary since the eptapeptide 206–212 was equipotent in both assays (IC30 of 12.5 μM and 420 μM. Of the two pentapeptides 204–208 and 208–212 only the latter showed inhibitory activity in both models although the potency was much reduced (IC30 of 170 μM and 630 μM compared with that of the parent nonapeptide. Comparison of peptide 204–212 effects with those of its analogues on LC1 and LC2 indicate that lysine 208 and aspartic acid 211 are essential in order to maintain a fully active nonapeptide.

  2. Adhesion, activation, and aggregation of blood platelets and biofilm formation on the surfaces of titanium alloys Ti6Al4V and Ti6Al7Nb.

    Science.gov (United States)

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

    2012-03-01

    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.

  3. LpMab-12 Established by CasMab Technology Specifically Detects Sialylated O-Glycan on Thr52 of Platelet Aggregation-Stimulating Domain of Human Podoplanin.

    Directory of Open Access Journals (Sweden)

    Yukinari Kato

    Full Text Available Podoplanin (PDPN, also known as Aggrus, possesses three tandem repeat of platelet aggregation-stimulating (PLAG domains in its N-terminus. Among the PLAG domains, sialylated O-glycan on Thr52 of PLAG3 is essential for the binding to C-type lectin-like receptor-2 (CLEC-2 and the platelet-aggregating activity of human PDPN (hPDPN. Although various anti-hPDPN monoclonal antibodies (mAbs have been generated, no specific mAb has been reported to target the epitope containing glycosylated Thr52. We recently established CasMab technology to develop mAbs against glycosylated membrane proteins. Herein, we report the development of a novel anti-glycopeptide mAb (GpMab, LpMab-12. LpMab-12 detected endogenous hPDPN by flow cytometry. Immunohistochemical analyses also showed that hPDPN-expressing lymphatic endothelial and cancer cells were clearly labeled by LpMab-12. The minimal epitope of LpMab-12 was identified as Asp49-Pro53 of hPDPN. Furthermore, LpMab-12 reacted with the synthetic glycopeptide of hPDPN, corresponding to 38-54 amino acids (hpp3854: 38-EGGVAMPGAEDDVVTPG-54, which carries α2-6 sialylated N-acetyl-D-galactosamine (GalNAc on Thr52. LpMab-12 did not recognize non-sialylated GalNAc-attached glycopeptide, indicating that sialylated GalNAc on Thr52 is necessary for the binding of LpMab-12 to hPDPN. Thus, LpMab-12 could serve as a new diagnostic tool for determining whether hPDPN possesses the sialylation on Thr52, a site-specific post-translational modification critical for the hPDPN association with CLEC-2.

  4. Continuation of medically necessary platelet aggregation inhibitors - acetylsalicylic acid and clopidogrel - during surgery for spinal degenerative disorders: Results in 100 patients

    Directory of Open Access Journals (Sweden)

    Reza Akhavan-Sigari

    2014-01-01

    Full Text Available Background: Patients undergoing spinal surgery while under anticoagulation therapy are at risk of developing bleeding complications, even though lower incidences have been reported for joint arthroplasty surgery. There is a gap in the medical literature examining the incidence of postoperative spinal bleeding in patients who were under anticoagulation medication at the time of surgery. Methods: We prospectively followed a consecutive cohort of 100 patients (58 male, 42 female undergoing spinal surgery. The average patient age was 48.7 years and the minimum follow up time was 12 months. Diagnosis was lumbar spinal stenosis in 20, herniated lumbar discs in 63, degenerative cervical disc disease in 3, and cervical disc herniation in 14 cases. In our study, platelet aggregation inhibitors (clopidogrel and/or acetylsalicylic acid were given for the treatment of cardiovascular and cerebrovascular thrombotic events, to reduce risk of stroke in patients who have had transient ischemia of the brain or acute coronary syndrome, and as secondary prevention of atherosclerotic events (fatal or nonfatal myocardial infarction (MI. A cessation of anticoagulants (acetylsalicylic acid or clopidogrel in our patients in the peri- and postoperative period was contraindicated. Results: Sixty-three patients were on both clopidogrel and acetylsalicylic acid and 37 on acetylsalicylic acid only. None of the patients suffered any postoperative bleeding complication. Three patients suffered postoperative wound dehiscence and one patient had an infection that required reoperation. Conclusion: The question of whether preoperative platelet aggregation inhibitors must be stopped before elective spinal surgery has never been answered in the literature. In our prospective series, we have found no increase in the risk of postoperative spinal bleeding with the use of clopidogrel or acetylsalicylic acid. This finding suggests that spine surgery can be done without stopping

  5. Inhibitory effects of Tabebuia impetiginosa inner bark extract on platelet aggregation and vascular smooth muscle cell proliferation through suppressions of arachidonic acid liberation and ERK1/2 MAPK activation.

    Science.gov (United States)

    Son, Dong-Ju; Lim, Yong; Park, Young-Hyun; Chang, Sung-Keun; Yun, Yeo-Pyo; Hong, Jin-Tae; Takeoka, Gary R; Lee, Kwang-Geun; Lee, Sung-Eun; Kim, Mi-Ran; Kim, Jeong-Han; Park, Byeoung-Soo

    2006-11-03

    The antiplatelet and antiproliferative activities of extract of Tabebuia impetiginosa inner bark (taheebo) were investigated using washed rabbit platelets and cultured rat aortic vascular smooth muscle cells (VSMCs) in vitro. n-Hexane, chloroform and ethyl acetate fractions showed marked and selective inhibition of platelet aggregation induced by collagen and arachidonic acid (AA) in a dose-dependent manner. These fractions, especially the chloroform fraction, also significantly suppressed AA liberation induced by collagen in [(3)H]AA-labeled rabbit platelets. The fractions, especially the chloroform fraction, potently inhibited cell proliferation and DNA synthesis induced by platelet derived growth factor (PDGF)-BB, and inhibited the levels of phosphorylated extracellular signal regulated kinase (ERK1/2) mitogen activated protein kinase (MAPK) stimulated by PDGF-BB, in the same concentration range that inhibits VSMC proliferation and DNA synthesis.

  6. The Use of Spinning-Disk Confocal Microscopy for the Intravital Analysis of Platelet Dynamics in Response to Systemic and Local Inflammation

    Science.gov (United States)

    Jenne, Craig N.; Wong, Connie H. Y.; Petri, Björn; Kubes, Paul

    2011-01-01

    Platelets are central players in inflammation and are an important component of the innate immune response. The ability to visualize platelets within the live host is essential to understanding their role in these processes. Past approaches have involved adoptive transfer of labelled platelets, non-specific dyes, or the use of fluorescent antibodies to tag platelets in vivo. Often, these techniques result in either the activation of the platelet, or blockade of specific platelet receptors. In this report, we describe two new methods for intravital visualization of platelet biology, intravenous administration of labelled anti-CD49b, which labels all platelets, and CD41-YFP transgenic mice, in which a percentage of platelets express YFP. Both approaches label endogenous platelets and allow for their visualization using spinning-disk confocal fluorescent microscopy. Following LPS-induced inflammation, we were able to measure a significant increase in both the number and size of platelet aggregates observed within the vasculature of a number of different tissues. Real-time observation of these platelet aggregates reveals them to be large, dynamic structures that are continually expanding and sloughing-off into circulation. Using these techniques, we describe for the first time, platelet recruitment to, and behaviour within numerous tissues of the mouse, both under control conditions and following LPS induced inflammation. PMID:21949865

  7. The use of spinning-disk confocal microscopy for the intravital analysis of platelet dynamics in response to systemic and local inflammation.

    Directory of Open Access Journals (Sweden)

    Craig N Jenne

    Full Text Available Platelets are central players in inflammation and are an important component of the innate immune response. The ability to visualize platelets within the live host is essential to understanding their role in these processes. Past approaches have involved adoptive transfer of labelled platelets, non-specific dyes, or the use of fluorescent antibodies to tag platelets in vivo. Often, these techniques result in either the activation of the platelet, or blockade of specific platelet receptors. In this report, we describe two new methods for intravital visualization of platelet biology, intravenous administration of labelled anti-CD49b, which labels all platelets, and CD41-YFP transgenic mice, in which a percentage of platelets express YFP. Both approaches label endogenous platelets and allow for their visualization using spinning-disk confocal fluorescent microscopy. Following LPS-induced inflammation, we were able to measure a significant increase in both the number and size of platelet aggregates observed within the vasculature of a number of different tissues. Real-time observation of these platelet aggregates reveals them to be large, dynamic structures that are continually expanding and sloughing-off into circulation. Using these techniques, we describe for the first time, platelet recruitment to, and behaviour within numerous tissues of the mouse, both under control conditions and following LPS induced inflammation.

  8. Reducing error in feline platelet enumeration by addition of Iloprost to blood specimens: comparison to prostaglandin E1 and EDTA.

    Science.gov (United States)

    Tvedten, Harold W; Bäcklund, Kerstin; Lilliehöök, Inger E

    2015-06-01

    Prostaglandin E1 (PGE1) and Iloprost inhibit platelet aggregation and should prevent or minimize preanalytic error with feline platelet enumeration. The objective was to compare the relative effectiveness in reducing errors in platelet enumeration by adding Iloprost to feline EDTA blood specimens in comparison to adding PGE1 or EDTA alone. In addition, a grading system for platelet aggregation in blood smears was evaluated for effectiveness in predicting prominent errors and compared to ADVIA's PLT-CLM flag. Finally, the use of plateletcrit in feline blood with platelet aggregation was evaluated. Blood specimens from 35 cats were included. Blood was collected into EDTA tubes with or without Iloprost or PGE1, and was rapidly mixed. Platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet flags were determined with an ADVIA 2120. Manual PLT was performed with a Leucoplate stain. PLT was determined by an IDEXX VetAutoread hematology analyzer (QBC). Neither addition of Iloprost nor PGE1 to EDTA blood specimens completely prevented platelet aggregation. Iloprost-treated specimens had the least severe aggregation. PGE1 was better than EDTA alone. Significant errors in PLT results were consistently identified by the grading system. ADVIA's PLT-CL flag usually predicted significant errors in PLT. QBC PLT results showed high imprecision. Manual PLT error was smaller than ADVIA PLT in EDTA specimens with aggregation. Adding Iloprost to feline blood specimens improved platelet enumeration accuracy. A grading system for severity of platelet aggregation and usually the ADVIA's PLT-CL alarm predicted specimens with significant errors in platelet enumeration. © 2015 American Society for Veterinary Clinical Pathology.

  9. Multiple peak aggregations for the Keller-Segel system

    CERN Document Server

    Seki, Yukihiro; Velázquez, Juan J L

    2012-01-01

    In this paper we derive matched asymptotic expansions for a solution of the Keller-Segel system in two space dimensions for which the amount of mass aggregation is $8\\pi N$, where $N=1,2,3,...$ Previously available asymptotics had been computed only for the case in which N=1.

  10. A Method of Data Aggregation for Wearable Sensor Systems.

    Science.gov (United States)

    Shen, Bo; Fu, Jun-Song

    2016-06-23

    Data aggregation has been considered as an effective way to decrease the data to be transferred in sensor networks. Particularly for wearable sensor systems, smaller battery has less energy, which makes energy conservation in data transmission more important. Nevertheless, wearable sensor systems usually have features like frequently dynamic changes of topologies and data over a large range, of which current aggregating methods can't adapt to the demand. In this paper, we study the system composed of many wearable devices with sensors, such as the network of a tactical unit, and introduce an energy consumption-balanced method of data aggregation, named LDA-RT. In the proposed method, we develop a query algorithm based on the idea of 'happened-before' to construct a dynamic and energy-balancing routing tree. We also present a distributed data aggregating and sorting algorithm to execute top-k query and decrease the data that must be transferred among wearable devices. Combining these algorithms, LDA-RT tries to balance the energy consumptions for prolonging the lifetime of wearable sensor systems. Results of evaluation indicate that LDA-RT performs well in constructing routing trees and energy balances. It also outperforms the filter-based top-k monitoring approach in energy consumption, load balance, and the network's lifetime, especially for highly dynamic data sources.

  11. A Method of Data Aggregation for Wearable Sensor Systems

    Directory of Open Access Journals (Sweden)

    Bo Shen

    2016-06-01

    Full Text Available Data aggregation has been considered as an effective way to decrease the data to be transferred in sensor networks. Particularly for wearable sensor systems, smaller battery has less energy, which makes energy conservation in data transmission more important. Nevertheless, wearable sensor systems usually have features like frequently dynamic changes of topologies and data over a large range, of which current aggregating methods can’t adapt to the demand. In this paper, we study the system composed of many wearable devices with sensors, such as the network of a tactical unit, and introduce an energy consumption-balanced method of data aggregation, named LDA-RT. In the proposed method, we develop a query algorithm based on the idea of ‘happened-before’ to construct a dynamic and energy-balancing routing tree. We also present a distributed data aggregating and sorting algorithm to execute top-k query and decrease the data that must be transferred among wearable devices. Combining these algorithms, LDA-RT tries to balance the energy consumptions for prolonging the lifetime of wearable sensor systems. Results of evaluation indicate that LDA-RT performs well in constructing routing trees and energy balances. It also outperforms the filter-based top-k monitoring approach in energy consumption, load balance, and the network’s lifetime, especially for highly dynamic data sources.

  12. Mesoscopic Simulation of Aggregates in Surfactant/Oil/Water Systems

    Institute of Scientific and Technical Information of China (English)

    苑世领; 蔡政亭; 徐桂英

    2003-01-01

    The aggregates in sodium dedecylsulphate(SDS)/dimethylbenzene/water systems have been investigated using dissipative particles dynamic(DPD) simulation method.Through analyzing three-dimensional structures of aggregates,three simulated results are found.One is the phase separation,which is clearly observed by water density and the aggregates in the simulated cell;another is the water morphology in reverse micelle,which can be found through the isodensity slice of water including bound water,trapped water and bulky water;the third is about the water/oil interface,i.e.,ionic surfactant molecules,SDS,prefer to exist in the interface between water and oil phase at the low concentraion.

  13. Power System Aggregate Load Area Modelling by Particle Swarm Optimization

    Institute of Scientific and Technical Information of China (English)

    Jian-Lin Wei; Ji-Hong Wang; Q.H.Wu; Nan Lu

    2005-01-01

    This paper presents a new approach for deriving a power system aggregate load area model (ALAM). In this approach, an equivalent area load model is derived to represent the load characters for a particular area load of a power system network. The Particle Swarm Optimization (PSO) method is employed to identify the unknown parameters of the generalised system, ALAM, based on the system measurement directly using a one-step scheme. Simulation studies are carried out for an IEEE 14-Bus power system and an IEEE 57-Bus power system. Simulation results show that the ALAM can represent the area load characters accurately under different operational conditions and at different power system states.

  14. Platelet Hyperactivity in TNFSF14/LIGHT Knockout Mouse Model of Impaired Healing.

    Science.gov (United States)

    Dhall, Sandeep; Karim, Zubair A; Khasawneh, Fadi T; Martins-Green, Manuela

    2016-10-01

    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.

  15. Reactivity, swelling and aggregation of mixed-size silicate nanoplatelets

    Science.gov (United States)

    Segad, M.; Cabane, B.; Jönsson, Bo

    2015-10-01

    Montmorillonite is a key ingredient in a number of technical applications. However, little is known regarding the microstructure and the forces between silicate platelets. The size of montmorillonite platelets from different natural sources can vary significantly. This has an influence on their swelling behavior in water as well as in salt solutions, particularly when tactoid formation occurs, that is when divalent counterions are present in the system. A tactoid consists of a limited number of platelets aggregated in a parallel arrangement with a constant separation. The tactoid size increases with platelet size and with very small nanoplatelets, ~30 nm, no tactoids are observed irrespectively of the platelet origin and concentration of divalent ions. The formation and dissociation of tactoids seem to be reversible processes. A large proportion of small nanoplatelets in a mixed-size system affects the tactoid formation, reduces the aggregation number and increases the extra-lamellar swelling in the system.

  16. [Changes in platelet function in children with acute or chronic tonsillitis].

    Science.gov (United States)

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

    2004-01-01

    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.

  17. 猪链球菌溶血素(SLY)引起血小板聚集活性分析%Activity identification of Streptococcus suis suilysin inducing platelets aggregation

    Institute of Scientific and Technical Information of China (English)

    张省委; 刘鹏; 徐茂凯; 尚学义; 郑玉玲; 袁媛; 姜永强

    2016-01-01

    目的:研究重组表达的2型猪链球菌溶血素( SLY)与血小板的相互作用,为临床猪链球菌感染的救治提供理论基础。方法镍柱亲和层析法纯化重组SLY蛋白,光密度法检测其溶血活性,再通过血小板聚集仪和扫描电子显微镜观察SLY蛋白与血小板的相互作用,并研究抗血小板药物阿司匹林对SLY引起的血小板聚集的影响,通过比较野生株05ZYH33和sly基因突变株Δsly对小鼠体内血小板体积和数量的影响,推测SLY蛋白对体内血小板的影响。结果与结论重组SLY蛋白溶血活性为2000 HU,1μg/ml SLY蛋白可引起血小板高度聚集,5 mmol/L阿司匹林可显著抑制聚集,SLY蛋白可引起小鼠体内单个血小板体积增大和血小板数量减少。%Objective To explore the interaction of streptococcus suis serotype 2 recombinant suilysin ( SLY ) with platelets, and provide the theoretical basis for clinic treatment of patients infected with S.suis.Methods The nickel column affinity chromatography was used to purify the recombinant SLY.The hemolytic acivity was identified by optical density before the platelets aggregation induced by a SLY was detected by a platelet aggregometer or electron microscope and the effect of aspirin on platelets aggregation was analyzed.The impact of wild type 05ZYH33 and sly-deficient mutant strainΔSLY on platelets of mice was compared to predict the interaction of the SLY with platelets in vivo.Results and Conclusion Hemolytic activity of recombinant SLY was 2000 hemolytic units( HU) and platelets aggregation was induced at 1 μg/ml.The aggregation can be inhibited by aspirin in 5 mmol/L.SLY can also increase the volume and reduce the amount of platelets in mice.

  18. 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

    2014-06-01

    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.

  19. Betaine (N,N,N-trimethylglycine) averts photochemically-induced thrombosis in pial microvessels in vivo and platelet aggregation in vitro.

    Science.gov (United States)

    Nemmar, Abderrahim; Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

    2015-07-01

    Betaine (N,N,N-trimethylglycine) is an important food component with established health benefits through its homocysteine-lowering effects, and is used to lower total homocysteine concentration in plasma of patients with homocystinuria. It is well established that hyperhomocysteinemia is an established risk factor for cardiovascular disease and stroke. However, the possible protective effect of betaine on coagulation events in vivo and in vitro has thus far not been studied. Betaine was given to mice at oral doses of either 10 mg/kg (n = 6) or 40 mg/kg (n = 6) for seven consecutive days, and control mice (n = 6) received water only. The thrombotic occlusion time in photochemically induced thrombosis in pial arterioles was significantly delayed in mice pretreated with betaine at doses of 10 mg/kg (P betaine. In vitro, in whole blood samples collected from untreated mice (n = 3-5), betaine (0.01-1 mg/mL) significantly reversed platelet aggregation induced by adenosine diphosphate (5 µM). The number of circulating platelets and plasma concentration of fibrinogen in vivo were not significantly affected by betaine pretreament compared with the control group. Lipid peroxidation (LPO) in mice pretreated with betaine was significantly reduced compared with the control group. Moreover, betaine (0.01-1 mg/mL) caused a dose-dependent and significant prolongation of PT (n = 5) and aPTT (n = 4-6). In conclusion, our data show that betaine protected against coagulation events in vivo and in vitro and decreased LPO in plasma.

  20. Experimental study on the anti-platelet aggregation and anti-coagulant activity of isoliensinine%异莲心碱抗血小板聚集和抗凝血作用

    Institute of Scientific and Technical Information of China (English)

    陈灵骏; 罗顺德

    2011-01-01

    目的:探讨异莲心碱(isoliensinine,IL)对大鼠体内血小板聚集和凝血功能的影响.方法:以二磷酸腺苷(ADP)诱导血小板聚集,采用比浊法观察IL对兔体内外血小板1,3,5 min聚集率和最大聚集率的影响,同时评价IL对大鼠凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)及凝血酶时间(TT)的影响.结果:IL4 mg·L-1和8 mg·L-1能显著抑制ADP诱导的兔体外血小板1,3,5 min聚集率和最大聚集率,其抑制率为14.4%和27.9%;IL5 mg·kg-1和10 mg·kg-1能显著抑制ADP诱导的兔体内血小板1,3,5 min聚集率和最大聚集率,其抑制率为20.0%和32.6%; IL能显著延长大鼠PT,APTT和TT.结论:IL具有对抗血小板聚集和凝血作用.%OBJECTIVE To investigate the inhibitory effects of isoliensinine on platelet aggregation in rabbits and coagulation function in rats. METHODS Inhibition rates of platelet aggregation for isoliensinine in vivo and vitro were determined by the model of platelet aggregation induced by adenosine diphosphate. The effects of isoliensinine were also evaluated on pro-thrombin time (PT) , activated partial thromboplastin time (APTT) and thrombin time (TT). RESULTS Isoliensinine inhibited platelet aggregation in vitro at the concentration of 4 and 8 mg·L-1 , inhibition rates were 14. 4% and 27. 9%. Isoliensinine inhibited platelet aggregation in vivo at the concentration of 5 and 10 mg·kg-1 , inhibition rates were 20. 0% and 32. 6%. Isoliensinine also markedly prolonged PT, APTT and TT also. CONCLUSION Isoliensinine exerted remarkable effects against platelet aggregation and coagulation in animal study.

  1. pH-responsive drug delivery system based on AIE luminogen functionalized layered zirconium phosphate nano-platelets

    Science.gov (United States)

    Li, Dongdong; Zhang, Yuping; Zhou, Bingbing

    2015-05-01

    Aggregation-induced emission (AIE) luminogen, quaternary tetraphenylethene cation (TPEN), was successfully incorporated into layered α-zirconium phosphate (α-ZrP) by using co-precipitation method to form inorganic-organic hybrid materials. The obtained materials show the characteristic hexagonal platelet shape with the interlayer distance did not reveal significant difference compared with pure α-ZrP. In addition, the obtained hybrid materials emit strong blue emission centered at 476 nm in aqueous media due to the electrostatic interactions of TPEN with the anionic framework of α-ZrP, which largely restrict their intramolecular rotation. More importantly, the materials provide a pH dependent release of doxorubicin (DOX), suggesting that AIE luminogen functionalized α-ZrP may be used as an imaging guided and pH-responsive delivery system for targeting therapy.

  2. Taoren-Honghua herb pair and its main components promoting blood circulation through influencing on hemorheology, plasma coagulation and platelet aggregation.

    Science.gov (United States)

    Liu, Li; Duan, Jin-ao; Tang, Yuping; Guo, Jianming; Yang, Nianyun; Ma, Hongyue; Shi, Xuqin

    2012-01-31

    Persicae Semen (Taoren) and Carthami Flos (Honghua) used in pair which is named as Taoren-Honghua (TH) herb pair has been used in traditional Chinese medicine (TCM) for promoting blood circulation to dissipate blood stasis for many years in China. This paper investigated the effects of TH and its main components amygdalin and hydroxysafflor yellow A (HSYA) on hemorheological disorders of blood stasis in rats. Rats were randomly divided into seven groups (control group, model group, TH group, amygdalin group, HSYA group, amygdalin+HSYA group, and aspirin group) with eight animals in each, whose gender was equally distributed throughout groups. All treatments were performed by gavage and administered seven times with an interval of 12h. After the fifth administration, the model rats except those in control group with blood stasis were established by being placed in ice-cold water during the interval between two injections of adrenaline hydrochloride (Adr); and blood samples were collected 30min after the last administration on the following day. TH could significantly decrease whole blood viscosity (WBV), plasma viscosity (PV) and packed cell volume (PCV). It also significantly prolonged thrombin time (TT) and thromboplastin time (APTT), increased prothrombin time (PT) and lowered fibrinogen content (FIB). HSYA which significantly decreased WBV and PV had no effect on plasma coagulation parameters. Amygdalin could significantly decrease PV, prolong APTT and decrease FIB, showing few effects on WBV. TH and its main components amygdalin and HSYA could significantly reduce platelet aggregation and protect vascular endothelial cells. Based on the above results, amygdalin and HSYA were responsible for the main curative effects of TH and usually had synergetic effects, such as decreasing PV and platelet aggregation percentage. The study may provide scientific information to further understanding of the mechanism(s) of TH and its main components in activating blood

  3. Platelet surface glutathione reductase-like activity.

    Science.gov (United States)

    Essex, David W; Li, Mengru; Feinman, Richard D; Miller, Anna

    2004-09-01

    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.

  4. Crosstalk between platelets and the complement system in immune protection and disease.

    Science.gov (United States)

    Verschoor, A; Langer, H F

    2013-11-01

    Platelets have a central function in repairing vascular damage and stopping acute blood loss. They are equally central to thrombus formation in cardiovascular diseases such as myocardial infarction and ischaemic stroke. Beyond these classical prothrombotic diseases, immune mediated pathologies such as haemolytic uraemic syndrome (HUS) or paroxysmal nocturnal haemoglobinuria (PNH) also feature an increased tendency to form thrombi in various tissues. It has become increasingly clear that the complement system, part of the innate immune system, has an important role in the pathophysiology of these diseases. Not only does complement influence prothrombotic disease, it is equally involved in idiopathic thrombocytopenic purpura (ITP), an autoimmune disease characterised by thrombocytopenia. Thus, there are complex interrelationships between the haemostatic and immune systems, and platelets and complement in particular. Not only does complement influence platelet diseases such as ITP, HUS and PNH, it also mediates interaction between microbes and platelets during systemic infection, influencing the course of infection and development of protective immunity. This review aims to provide an integrative overview of the mechanisms underlying the interactions between complement and platelets in health and disease.

  5. MECHANISM OF PRESERVING EFFECT OF APROTININ ON PLATELET FUNCTION DURING CARDIOPULMONARY BYPASS

    Institute of Scientific and Technical Information of China (English)

    黄惠民; 丁文祥; 苏肇伉; 张伟忠

    1992-01-01

    The deficiency of platelet function is the main defect of hemostatic mechanism during cardiopulmonary bypass (CPB), which attributed to the postoperative bleeding complication to a great extent. The proteinase inhibitor aprotinin was reported to have preserving effect on platelet adhesion during CPB. In this clinical reserch we found that CPB caused plasma alpha 2-antiplasmin decreasing, indicating the fibrinolytic system activation. Meanwhile, the ristocetin-induced aggregation declined to 39.6% and platelet GPIb decreased to 50% of preoperative value. However, by treatment with aprotinin, the plasma alpha 2-antiplasmin during CPB did not change, platelet aggregation was improved and platelet GPIb was preserved, and consequently resulted in a 46% lower blood loss postoperatively. These results confirmed that aprotinin could inhibit the fibrinolysis during CPB, and thus relieve the platelet damage and improve the postoperative hemostatic mechanism.

  6. Cisplatin triggers platelet activation.

    Science.gov (United States)

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

    2000-09-01

    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.

  7. Propranolol modifies platelet serotonergic mechanisms in rats.

    Science.gov (United States)

    Zółtowski, R; Pawlak, R; Matys, T; Pietraszek, M; Buczko, W

    2002-06-01

    Though the mechanisms for the vascular actions of vasodilatory beta-blockers are mostly determined, some of their interactions with monoaminergic systems are not elucidated. Because there are evidences supporting a possible involvement of serotonin (5-HT) in the actions of beta-blockers, we studied the effect of propranolol on peripheral serotonergic mechanisms in normotensive and Goldblatt two-kidney - one clip (2K1C) hypertensive rats. In both groups of animals propranolol decreased systolic blood pressure, significantly increased whole blood serotonin concentration and at the same time it decreased platelet serotonin level. The uptake of the amine by platelets from hypertensive animals was lower than that of normotensive animals and it was decreased by propranolol only in the latter. In both groups propranolol inhibited potentiation of ADP-induced platelet aggregation by serotonin. In conclusion, this study provides evidence that propranolol modifies platelet serotonergic mechanisms in normotensive and renal hypertensive rats.

  8. Higher levels of circulating monocyte-platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection.

    Science.gov (United States)

    Liang, Hua; Duan, Zhaojun; Li, Dan; Li, Dongliang; Wang, Zheng; Ren, Li; Shen, Tao; Shao, Yiming

    2015-07-01

    Increased levels of monocyte-platelet aggregates (MPAs) are reported to be highly correlated with cardiovascular events. In this study, the MPA levels in different monocyte subsets and the associations between MPA levels, HIV-1 viremia and monocyte activation were evaluated during HIV-1 infection. The results showed that the percentages of MPAs in all three monocyte subsets were higher in HIV-1-infected subjects than in healthy controls, and were associated with the plasma viral load in the non-classical and intermediate monocyte subsets. The plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads and negatively associated with CD4 counts. P-selectin glycoprotein ligand-1 (PSGL-1) was shown to be expressed at significantly lower levels on all three monocyte subsets and was negatively correlated with the sCD163 level. The MPA level was correlated with the levels of plasma sCD163 but negatively correlated with CD163 and PSGL-1 on all three monocyte subsets. An elevated immune activation status was correlated with increased MPA formation, underlying the potential interaction between monocyte activation and MPA formation. This interaction may be related to a higher thromboembolic risk in patients infected with HIV-1.Cellular & Molecular Immunology advance online publication, 11 August 2014; doi:10.1038/cmi.2014.66.

  9. Effects of green tea or Sasa quelpaertensis bamboo leaves on plasma and liver lipids, erythrocyte Na efflux, and platelet aggregation in ovariectomized rats.

    Science.gov (United States)

    Ryou, Sung Hee; Kang, Min Sook; Kim, Kyu Il; Kang, Young Hee; Kang, Jung Sook

    2012-04-01

    This study was conducted to investigate the effects of Sasa quelpaertensis bamboo and green tea on plasma and liver lipids, platelet aggregation, and erythrocyte membrane Na channels in ovariectomized (OVX) rats. Thirty female rats were OVX, and ten female rats were sham-operated at the age of 6 weeks. The rats were divided into four groups at the age of 10 weeks and fed the experiment diets: sham-control, OVX-control, OVX-bamboo leaves (10%), or OVX-green tea leaves (10%) for four weeks. Final body weight increased significantly in the OVX groups compared with that in the sham-control, whereas body weight in the OVX-green tea group decreased significantly compared with that in the OVX-control (P bamboo group (P bamboo and OVX-green tea groups compared with that in the OVX-control (P bamboo leaves groups recovered bone density to some extent. The results show that ovariectomy caused an increase in body weight and liver triglycerides, and that green tea was effective for lowering body weight and triglycerides in OVX rats. Ovariectomy induced an increase in Na efflux via Na-K ATPase and a decrease in Na efflux via Na-K cotransport. Furthermore, consumption of green tea and bamboo leaves affected Na efflux channels, controlling electrolyte and body water balance.

  10. Identification of the platelet ADP receptor targeted by antithrombotic drugs.

    Science.gov (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

    2001-01-11

    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.

  11. Effect of Acetic Acid and Low Molecular Weight Component of Mature Vinegar on Platelet Aggregation%醋酸及陈醋低分子量成分的抗血小板聚集活性

    Institute of Scientific and Technical Information of China (English)

    何璐薇; 李志敏; 孙严; 张艳艳; 范俊峰

    2012-01-01

    The effects of acetic acid and low molecular weight component of mature vinegar on platelet aggregation induced by arachidonic acid and collagen were assayed. Results showed that the maximal inhibition rate of acetic acid on platelet aggregation induced by collagen was 75. 95% and the minimum concentration of acetic acid which could inhibit the aggregation rate was 0. 05mol/L while the maximal inhibition rate of acetic acid on platelet aggregation induced by arachidonic acid was 83.62% and the minimum concentration acetic acid was 0. 01 mol/L Compared with the control group, acetic acid and low molecular weight component of mature vinegar independently inhibited the platelet aggregation induced by arachidonic acid and collagen obviously, and the effect of acetic acid on platelet aggregation induced by arachidonic acid was greater than collagen.%以食醋中的醋酸和陈醋低分子成分为研究对象,评价其对由花生四烯酸和胶原诱导的血小板聚集反应的影响。结果表明,醋酸对由胶原诱导的血小板聚集的最大抑制率为75.95%,能起到作用的最低醋酸浓度为0.05mol/L;醋酸对由花生四烯酸诱导的血小板聚集的最大抑制率为83.62%,能起到作用的最低醋酸浓度为0.01mol/L。与空白对照组相比,醋酸及陈醋低分子成分均对由花生四烯酸和胶原诱导的血小板聚集有明显抑制作用,且抑制作用均呈浓度依赖型,其中醋酸对以花生四烯酸为诱导剂引起的血小板聚集的作用更为明显。

  12. 血小板聚集影响因素在血细胞计数中的临床应用%Clinical application of platelet aggregation for white blood cell count

    Institute of Scientific and Technical Information of China (English)

    胡恩亮; 赵媛; 王妍; 樊爱琳; 郑善銮

    2016-01-01

    Objective To analyze the cause of platelet aggregation in blood specimens ,so as to provide basis for reducing platelet aggregation ,and avoiding false positive of platelet count ,false report ,misdiagnosis and mistreatment .Methods The blood speci-mens which platelet was below 80 × 109 /L ,below 125 × 109 /L with histogram hinted platelet aggregation ,were smeared ,stained with Wright-Giemsa ,and observed by microscope for platelet morphological changes .The data between each groups were calculated and analyzed by statistical software SPSS version 18 .0 .Results A total of 184 cases of ethylenediaminetetraacetic acid dependent pseudothrombocytopenia(EDTA-PTCP) were found ,accounted for 0 .444 ‰ totally ,including 0 .244 ‰ of out-patients (101 cases) , 0 .159 ‰ of hospitalized patients (66 cases) ,and 0 .041 ‰ of health examination personnel (17 cases) .3 cases of multi-dependent pseudothrombocytopenia and 25 cases of pseudo platelet aggregation were found ,and accounted for 0 .007 ‰ and 0 .060 ‰ respec-tively .Conclusion The discovery of platelet aggregation which caused mainly by EDTA-PTCP ,still relies on microscopy ,and pseu-do platelet aggregation comes mainly from sampling ,so it needs to strengthen the skills training .%目的:分析血小板聚集影响因素,为降低血小板聚集所致血小板假性减低、实验室规避报告风险及减低误诊误治提供依据。方法对血小板小于80×109/L 、小于125×109/L 合并直方图提示血小板凝集标本进行推片、瑞氏-吉姆萨染色后显微镜下观察是否聚集,并采用统计软件 SPSS 18.0进行统计分析。结果乙二胺四乙酸依赖性血小板减少症(EDTA-PTCP)共计184例,占0.444‰,其中门诊患者101例,占0.244‰,住院患者66例,占0.159‰,体检者17例,占0.041‰;多重抗凝剂依赖性血小板假性减少共计3例,占0.007‰,假性血小板聚集共计25例,占0.060‰。结论血小

  13. Characterization of core/shell Cu/Ag nanopowders synthesized by electrochemistry and assessment of their impact on hemolysis, platelet aggregation, and coagulation on human blood for potential wound dressing use

    Science.gov (United States)

    Laloy, Julie; Haguet, Hélène; Alpan, Lutfiye; Mancier, Valérie; Mejia, Jorge; Levi, Samuel; Dogné, Jean-Michel; Lucas, Stéphane; Rousse, Céline; Fricoteaux, Patrick

    2017-08-01

    Copper/silver core/shell nanopowders with different metal ratio have been elaborated by electrochemistry (ultrasound-assisted electrolysis followed by a displacement reaction). Characterization was performed by several methods (X-ray diffraction, scanning electron microscope, energy-dispersive X-ray spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, centrifugal liquid sedimentation, and zeta potential measurements). The mean diameter of all nanoparticles is around 10 nm. The impact of each nanopowder on hemolysis, platelet aggregation, and coagulation has been studied on whole human blood. Hemolysis assays were performed with spectrophotometric measurement and platelet aggregation, with light transmission aggregometry and was compared to Cu/Pt core/shell nanoparticles with similar size as negative control. Calibrated thrombin generation test has been used for a coagulation study. They neither impact platelet aggregation nor hemolysis and have a procoagulant effect whatever their composition (i.e., metal ratio). These results highlight that such nanopowders have a potential use in medical applications (e.g., wound dressing).

  14. 根据生物学变异度确定血液学检测下限的研究%Use biological variation to value the lower detect limit of hematology and platelet aggregation test

    Institute of Scientific and Technical Information of China (English)

    吴俊; 赵洁; 宋英; 赵磊; 赵京忠

    2013-01-01

    目的 确定血常规分析,血小板聚集检验最低检测下限范围.方法 Sysmex2100血液分析仪检测血常规,将标本倍比稀释后重复检测10次样本,计算变异系数CV值,做曲线及计算方程,以1/2生物变异度规定为允许CV值,该CV值代入方程为检测低限.对于血小板聚集,稀释后检测血小板聚集,在低于平台区的范围定位检测下限.结果 白细胞检测下限为0.11×109/l,红细胞检测下限为0.14×1012/l,红细胞压积检测下限3.03%,血小板检测下限为15.31×109/l.血小板聚集需要最低的血小板数量为200×109/l.结论 以生物变异度为基础的CV来确认仪器检测下限,方法可行,且与临床实际情况相符合.可作为确定仪器检测下限的方法.%Objective To detect the lower limit of hematology,platelet aggregation. Methods we use sysmex 2100 hematology analyzer blood cell account;Chrono-log platelet function instrument test platelet aggregation rate. After di luting samples,we retest the sample 10 times, plot X-axis with concentration, Y-axis with CV%, calculated the equa tion. We set 1/2 biological variation as standard CV to get the lower limit of detection. As for platelet aggregation, the concentration below the plateau is the lower limit concentration. Results Low limit detection of white blood cell, red blood cell,hematocrit,platelet is 0.11 ×109/1,0.14 × 1012/1,3.03% ,15.31 × 109/1, respectivly. The low concentration of platelet aggregation is 200×109/1. Conclusion Use biological variation to set the lower limit of detection is practica ble. It fit with clinical situation. The 1/2 biological variation could be the standard of lower limit of detection evaluation.

  15. The biology of the platelet with special reference to inflammation, wound healing and immunity.

    Science.gov (United States)

    Nurden, Alan T

    2018-01-01

    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.

  16. In vitro function of random donor platelets stored for 7 days in composol platelet additive solution

    Directory of Open Access Journals (Sweden)

    Gupta Ashish

    2011-01-01

    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.

  17. Stimulation of Toll-like receptor 2 in human platelets induces a thromboinflammatory response through activation of phosphoinositide 3-kinase.

    Science.gov (United States)

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

    2009-02-13

    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.

  18. Organic Aggregation of Knowledge Object in Educational Systems

    Directory of Open Access Journals (Sweden)

    Gilbert Paquette

    2002-10-01

    Full Text Available We propose an organic approach to educational web-based systems where learning objects, operations on these objects, and actors that perform them are aggregated in meaningful ways. The users of a learning system must be able to observe it globally, at different levels and from diverse viewpoints. They must be able to propose adaptations and improvements constantly using means of observation integrated with the means of action. For this, we need to provide inspectable and executable models of the learning system, to be used as prisms for understanding and control of operations. We propose to reference these models with educational ontologies developed for instructional engineering. The implementation of some of these ideas in the Explor@-II system provides examples. Conversely, the next Explor@ implementation will benefit from the discussion presented here.

  19. Equine autologous platelet concentrates : A comparative study between different available systems

    NARCIS (Netherlands)

    Hessel, L N; Bosch, G; van Weeren, P R; Ionita, J-C

    2015-01-01

    REASONS FOR PERFORMING STUDY: Autologous platelet concentrates (APCs) are being used increasingly in horses to enhance regeneration in tissues that have poor natural healing capabilities. Numerous APC systems, which are based on different preparation techniques and were originally developed for huma

  20. Research Influence Biological Active Agents in the Course of Regulation of Functional Activity of Platelets and System of a Haemostasis

    Directory of Open Access Journals (Sweden)

    Nozim N. Khoshimov

    2015-06-01

    Full Text Available It is shown that the flavonoid pulikarin suppresses activity of an adenylate cyclase and reduces level intracellular [Ca2+], perhaps its effect is connected with inhibition of a gain of cytoplasmatic Ca2+ as at the expense of its entrance outside, and release from intracellular storages. Perhaps, oppression of fluorescence of membrane-bound Ca2+ is connected with inhibition of a pulikarin of release of calcium from intracellular depots. The inhibiting effect of a pulikarin on ADP-induced aggregation of platelets is connected with oppression of a gain of cytoplasmatic concentration of Ca2+ from depot of platelets.

  1. Comparative evaluation of platelet-rich fibrin, mineral trioxide aggregate, and calcium hydroxide as pulpotomy agents in permanent molars with irreversible pulpitis: A randomized controlled trial

    Science.gov (United States)

    Kumar, Varun; Juneja, Ruchi; Duhan, Jigyasa; Sangwan, Pankaj; Tewari, Sanjay

    2016-01-01

    Background: Pulpotomy has been proposed as an alternative for the management of irreversible pulpitis in permanent molars with closed apices. Aim: To compare the performances of calcium hydroxide (CH), mineral trioxide aggregate (MTA), and platelet-rich fibrin (PRF) as pulpotomy agents in mature permanent molars with irreversible pulpitis. Materials and Methods: Fifty-four permanent mandibular molars with carious exposure and symptoms of irreversible pulpitis were randomly allocated to three groups, and full pulpotomy was performed using CH, MTA, or PRF as pulpotomy agents. Pain intensity was recorded using numeric rating scale score at baseline, 24 h, 7 days, 6 months, and 1 year. Clinical and radiographic assessments were done at 6 months and 1 year. Statistical Analysis: Kruskal–Wallis test and Friedman test were used for intergroup and intragroup comparison of pain scores, respectively. The radiographic outcomes between the three study arms were compared using Chi-square test. Results: Clinical success rate was 94.4% at 7 days, which dropped to 85.4% at 12 months. All three agents were equally effective in providing pain relief at all the intervals tested, with no significant difference between them (P > 0.05 at all intervals). However, at 6 months and 12 months, 26.2% and 52.4% teeth depicted slight widening of periodontal ligament space. No significant difference was observed between the radiographic success rates observed with the three groups (P = 0.135 at 6 months, 0.717 at 12 months). Conclusion: Pulpotomy exhibited a high clinical success rate in mature molars with irreversible pulpitis and selection of biomaterial did not affect its outcome. PMID:27994420

  2. Immunohistochemical Evaluation of Fibronectin and Tenascin Following Direct Pulp Capping with Mineral Trioxide Aggregate, Platelet-Rich Plasma and Propolis in Dogs’ Teeth

    Science.gov (United States)

    Moradi, Saeed; Saghravanian, Nasrollah; Moushekhian, Siavash; Fatemi, Samar; Forghani, Maryam

    2015-01-01

    Introduction: The aim of the present study was to evaluate the expression of fibronectin (FN) and tenascin (TN) after direct pulp capping (DPC) in dogs’ teeth with either mineral trioxide aggregate (MTA), Propolis or Platelet-rich plasma (PRP), by means of immunohistochemistry. Methods and Materials: A total of 48 sound molars and premolars with mature apices from four dogs, were included. The teeth were randomly divided into 4 groups according to the material used for DPC: PRP, Propolis, MTA, and glass-ionomer (as the negative control group). Each group was divided into two 7-day and 30-day subgroups. The teeth were restored at the same session. The animals were sacrificed at the mentioned time intervals and the expression of FN and TN in each test group and between each time intervals was assessed with Wilcoxon and Mann-Whitney U tests, respectively. The Kruskal-Wallis test was used to compare FN and TN staining among the test groups. The significance level was set at 0.05. Results: The amount of FN in the MTA group in the 30-day interval was significantly higher than the 7-day interval; however, there were no significant differences among the other groups. The amount of TN in the MTA and Propolis groups in the 30-day interval was significantly higher than that in the 7-day interval; no recognizable difference was observed in the other groups. Moreover, the difference in expression of FN and TN in the 7-day interval was not significant in the experimental groups. Nevertheless, the difference was significant in the 30-day interval, with the highest and lowest expressions belonging to the MTA and glass-ionomer groups, respectively. Conclusion: Based on the results of the present animal study, MTA is still a better choice for direct pulp capping PMID:26213542

  3. Comparative evaluation of platelet-rich fibrin, mineral trioxide aggregate, and calcium hydroxide as pulpotomy agents in permanent molars with irreversible pulpitis: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Varun Kumar

    2016-01-01

    Full Text Available Background: Pulpotomy has been proposed as an alternative for the management of irreversible pulpitis in permanent molars with closed apices. Aim: To compare the performances of calcium hydroxide (CH, mineral trioxide aggregate (MTA, and platelet-rich fibrin (PRF as pulpotomy agents in mature permanent molars with irreversible pulpitis. Materials and Methods: Fifty-four permanent mandibular molars with carious exposure and symptoms of irreversible pulpitis were randomly allocated to three groups, and full pulpotomy was performed using CH,MTA, or PRF as pulpotomy agents. Pain intensity was recorded using numeric rating scale score at baseline, 24 h, 7 days, 6 months, and 1 year. Clinical and radiographic assessments were done at 6 months and 1 year. Statistical Analysis: Kruskal–Wallis test and Friedman test were used for intergroup and intragroup comparison of pain scores, respectively. The radiographic outcomes between the three study arms were compared using Chi-square test. Results: Clinical success rate was 94.4% at 7 days, which dropped to 85.4% at 12 months. All three agents were equally effective in providing pain relief at all the intervals tested, with no significant difference between them (P > 0.05 at all intervals. However, at 6 months and 12 months, 26.2% and 52.4% teeth depicted slight widening of periodontal ligament space. No significant difference was observed between the radiographic success rates observed with the three groups (P = 0.135 at 6 months, 0.717 at 12 months. Conclusion: Pulpotomy exhibited a high clinical success rate in mature molars with irreversible pulpitis and selection of biomaterial did not affect its outcome.

  4. The ultrastructure of camel blood platelets: a comparative study with human, bovine, and equine cells.

    Science.gov (United States)

    Gader, Abdel Galil M Abdel; Ghumlas, Abeer K Al; Hussain, Mansour F; Haidari, Ahmed Al; White, James G

    2008-02-01

    Previous studies indicated that the camel has a very active haemostatic mechanism with a short bleeding time and thrombocytosis. However, platelet function, when tested by agonist-induced aggregation and PFA 100 closure time, showed marked inhibition compared to humans. Since camels are also far more resistant to long exposure to excessive heat and high body temperature than humans, it seemed worthwhile to explore fundamental morphological differences between human and camel platelets and those from other species. The present study has examined the ultrastructure of camel platelets and compared them with the fine structures of human, bovine and equine thrombocytes. Camel platelets, like bovine and equine cells, are discoid in shape and about two-thirds the size of human platelets. A circumferential coil of microtubular supports the disk-like form of camel platelets. Their cytoplasm, like bovine and equine platelets, is filled with alpha granule twice as large as those in human platelets, but lacking the organized matrix of equine alpha granules. Dense bodies are present in camel platelets with whip-like extensions not present on bovine or equine thrombocytes, but found on occasional human platelet dense bodies. Camel platelets, like bovine and equine thrombocytes, lack an open canalicular system (OCS) and must secrete granule products by fusion with the cell wall rather than an OCS. Future studies will determine if the differences in ultrastructural anatomy protect camel platelets from heat more than human thrombocytes.

  5. Effect of ionizing radiation on platelet function in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kalovidouris, A.E.; Papayannis, A.G. (Evangelismos Hospital, Athens (Greece))

    1981-01-01

    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 ..mu..mol 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.

  6. 山绿茶提取物对体外人血小板聚集的影响%Effect of Extracts from Ilex Hainanensis Merr.on Human Platelet Aggregation in Vitro

    Institute of Scientific and Technical Information of China (English)

    李浩野; 孟兰贞; 黄卫华; 赵静; 刘华钢; 李绍平

    2013-01-01

    山绿茶为广西少数民族民间中草药,具有活血通脉等治疗心血管疾病的功效.为观察山绿茶提取物对花生四烯酸钠盐(AA)、二磷酸腺苷(ADP)、盐酸肾上腺素(ADR)诱导的体外人血小板聚集的影响,通过阿司匹林为阳性药建立体外抗人血小板聚集模型,以健康人富血小板血浆为研究对象,分别以AA、ADP、ADR作为诱导剂,运用Born氏比浊法测定体外诱导的人血小板聚集率,探究不同山绿茶提取物对体外诱导的人抗血小板聚集的影响.实验结果表明:阳性药阿司匹林对诱导的体外人血小板聚集有明显抑制作用,而山绿茶各提取物对诱导的体外人血小板聚集无显著影响,虽然山绿茶提取物对体外人血小板聚集的抑制作用为阴性结果,但为地方中药材标准的完善提供了实验依据.%Ilex hainanensis Merr is the national minority folk herbal medicine in the Guangxi Zhuang Autonomous Region,and its effects of blood invigorate and pulse promotion can provide potential therapeutic approaches to treatment cardiovascular diseases.The aim of this paper is to observe the effect of different extracts from Ilex hainanensis Merr (IHE) on human platelet aggregation induced by arachidonic acid sodium salt (AA),adenosine diphosphate (ADP),and epinephrine hydrochlaride (ADR),respectively,in vitro.In this study,aspirin was used as positive control drug to establish the in vitro anti-platelet aggregation model and platelet aggregation rate was measured by Born's method.Platelet-rich plasma was collected from healthy donors and induced by AA,ADP and ADR,respectively and the model was applied to study the effect of different IHE on the platelet aggregation.The results showed that aspirin can significantly inhibit platelet aggregation induced by AA,ADP and ADR in vitro,respectively,but the IHE did not show inhibiting effect on the human platelet aggregation significantly.However,the IHE negative results can provide solid

  7. Soil Aggregate Stability and Aggregate-Associated Carbon Under Different Tillage Systems in the North China Plain

    Institute of Scientific and Technical Information of China (English)

    DU Zhang-liu; REN Tu-sheng; HU Chun-sheng; ZHANG Qing-zhong; Humberto Blanco-Canqui

    2013-01-01

    The inlfuences of tillage systems on soil carbon (C) stocks have been studied extensively, but the distribution of soil C within aggregate fractions is not well understood. The objective of this study was to determine the inlfuences of various tillage systems on soil aggregation and aggregate-associated C under wheat (Triticum aestivum L.) and corn (Zea mays L.) double cropping systems in the North China Plain. The experiment was established in 2001, including four treatments:moldboard plow (MP) with residue (MP+R) and without residue (MP-R), rotary tillage with residue (RT), and no-till with residue (NT). In 2007 soil samples were collected from the 0-5, 5-10, and 10-20 cm depths, and were separated into four aggregate-size classes (>2 000, 250-2 000, 53-250, and2 000 and 250-2 000 µm) compared with the MP-R and MP+R treatments. Averaged across all depths, mean weight diameters of aggregates (MWD) in NT and RT were 47 and 20% higher than that in MP+R. The concentration of bulk soil organic C was positively correlated with MWD (r=0.98; P=0.024) and macroaggregate fraction (r=0.96; P=0.036) in the 0-5 cm depth. In the 0-20 cm depth, comparing with MP+R, total C occluded in the>2 000 µm fraction was increased by 9 and 6%under NT and RT, respectively. We conclude that adoption of conservation tillage system, especially no-till, can increase soil macro-aggregation and total C accumulation in macroaggregates, which may improve soil C sequestration in the intensive agricultural region of the North China Plain.

  8. STABILIZATION OF STANDARD PLATELET CONCENTRATES AND MINIMIZATION OF THE PLATELET STORAGE LESION BY A PROSTACYCLIN ANALOG

    NARCIS (Netherlands)

    ELIAS, M; HEETHUIS, A; BOM, [No Value; BLOM, N; MCSHINE, RL; HALIE, MR; SIBINGA, CTS

    Platelet concentrates were pretreated with a stable synthetic prostacyclin analogue (Iloprost) at two different concentrations before the second centrifugation step (pelleting step) of preparation. This resulted in loss. of platelet sensitivity to aggregating agents. To mimic the situation after

  9. Alloimmune refractoriness to platelet transfusions.

    Science.gov (United States)

    Sandler, S G

    1997-11-01

    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).

  10. Platelet function in dogs

    DEFF Research Database (Denmark)

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

    2007-01-01

    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...

  11. Platelet function in dogs

    DEFF Research Database (Denmark)

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

    2007-01-01

    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....

  12. A net-jet flow system for mass transfer and microsensor studies of sinking aggregates

    DEFF Research Database (Denmark)

    Ploug, H.; Jørgensen, BB

    1999-01-01

    was shown to be laminar at flow velocities ranging from 40 to 200 m d(-1), which cover typical sinking velocities of aggregates in the ocean. A viscous boundary layer with steep gradients of flow velocity was measured around sinking aggregates by flow visualization techniques. Velocity gradients......A flow system was developed which enables studies of hydrodynamics and mass transfer in freely sinking aggregates. The aggregates stabilized their positions in the water phase at an upward flow Velocity which balanced and opposed the sinking velocity of the individual aggregate. The flow field...... in the viscous boundary layer along the sides of the aggregate parallel to the flow could by explained by creeping flow, while a non-turbulent wake was present at the rear (downstream) of the aggregate. The oxygen distribution inside a ca 3.5 mm large diatom aggregate and in the surrounding water was mapped in 2...

  13. A Multiagent System for Dynamic Data Aggregation in Medical Research

    Science.gov (United States)

    Urovi, Visara; Barba, Imanol; Aberer, Karl; Schumacher, Michael Ignaz

    2016-01-01

    The collection of medical data for research purposes is a challenging and long-lasting process. In an effort to accelerate and facilitate this process we propose a new framework for dynamic aggregation of medical data from distributed sources. We use agent-based coordination between medical and research institutions. Our system employs principles of peer-to-peer network organization and coordination models to search over already constructed distributed databases and to identify the potential contributors when a new database has to be built. Our framework takes into account both the requirements of a research study and current data availability. This leads to better definition of database characteristics such as schema, content, and privacy parameters. We show that this approach enables a more efficient way to collect data for medical research. PMID:27975063

  14. A Multiagent System for Dynamic Data Aggregation in Medical Research

    Directory of Open Access Journals (Sweden)

    Alevtina Dubovitskaya

    2016-01-01

    Full Text Available The collection of medical data for research purposes is a challenging and long-lasting process. In an effort to accelerate and facilitate this process we propose a new framework for dynamic aggregation of medical data from distributed sources. We use agent-based coordination between medical and research institutions. Our system employs principles of peer-to-peer network organization and coordination models to search over already constructed distributed databases and to identify the potential contributors when a new database has to be built. Our framework takes into account both the requirements of a research study and current data availability. This leads to better definition of database characteristics such as schema, content, and privacy parameters. We show that this approach enables a more efficient way to collect data for medical research.

  15. The role of platelets in hemostasis and the effects of snake venom toxins on platelet function.

    Science.gov (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

    2017-07-01

    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.

  16. Decreased TGF-β1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis

    Science.gov (United States)

    Maloney, James P.; Narasimhan, Jayashree; Biller, Julie

    2016-01-01

    Purpose Cystic fibrosis (CF) patients suffer from chronic lung inflammation. This inflammation may activate platelets. There are limited data on the role of platelet-secreted cytokines in CF. Platelet cytokines with inflammatory effects include vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). As levels of these cytokines are tenfold greater in serum than plasma due to platelet release, serum levels may be one index of platelet content; but a more specific index is release during the aggregation of isolated platelets. We postulated that altered release of these platelet cytokines occurs in CF. Methods We obtained sera and plasma from CF outpatients (n=21) and from healthy controls (n=20), measured VEGF and TGF-β1, assessed for correlations with platelet number, analyzed cytokine release during platelet aggregation to collagen, and analyzed differences in maximal platelet aggregation. Results Platelet number and maximal aggregation levels were higher in CF. Plasma and serum levels of TGF-β1 and VEGF were higher in CF, but these levels were similar after adjusting for platelet number (serum cytokines correlated with platelet count). The release of VEGF and TGF-β1 during aggregation was decreased in CF platelets (by 52% and 29%, respectively). Conclusion Platelet release is not a source of the elevated blood proinflammatory cytokines TGF-β1 and VEGF in CF, as platelets from CF patients actually release less of these cytokines. These data provide further evidence for platelet defects in CF. PMID:27423781

  17. Estrogen, inflammation, and platelet phenotype.

    Science.gov (United States)

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

    2008-01-01

    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.

  18. Variation in dietary salt intake induces coordinated dynamics of monocyte subsets and monocyte-platelet aggregates in humans: implications in end organ inflammation.

    Directory of Open Access Journals (Sweden)

    Xin Zhou

    Full Text Available BACKGROUND: Monocyte activation and tissue infiltration are quantitatively associated with high-salt intake induced target organ inflammation. We hypothesized that high-salt challenge would induce the expansion of CD14++CD16+ monocytes, one of the three monocyte subsets with a pro-inflammatory phenotype, that is associated with target organ inflammation in humans. METHODOLOGY/PRINCIPAL FINDINGS: A dietary intervention study was performed in 20 healthy volunteers, starting with a 3-day usual diet and followed with a 7-day high-salt diet (≥15 g NaCl/day, and a 7-day low-salt diet (≤5 g NaCl/day. The amounts of three monocyte subsets ("classical" CD14++CD16-, "intermediate" CD14++CD16+ and "non-classical" CD14+CD16++ and their associations with monocyte-platelet aggregates (MPAs were measured by flow cytometry. Blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI was used to evaluate renal hypoxia. Switching to a high-salt diet resulted in CD14++ monocyte activation and a rapid expansion of CD14++CD16+ subset and MPAs, with a reciprocal decrease in the percentages of CD14++CD16- and CD14+CD16++ subsets. In vitro study using purified CD14++ monocytes revealed that elevation in extracellular [Na(+] could lead to CD14++CD16+ expansion via a ROS dependent manner. In addition, high-salt intake was associated with progressive hypoxia in the renal medulla (increased R2* signal and enhanced urinary monocyte chemoattractant protein-1 (MCP-1 excretion, indicating a temporal and spatial correlation between CD14++CD16+ subset and renal inflammation. The above changes could be completely reversed by a low-salt diet, whereas blood pressure levels remained unchanged during dietary intervention. CONCLUSIONS/SIGNIFICANCE: The present work demonstrates that short-term increases in dietary salt intake could induce the expansion of CD14++CD16+ monocytes, as well as an elevation of MPAs, which might be the underlying cellular basis of high-salt induced

  19. Systemic effects of locally injected platelet rich plasma in a rat model: an analysis on muscle and bloodstream.

    Science.gov (United States)

    Borrione, P; Grasso, L; Racca, S; Abbadessa, G; Carriero, V; Fagnani, F; Quaranta, F; Pigozzi, F

    2015-01-01

    Abundant evidence suggests that growth factors, contained in platelets alpha granules, may play a key role in the early stages of the muscle healing process with particular regard to the inflammatory phase. Although the contents of the platelet-rich plasma preparations have been extensively studied, the biological mechanisms involved as well as the systemic effects and the related potential doping implications of this approach are still largely unknown. The aim of the present study was to investigate whether local platelet-rich plasma administration may modify the levels of specific cytokines and growth factors both in treated muscle and bloodstream in rats. An additional aim was to investigate more deeply whether the local platelet-rich plasma administration may exert systemic effects by analyzing contralateral lesioned but untreated muscles. The results showed that platelet-rich plasma treatment induced a modification of certain cytokines and growth factor levels in muscle but not in the bloodstream, suggesting that local platelet-rich plasma treatment influenced directly or, more plausibly, indirectly the synthesis or recruitment of cytokines and growth factors at the site of injury. Moreover, the observed modifications of cytokine and growth factor levels in contralateral injured but not treated muscles, strongly suggested a systemic effect of locally injected platelet-rich plasma.

  20. Physiopathology of blood platelets: a model system for studies of cell-to-cell interaction. Progress report, November 1, 1979-October 31, 1980

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-01-01

    This report covers the studies on basic mechanisms of cellular interactions, utilizing platelets as a model system and, when possible, concentrating on the influence that environmental factors (nutritional, metabolic, cellular, immunologic and others) have on them. The four major sections include: platelet interaction with tumor cells; a model for the study of cell-to-cell interaction; interaction of platelets with vessel walls; and platelet interactions with immune proteins.

  1. Effects on platelets and on the clotting system of four glycosaminoglycans extracted from hog mucosa and one extracted from aortic intima of the calf.

    Science.gov (United States)

    Cella, G; Scattolo, N; Luzzatto, G; Stevanato, F; Vio, C; Girolami, A

    1986-01-01

    A commercial heparin preparation, a heparin fraction with a molecular weight of 12,000 Daltons, heparan sulfate, dermatan sulfate obtained from hog mucosa, and mesoglycan, an heparinoid obtained from calf aortic intima were investigated. Commercial mucous heparin had a stimulatory effect on platelet aggregation induced by ADP, while the others failed to do so. Dermatan sulfate had a dose dependent inhibition and commercial mucosal heparin, a dose dependent stimulation, on serotonin release induced by ADP. Both the commercial mucosal heparin and dermatan sulfate showed an inhibition and the other glycosaminoglycans (GAGs) a negligible effect on collagen induced platelet aggregation. The collagen induced serotonin release was clearly reduced by all GAGs; heparan sulfate had this activity only at the highest doses used. Commercial mucosal heparin produced the highest activity on clotting systems as measured by activated partial thromboplastin time, while mesoglycan had the strongest anti-factor Xa specific activity as measured by a clotting assay. Dermatan sulfate was the weakest on both assays. When we injected intravenously an equivalent amount (about 60 mg) of heparin fraction, heparan sulfate, dermatan sulfate and mesoglycan in three different volunteers with an interval of 20 days after each injection, we had an immediate platelet factor 4 (PF4) release only with heparin fraction, heparan sulfate and mesoglycan. Heparin fraction and mesoglycan, in spite of having a wide discrepancy in anticoagulant effect, caused almost the same PF4 release. GAGs which can neutralize PF4 and which can also have specific anti-factor Xa activity could represent a great advantage in thrombosis prophylaxis.

  2. Multiple discrete soluble aggregates influence polyglutamine toxicity in a Huntington’s disease model system

    Science.gov (United States)

    Xi, Wen; Wang, Xin; Laue, Thomas M.; Denis, Clyde L.

    2016-01-01

    Huntington’s disease (HD) results from expansions of polyglutamine stretches (polyQ) in the huntingtin protein (Htt) that promote protein aggregation, neurodegeneration, and death. Since the diversity and sizes of the soluble Htt-polyQ aggregates that have been linked to cytotoxicity are unknown, we investigated soluble Htt-polyQ aggregates using analytical ultracentrifugation. Soon after induction in a yeast HD model system, non-toxic Htt-25Q and cytotoxic Htt-103Q both formed soluble aggregates 29S to 200S in size. Because current models indicate that Htt-25Q does not form soluble aggregates, reevaluation of previous studies may be necessary. Only Htt-103Q aggregation behavior changed, however, with time. At 6 hr mid-sized aggregates (33S to 84S) and large aggregates (greater than 100S) became present while at 24 hr primarily only mid-sized aggregates (20S to 80S) existed. Multiple factors that decreased cytotoxicity of Htt-103Q (changing the length of or sequences adjacent to the polyQ, altering ploidy or chaperone dosage, or deleting anti-aging factors) altered the Htt-103Q aggregation pattern in which the suite of mid-sized aggregates at 6 hr were most correlative with cytotoxicity. Hence, the amelioration of HD and other neurodegenerative diseases may require increased attention to and discrimination of the dynamic alterations in soluble aggregation processes. PMID:27721444

  3. SYSTEM AGGREGATION METHOD FOR FAILURE PRONE PRODUCTION LINES WITH UNRELIABLE LIMITED BUFFERS

    Institute of Scientific and Technical Information of China (English)

    LIU Jun; RUI Zhiyuan; ZHAO Juntian; WEI Yaobing

    2008-01-01

    Different from traditional aggregation method, the unreliable buffers are originally considered and a more general aggregation method is offered, in which not only the unreliable buffers are considered, but also the probabilities of system states are obtained by a discrete model rather than the continuous flow model of unreliable manufacturing systems. The solution technique is offered to get the system sate probabilities. The method advances the traditional system aggregation techniques. Numerical results specify the extended aggregation method and also show that the unreliable limited buffers have a strong impact on the efficiency of the production lines.

  4. No evidence for a putative involvement of platelet-activating factor in systemic lupus erythematosus without active nephritis

    Directory of Open Access Journals (Sweden)

    Yves Denizot

    2003-01-01

    Full Text Available Background: Platelet-activating factor (PAF seems to be implicated in systemic lupus erythematosus (SLE patients with associated renal diseases.Aims: In this study, we ensured the role of PAF in SLE patients without renal complications.

  5. Effects of Nd:YAG laser-heated metal cap on human platelets in vitro

    Science.gov (United States)

    Liu, Xia; Guo, You-chi

    1993-03-01

    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.

  6. Platelet membrane glycoproteins and their function: an overview.

    Science.gov (United States)

    Kunicki, T J

    1989-07-01

    The membrane glycoproteins (GP) of human platelets act as receptors that mediate two important functions, adhesion to the subendothelial matrix and platelet-platelet cohesion, or aggregation. Many of these glycoprotein receptors exist as noncovalently linked heterodimers, including those that belong to the supergene family of adhesion receptors called the integrins. Human platelets contain at least five members of this integrin family, including a collagen receptor (GP Ia-IIa; alpha 2, beta 1), a fibronectin receptor (GP Ic-IIa; alpha 5, beta 1), a laminin receptor (GP Ic'-IIa; alpha 6, beta 1), a vitronectin receptor (VnR; alpha v, beta 3), and a promiscuous, activation-dependent receptor that is thought to be the receptor most responsible for fibrinogen-dependent, platelet-platelet cohesion (GP IIb-IIIa; alpha IIb, beta 3). Some, but not all, of the integrins bind to a tripeptide sequence, arginine-glycine-aspartic acid (RGD), on the adhesive proteins. In addition to the integrins, platelets contain other membrane glyco-proteins: GP Ib-IX, a receptor for von Willebrand factor, which is thought to be the receptor most responsible for platelet adhesion to the subendothelial matrix in a flowing system; GP V, which may be associated with GP Ib-IX and whose function remains unknown; and GP IV (GP IIIb), which functions as a receptor for thrombospondin and collagen.

  7. The role of a platelet Lysate-Based compartmentalized system as a carrier of cells and platelet-origin cytokines for periodontal tissue regeneration

    OpenAIRE

    Babo, Pedro Miguel Sousa; Xinjie Cai; Plachokova, A.; Reis, R. L.; Jansen, John A.; Gomes, Manuela E.; Walboomers, X. Frank

    2016-01-01

    Currently available clinical therapies are not capable to regenerate tissues that are lost by periodontitis. Tissue engineering can be applied as a strategy to regenerate reliably the tissues and function of damaged periodontium. A prerequisite for this regeneration is the colonization of the defect with the adequate cell populations. In this study, we proposed a bilayered system composed of (1) a platelet lysate (PL)-based construct produced by crosslinking of PL proteins with genipin (gP...

  8. Antithrombin significantly influences platelet adhesion onto immobilized fibrinogen in an in-vitro system simulating low flow

    Directory of Open Access Journals (Sweden)

    Scharf Rüdiger E

    2006-10-01

    Full Text Available Abstract Background Adhesion of platelets onto immobilized fibrinogen is of importance in initiation and development of thrombosis. According to a recent increase in evidence of a multiple biological property of antithrombin, we evaluated the influence of antithrombin on platelet adhesion onto immobilized fibrinogen using an in-vitro flow system. Methods Platelets in anticoagulated whole blood (29 healthy blood donors were labelled with fluorescence dye and perfused through a rectangular flow chamber (shear rates of 13 s-1 to 1500 s-1. Platelet adhesion onto fibrinogen-coated slips was assessed using a fluorescence laser-scan microscope and compared to the plasma antithrombin activity. Additionally the effect of supraphysiological AT supplementation on platelets adhesion rate was evaluated. Results Within a first minute of perfusion, an inverse correlation between platelet adhesion and plasma antithrombin were observed at 13 s-1 and 50 s-1 (r = -0.48 and r = -0.7, p -1, within first minute have been found. An in-vitro supplementation of whole blood with antithrombin increased the antithrombin activity up to 280% and platelet adhesion rate reached about 65% related to the adhesion rate in a non-supplemented blood (1.25 ± 0.17 vs. 1.95 ± 0.4 p = 0.008, respectively. Conclusion It appears that antithrombin in a low flow system suppresses platelet adhesion onto immobilized fibrinogen independently from its antithrombin activity. A supraphysiological substitution of blood with antithrombin significantly reduces platelet adhesion rate. This inhibitory effect might be of clinical relevance.

  9. Propagation capacity of bacterial contaminants in platelet concentrates using a luciferase reporter system.

    Science.gov (United States)

    Bello-López, Juan Manuel; Ibáñez-Cervantes, Gabriela; Fernández-Sánchez, Verónica; Arroyo-Pérez, José Antonio; Rojo-Medina, Julieta

    2015-06-01

    Currently the use of molecular tools and techniques of Genetic Engineering in the study of microbial behavior in blood components has replaced the employment of classical methods of microbiology. This work focuses on the use of a novel lux reporter system for monitoring the contaminating propagation capacity of bacteria present in platelet concentrates under standard storage conditions in the blood bank. A miniTn5 promotor probe carrying the lux operon from Photorhabdus luminiscens (pUTminiTn5luxCDABEKm2) was used to construct four bacterial bioluminescent mutants: Escherichia coli, Salmonella typhi, Proteus mirabilis and Pseudomonas aeruginosa. Luminescent mutants were used for contamination tests with 20 CFU in platelet concentrates bags and were stored under standard storage conditions in the blood bank (100 rpm at 22 °C). The measurements of luminous activity and optical density were used to monitor bacterial proliferation during 7 days (168 h). During the exponential growth phase (log) of bacterial strains, a lineal correlation between luminous activity vs biomass was observed (R(2) = 0.985, 0.976, 0.981) for E. coli::Tn5luxCDABEKm2, P. mirabilis::Tn5luxCDABEKm2 and P. auriginosa::Tn5luxCDABEKm2, respectively. The above indicates that metabolic activity (production of ATP) is directly related to biomass in this phase of microbial growth. While conducting experiments, the inability to propagate S. typhi::Tn5luxCDABEKm2 was detected. We can speculate that platelet concentrates contain specific components that prevent the propagation of S. typhi. The use of luxCDABE system for the quantification of luminous activity is a rapid and sensitive alternative to study the propagation and auto-sterilization of bacterial contaminants in platelet concentrates. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. pH-responsive drug delivery system based on AIE luminogen functionalized layered zirconium phosphate nano-platelets

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dongdong, E-mail: lidongdong@jlu.edu.cn; Zhang, Yuping; Zhou, Bingbing

    2015-05-15

    Aggregation-induced emission (AIE) luminogen, quaternary tetraphenylethene cation (TPEN), was successfully incorporated into layered α-zirconium phosphate (α-ZrP) by using co-precipitation method to form inorganic–organic hybrid materials. The obtained materials show the characteristic hexagonal platelet shape with the interlayer distance did not reveal significant difference compared with pure α-ZrP. In addition, the obtained hybrid materials emit strong blue emission centered at 476 nm in aqueous media due to the electrostatic interactions of TPEN with the anionic framework of α-ZrP, which largely restrict their intramolecular rotation. More importantly, the materials provide a pH dependent release of doxorubicin (DOX), suggesting that AIE luminogen functionalized α-ZrP may be used as an imaging guided and pH-responsive delivery system for targeting therapy. - Graphical abstract: AIE luminogen was successfully incorporated into layered α-zirconium phosphate by a co-precipitation method to form inorganic–organic hybrid materials, showing a pH dependent release of DOX. - Highlights: • AIE luminogen cation was incorporated into layered α-ZrP by co-precipitation method. • The obtained material emits strong blue emission upon UV irradiation. • The material exhibits pH dependent release of DOX. • The AIE functionalized α-ZrP has potential applications in imaging guided therapy.

  11. Effects of LY117018 and the estrogen analogue, 17alpha-ethinylestradiol, on vascular reactivity, platelet aggregation, and lipid metabolism in the insulin-resistant JCR:LA-cp male rat: role of nitric oxide.

    Science.gov (United States)

    Russell, J C; McKendrick, J D; Dubé, P J; Dolphin, P J; Radomski, M W

    2001-01-01

    The JCR:LA-cp rat is obese and insulin resistant and develops a major vasculopathy, with associated ischemic damage to the heart. Male rats were treated with 17alpha-ethinylestradiol (EE), LY117018, and/or the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). LY117018 decreased plasma cholesterol esters, with a 40% reduction in total cholesterol. EE increased triglyceride levels and modestly decreased cholesterol esters. L-NAME increased blood pressure and aortic contractile sensitivity to phenylephrine and inhibited acetylcholine-induced relaxation. LY117018 decreased the force of contraction. The L-NAME-mediated increase in force of contraction and decrease in response to acetylcholine was inhibited by LY117018. L-NAME-induced hypertension was prevented by LY117018. Platelet aggregation was not different between obese and lean rats and was unaffected by L-NAME. LY117018, both in the absence and presence of L-NAME, inhibited platelet aggregation. The effects of LY117018 are apparently mediated through both NO-dependent and -independent mechanisms. The changes induced by EE and LY117018 may reflect the activation of multiple mechanisms, both estrogen receptor-dependent and -independent. The changes induced by LY117018 are significant and may prove to be cardioprotective in the presence of the insulin resistance syndrome.

  12. Competition between aggregation and migration processes of a multi-species system

    Institute of Scientific and Technical Information of China (English)

    Ke Jian-Hong; Zhuang You-Yi; Lin Zhen-Quan; Ye Peng

    2005-01-01

    We propose a solvable multi-species aggregation-migration model, in which irreversible aggregations occur between any two aggregates of the same species and reversible migrations occur between any two different species. The kinetic behaviour of an aggregation-migration system is then studied by means of the mean-field rate equation. The results show that the kinetics of the system depends crucially on the details of reaction events such as initial concentration distributions and ratios of aggregation rates to migration rate. In general, the aggregate mass distribution of each species always obeys a conventional or a generalized scaling law, and for most cases at least one species is scaled according to a conventional form with universal constants. Moreover, there is at least one species that can survive finally.

  13. Diabetic Microvascular Disease and Pulmonary Fibrosis: The Contribution of Platelets and Systemic Inflammation

    Directory of Open Access Journals (Sweden)

    Rekha Jagadapillai

    2016-11-01

    Full Text Available Diabetes is strongly associated with systemic inflammation and oxidative stress, but its effect on pulmonary vascular disease and lung function has often been disregarded. Several studies identified restrictive lung disease and fibrotic changes in diabetic patients and in animal models of diabetes. While microvascular dysfunction is a well-known complication of diabetes, the mechanisms leading to diabetes-induced lung injury have largely been disregarded. We described the potential involvement of diabetes-induced platelet-endothelial interactions in perpetuating vascular inflammation and oxidative injury leading to fibrotic changes in the lung. Changes in nitric oxide synthase (NOS activation and decreased NO bioavailability in the diabetic lung increase platelet activation and vascular injury and may account for platelet hyperreactivity reported in diabetic patients. Additionally, the Janus kinase/signal transducer and activator of transcription (JAK/STAT pathway has been reported to mediate pancreatic islet damage, and is implicated in the onset of diabetes, inflammation and vascular injury. Many growth factors and diabetes-induced agonists act via the JAK/STAT pathway. Other studies reported the contribution of the JAK/STAT pathway to the regulation of the pulmonary fibrotic process but the role of this pathway in the development of diabetic lung fibrosis has not been considered. These observations may open new therapeutic perspectives for modulating multiple pathways to mitigate diabetes onset or its pulmonary consequences.

  14. Bryostatins activate protein kinase C in intact human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.B.; Tallant, E.A.; Pettit, G.R.; Wallace, R.W.

    1986-05-01

    Bryostatins, macrocyclic lactones isolated from a marine bryozoan, have antineoplastic activity in the P388 lymphocytic leukemia system. These compounds also stimulate growth in Swiss 3T3 cells, induce secretion in leukocytes, inhibit phorbol dibutyrate binding to a high affinity receptor, and activate the C-kinase in vitro. In human platelets, phorbol esters induce aggregation and activate protein kinase C, resulting in phosphorylation of a 47K protein and the 20K myosin light chain. The authors now show that bryostatin 7 (B-7) triggers platelet aggregation to the same rate and extent as phorbol 12-myristate 13-acetate (PMA). B-7 also causes the in vivo activation of the C-kinase, resulting in phosphorylation of both the 47K and the 20K proteins; the time courses and dose-responses of these B-7-induced phosphorylations were similar to those found with PMA. In addition, B-7 increases the level of /sup 32/P-incorporation into the platelet polyphosphoinositides, which also occurs in response to PMA. Bryostatin 3 (B-3), which has been shown to be much less potent than B-7 in mimicking other PMA effects, was much less effective than PMA or B-7 in inducing platelet aggregation and in stimulating /sup 32/P-incorporation into both proteins and the phosphoinositides. These results demonstrate that, intact human platelets, bryostatins mimic the phorbol esters tumor promoters and directly activate protein kinase C.

  15. A Numerical Investigation of the Seismic Response of the Aggregate Pier Foundation System

    OpenAIRE

    Girsang, Christian Hariady

    2001-01-01

    The response of an aggregate pier foundation system during seismic loading was investigated. The factors and phenomena governing the performance of the aggregate pier and the improved ground were identified and clarified. The key factors affecting the performance of the aggregate pier include soil density, stiffness modulus, and drainage capacity. The improved ground is influenced by soil stratification, soil properties, pore pressure dissipation, and earthquake time history. Comprehensiv...

  16. An online detection system for aggregate sizes and shapes based on digital image processing

    Science.gov (United States)

    Yang, Jianhong; Chen, Sijia

    2016-07-01

    Traditional aggregate size measuring methods are time-consuming, taxing, and do not deliver online measurements. A new online detection system for determining aggregate size and shape based on a digital camera with a charge-coupled device, and subsequent digital image processing, have been developed to overcome these problems. The system captures images of aggregates while falling and flat lying. Using these data, the particle size and shape distribution can be obtained in real time. Here, we calibrate this method using standard globules. Our experiments show that the maximum particle size distribution error was only 3 wt%, while the maximum particle shape distribution error was only 2 wt% for data derived from falling aggregates, having good dispersion. In contrast, the data for flat-lying aggregates had a maximum particle size distribution error of 12 wt%, and a maximum particle shape distribution error of 10 wt%; their accuracy was clearly lower than for falling aggregates. However, they performed well for single-graded aggregates, and did not require a dispersion device. Our system is low-cost and easy to install. It can successfully achieve online detection of aggregate size and shape with good reliability, and it has great potential for aggregate quality assurance.

  17. Rho GTPases in platelet function.

    Science.gov (United States)

    Aslan, J E; McCarty, O J T

    2013-01-01

    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.

  18. Design and Implementation of Aggregate Functions in the DLV System

    CERN Document Server

    Faber, Wolfgang; Leone, Nicola; Dell'Armi, Tina; Ielpa, Giuseppe

    2008-01-01

    Disjunctive Logic Programming (DLP) is a very expressive formalism: it allows for expressing every property of finite structures that is decidable in the complexity class SigmaP2 (= NP^NP). Despite this high expressiveness, there are some simple properties, often arising in real-world applications, which cannot be encoded in a simple and natural manner. Especially properties that require the use of arithmetic operators (like sum, times, or count) on a set or multiset of elements, which satisfy some conditions, cannot be naturally expressed in classic DLP. To overcome this deficiency, we extend DLP by aggregate functions in a conservative way. In particular, we avoid the introduction of constructs with disputed semantics, by requiring aggregates to be stratified. We formally define the semantics of the extended language (called DLP^A), and illustrate how it can be profitably used for representing knowledge. Furthermore, we analyze the computational complexity of DLP^A, showing that the addition of aggregates d...

  19. Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II)

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Gustafsson, Finn; Mortensen, Svend A

    2009-01-01

    OBJECTIVES: This study investigated the influence of the mechanical blood pump HeartMate II (HMII) (Thoratec Corporation, Pleasanton, California) on blood coagulation and platelet function. BACKGROUND: HMII is an implantable left ventricular assist device used for the treatment of heart failure...

  20. Structural Organization in the System of Magnetized Aggregates in Elliptically Polarized Rotating Magnetic Field

    Directory of Open Access Journals (Sweden)

    Yu.I. Dikansky

    2014-07-01

    Full Text Available Observed data supporting the possibility of magnetic ordering in magnetic colloids are reported. A possibility of aggregate spatial ordering in a system of magnetized aggregates was found under the influence of rotating and crossed constant and alternating magnetic fields.

  1. The Effect of Ticagrelor on Platelet Aggregation Ratio in Patients with Clopidogrel Resistance%替格瑞洛在治疗氯吡格雷抵抗患者时血小板聚集率分析

    Institute of Scientific and Technical Information of China (English)

    李江; 刘文娴; 赵一楠; 任燕龙

    2014-01-01

    Objective To research the variance of the platelet aggregation ratio after using ticagrelor instead of clopi-dogrel in patients with clopidogrel resistance. Methods Adenosine diphosphate( ADP)induced platelet aggregation ratio test was run to identify patients with clopidogrel resistance in 512 patients undergoing the treatment of percutaneous coronary interven-tion( PCI)and clopidogrel 75 mg/d. 88 patients with clopidogrel resistance were given randomly clopidogrel 75 mg/d or ticagrelor (90 mg twice a day)for 7 days and took the test of the platelet aggregation ratio after the treatment. Results Aftertreatment for ti-cagrelor group compared with clopidogrel platelet aggregation rate low〔(43. 3 ± 8. 2)% vs. (56. 9 ± 5. 3)%〕,the difference was statistically significant ( P ﹤0. 05 );for the ticagrelor group, platelet aggregation rate decrease than clopidogrel group〔(16. 4 ±9. 8)% vs. (1. 1 ± 4. 1)%〕,the difference is statistically significant(P﹤0. 05);for the the ticagrelor group, platelet aggregation rate compliance rate than clopidogrel group was higher(84. 4% vs. 4. 7%),the difference was statistically significant(P﹤0. 05);for the ticagrelor group and clopidogrel group in the course of the experiment showed no major bleed-ing. Conclusion Ticagrelor,comparing the regular-dose treatment of clopidogrel,can decrease the platelet aggregation ratio in patients with clopidogrel resistance.%目的:探讨在治疗氯吡格雷抵抗患者时,将氯吡格雷更换为替格瑞洛后血小板聚集率的变化情况。方法选择正在应用氯吡格雷75 mg/d治疗的经皮冠状动脉介入治疗( PCI)术后患者512例,用比浊法测定血小板聚集率,根据血小板聚集率筛选出氯吡格雷抵抗患者88例。然后将这88例患者1:1随机分为氯吡格雷组及替格瑞洛组,氯吡格雷组继续服用氯吡格雷(75 mg/d),替格瑞洛组将氯吡格雷(75 mg/d)更换为替格瑞洛(90 mg,2次/d)。随访7d

  2. Assessment of roles for the Rho-specific guanine nucleotide dissociation inhibitor (RhoGDI) Ly-GDI in platelet function: a spatial systems approach.

    Science.gov (United States)

    Ngo, Anh T P; Thierheimer, Marisa L D; Babur, Özgün; Rocheleau, Anne D; Huang, Tao; Pang, Jiaqing; Rigg, Rachel A; Mitrugno, Annachiara; Theodorescu, Dan; Burchard, Julja; Nan, Xiaolin; Demir, Emek; McCarty, Owen J T; Aslan, Joseph E

    2017-02-01

    Upon activation at sites of vascular injury, platelets undergo morphological alterations essential to hemostasis via cytoskeletal reorganizations driven by the Rho GTPases Rac1, Cdc42 and RhoA. Here we investigate roles for Rho-specific guanine nucleotide dissociation inhibitor proteins (RhoGDIs) in platelet function. We find that platelets express two RhoGDI family members, RhoGDI and Ly-GDI. While RhoGDI localizes throughout platelets in a granule-like manner, Ly-GDI shows an asymmetric, polarized localization that largely overlaps with Rac1 and Cdc42 as well as microtubules and protein kinase C (PKC) in platelets adherent to fibrinogen. Antibody interference and platelet spreading experiments suggest a specific role for Ly-GDI in platelet function. Intracellular signaling studies based on interactome and pathways analyses also support a regulatory role for Ly-GDI, which is phosphorylated at PKC substrate motifs in a PKC-dependent manner in response to the platelet collagen receptor glycoprotein (GP)VI-specific agonist collagen-related peptide. Additionally, PKC inhibition diffuses the polarized organization of Ly-GDI in spread platelets relative to its colocalization with Rac1 and Cdc42. Together our results suggest a role for Ly-GDI in the localized regulation of Rho GTPases in platelets and hypothesize a link between the PKC and Rho GTPase signaling systems in platelet function.

  3. Increase in phosphotidylinositide-3 kinase activity by nitrotyrosylation of lysates of platelets from patients with systemic sclerosis.

    Science.gov (United States)

    Chiang, Thomas M; Postlethwaite, Arnold E

    2006-01-01

    We have observed that the platelet non-integrin collagen receptor (65 kDa) and another protein (M(r) 185 kDa) are altered in the posttranslational modification by nitrotyrosylation in platelets from patients with systemic sclerosis (SSc). We reported the identification of nitrotyrosylated 65-kDa proteins in a previous study. In the present investigation, using Western blots, one- and two-dimensional gel electrophoreses and matrix assisted ionization/desorption-time of flight (MALDI-TOF) we have identified the 185-kDa protein as phosphoinositide kinase C2beta (PI 3-K). There is a positive correlation between the nitrotyrosylation of PI 3-K and activity of the enzyme, i.e., the nitrotyrosylation of PI 3-K increases its enzymatic activity. In addition, the activity of PI 3-K increases in nitrotyrosylated platelet lystaes from patients with SSc compared to normal volunteer controls, suggesting that this is an alteration in the posttranslational modification of PI 3-K in platelets from patients with SSc. The increased nitrotyrosylation of PI 3-K may contribute to the impairment of platelet function in patients with SSc by increasing platelet reactivity to matrix components within the vascular walls of patients with this disease.

  4. Platelet-derived growth factor receptor/platelet-derived growth factor (PDGFR/PDGF) system is a prognostic and treatment response biomarker with multifarious therapeutic targets in cancers.

    Science.gov (United States)

    Appiah-Kubi, Kwaku; Wang, Ying; Qian, Hai; Wu, Min; Yao, Xiaoyuan; Wu, Yan; Chen, Yongchang

    2016-08-01

    Progress in cancer biology has led to an increasing discovery of oncogenic alterations of the platelet-derived growth factor receptors (PDGFRs) in cancers. In addition, their overexpression in numerous cancers invariably makes PDGFRs and platelet-derived growth factors (PDGFs) prognostic and treatment markers in some cancers. The oncologic alterations of the PDGFR/PDGF system affect the extracellular, transmembrane and tyrosine kinase domains as well as the juxtamembrane segment of the receptor. The receptor is also involved in fusions with intracellular proteins and receptor tyrosine kinase. These discoveries undoubtedly make the system an attractive oncologic therapeutic target. This review covers elementary biology of PDGFR/PDGF system and its role as a prognostic and treatment marker in cancers. In addition, the multifarious therapeutic targets of PDGFR/PDGF system are discussed. Great potential exists in the role of PDGFR/PDGF system as a prognostic and treatment marker and for further exploration of its multifarious therapeutic targets in safe and efficacious management of cancer treatments.

  5. 岩乌头根部的生物碱类成分及其抗PAF活性%Diterpenoid Alkaloids from roots of Aconitum recemulosum and their inhibitory effects on PAF-induced platelet aggregation

    Institute of Scientific and Technical Information of China (English)

    葛永辉; 穆淑珍; 张建新; 汪冶; 孙黔云; 郝小江

    2009-01-01

    Objective:To study diterpenoid alkaloids from the roots of Aconitum recemulosum,and their inhibitory effects on PAF-induced platelet aggregation.Method:The root of A.recemulosum was extracted with 95% EtOH.The total alkaloids extracted were isolated and purified by several kinds of column chromatography over silica gel,RP-18,and Sephadex LH-20,and identified based on spectral analysis.And the inhibitory effects of isolated compounds on PAF-induced platelet aggregation were detected.Result:Five alkaloids were isolated and identified as sachaconitine(1),14-acetylsachaconitine(2),hemsleyanine C(3),circinasine A(4),and talatisamine(5).The results showed compounds 1 and 2 have moderate inhibition effect on PAF.Conclusion:Compounds 1-5 were firstly isolated from this plant.Furthermore,compounds 1 and 2 possessed moderate inhibitory effects on PAF-induced platelet aggregation.%目的:研究岩乌头根部的二萜生物碱类成分及其抗PAF活性.方法:95%乙醇提取,所得浸膏采用经典的酸-碱处理方法,得到总碱,总碱经硅胶,RP-18,sephadex LH-20等多种材料柱色谱分离,得到生物碱单体,再通过波谱解析鉴定其化学结构;并对分离鉴定的生物碱进行抗PAF活性的检测.结果:分离鉴定了5个二萜类生物碱,分别为sachaconitine(1),14-acetylsachaconitine(2),hemsleyanine C(3),circinasine A(4),talatisamine(5);化合物1和2显示了一定的抗PAF活性.结论:所有化合物均为首次从该植物中分得,化合物1和2对PAF诱导的血小板聚集具有一定的抑制作用.

  6. Inherited platelet disorders and oral health.

    Science.gov (United States)

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

    2013-02-01

    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.

  7. Effect of tillage system on distribution of aggregates and organic carbon in a hydragric anthrosol

    Institute of Scientific and Technical Information of China (English)

    GAO Ming; LUO You-Jin; WANG Zi-Fang; TANG Xiao-Hong; WEI Chao-Fu

    2008-01-01

    The effect of different tillage systems on the size distribution of aggregates and organic carbon distribution and storage in different size aggregates in a Hydragric Anthrosol were studied in a long-term experiment in Chongqing,China.The experiment included three tillage treatments:conventional tillage with rotation of rice and winter fallow (CT-r) system,no-till and ridge culture with rotation of rice and rape (RT-rr) system,and conventional tillage with rotation of rice and rape (CT-rr) system.The results showed that the aggregates 0.02-0.25 mm in diameter accounted for the largest portion in each soil layer under all treatments.Compared with the CT-r system,in the 0-10 cm layer,the amount of aggregates>0.02 mm was larger under the RT-rr system,but smaller under the CT-rr system.In the 0-20 cm layer,the organic carbon content of all fractions of aggregates was the highest under the RT-rr system and lowest under the CT-rr system.The total organic carbon content showed a positive linear relationship with the amount of aggregates with diameter ranging from 0.25 to 2 ram.The storage of organic carbon in all fractions of aggregates under the RT-rr system was higher than that under the CT-r system in the 0-20 cm layer,but in the 0-60 cm soil layer,there was no distinct difference.Under the CT-rr system,the storage of organic carbon in all fractions of aggregates was lower than that under the CT-r system;most of the newly lost organic carbon was from the aggregates 0.002-0.02 and 0.02-0.25 mm in diameter.

  8. In vitro function of random donor platelets stored for 7 days in composol platelet additive solution

    Directory of Open Access Journals (Sweden)

    Gupta Ashish

    2011-01-01

    Full Text Available Background and Aim: Platelets are routinely isolated from whole blood and stored in plasma for 5 days. This 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, C S M Medical University, Lucknow. Random donor platelets were prepared by the 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 while 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 the platelet viability and aggregation were the 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.

  9. PREGNANCY WITH PLATELET FUNCTION DISORDER

    Directory of Open Access Journals (Sweden)

    Sheila K

    2014-01-01

    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

  10. Effect of polytetrafluoroethylene artificial blood vessels on platelet aggregation and its cytocompatibility%聚四氟乙烯人工血管对血小板聚集的影响及细胞相容性

    Institute of Scientific and Technical Information of China (English)

    姜正明; 陈魁; 胡彩娜

    2016-01-01

    背景:聚四氟乙烯人工血管是临床常用的医用材料,但其具体的基础研究内容尚未完善。目的:观察聚四氟乙烯人工血管对血小板聚集的作用及细胞相容性。方法:①对血小板聚集的作用:检测聚四氟乙烯人工血管的凝血时间、复钙时间。将生理盐水、蒸馏水及聚四氟乙烯人工血管分别加入兔红细胞悬液中,计算溶血率;②细胞生物相容性:将SD大鼠原代心肌细胞分别接种于普通玻璃爬片与聚四氟乙烯人工血管片上,3 d后,检测细胞乳酸脱氢酶释放;5 d后,检测细胞增殖。结果与结论:①聚四氟乙烯人工血管对兔血的动态凝血时间、复钙时间没有影响;聚四氟乙烯人工血管的溶血率为2.3%;②与接种于普通玻璃爬片上的心肌细胞相比,接种于聚四氟乙烯人工血管片上的心肌细胞增殖及乳酸脱氢酶释放无明显变化;③结果表明,聚四氟乙烯人工血管血小板聚集无影响,具有良好的血液相容性与细胞相容性。%BACKGROUND:Polytetrafluoroethylene artificial blood vessels have been extensively used in clinic. However, there is stil a lack of basic study on it. OBJECTIVE:To observe the effect of polytetrafluoroethylene artificial blood vessels on platelet aggregation and its cytocompatibility. METHODS:Effect on platelet aggregation:Dynamic platelet clotting time and plasma recalcification time were detected. Normal saline, distil ed water and polytetrafluoroethylene artificial blood vessels were added into the rabbit red cel suspensions, respectively, to count the hemolysis ratio. Cytocompatibility:Primary myocardial cel s from Sprague-Dawley rats were respectively seeded onto the common round coverslip and polytetrafluoroethylene artificial blood vessels, and the lactate deshydrogenase release and cel proliferation were detected at 3 and 5 days, respectively. RESULTS AND CONCLUSION:Polytetrafluoroethylene artificial

  11. Overview of platelet physiology and laboratory evaluation of platelet function.

    Science.gov (United States)

    Rodgers, G M

    1999-06-01

    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

  12. 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

    2016-01-01

    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.

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

    Science.gov (United States)

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

    2016-02-01

    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. Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets: The inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAAD-Tica) study, a randomised controlled trial.

    Science.gov (United States)

    Venetsanos, Dimitrios; Sederholm Lawesson, Sofia; Swahn, Eva; Alfredsson, Joakim

    2017-01-01

    To provide pharmacodynamic data of crushed and chewed ticagrelor tablets, in comparison with standard integral tablets. Ninety nine patients with stable angina were randomly assigned, in a 3:1:1 fashion, to one of the following 180mg ticagrelor loading dose (LD) formulations: A) Integral B) Crushed or C) Chewed tablets. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60min after LD. High residual platelet reactivity (HRPR) was defined as >208 P2Y12 reaction units (PRU). There was no significant difference in PRU values at baseline. PRU 20min after LD were 237 (182-295), 112 (53-238) and 84 (29-129) and 60min after LD, 56 (15-150), 51 (18-85) and 9 (7-34) in integral, crushed and chewed ticagrelor LD, respectively (pintegral tablets at 20 and 60min. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20min whereas no difference was observed at 60min. At 20min, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (pintegral tablets. We also show that administration of chewed tablets is feasible and provides faster inhibition than either crushed or integral tablets. European Clinical Trial Database (EudraCT number 2014-002227-96). Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Platelet Count

    Science.gov (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 ...

  16. Platelet inhibition by nitrite is dependent on erythrocytes and deoxygenation.

    Directory of Open Access Journals (Sweden)

    Sirada Srihirun

    Full Text Available BACKGROUND: Nitrite is a nitric oxide (NO metabolite in tissues and blood, which can be converted to NO under hypoxia to facilitate tissue perfusion. Although nitrite is known to cause vasodilation following its reduction to NO, the effect of nitrite on platelet activity remains unclear. In this study, the effect of nitrite and nitrite+erythrocytes, with and without deoxygenation, on platelet activity was investigated. METHODOLOGY/FINDING: Platelet aggregation was studied in platelet-rich plasma (PRP and PRP+erythrocytes by turbidimetric and impedance aggregometry, respectively. In PRP, DEANONOate inhibited platelet aggregation induced by ADP while nitrite had no effect on platelets. In PRP+erythrocytes, the inhibitory effect of DEANONOate on platelets decreased whereas nitrite at physiologic concentration (0.1 µM inhibited platelet aggregation and ATP release. The effect of nitrite+erythrocytes on platelets was abrogated by C-PTIO (a membrane-impermeable NO scavenger, suggesting an NO-mediated action. Furthermore, deoxygenation enhanced the effect of nitrite as observed from a decrease of P-selectin expression and increase of the cGMP levels in platelets. The ADP-induced platelet aggregation in whole blood showed inverse correlations with the nitrite levels in whole blood and erythrocytes. CONCLUSION: Nitrite alone at physiological levels has no effect on platelets in plasma. Nitrite in the presence of erythrocytes inhibits platelets through its reduction to NO, which is promoted by deoxygenation. Nitrite may have role in modulating platelet activity in the circulation, especially during hypoxia.

  17. X-ray computed tomography and aggregate image system (AIMS for studying hot mix asphalt and aggregates

    Directory of Open Access Journals (Sweden)

    Allex E. Álvarez Lugo

    2010-04-01

    Full Text Available Achieving reliable pavement design, durable roadway structures and effective maintenance and rehabilitation plans requires the suitable characterisation of the materials used in pavement construction. This paper describes two non-destructive techniques based on image acquisition and analysis and their successful application in pavement engi-neering: X-ray computed tomography (X-ray CT and aggregate imaging system (AIMS. The former has been used for characterising the internal structure of asphalt mixes to analyse and model their performance; it has been particu-larly used for studying the content, size, distribution and connectivity of air-voids and these variables’ relationship with moisture damage susceptibility, capillarity and permeability within the mixes. AIMS was intended for characterri-sing aggregates’ morphological properties (i.e., form, angularity and texture. This technique provides important ad-vantages regarding the standard methods used for obtaining the same aggregate properties: it is objective, reliable, reproducible and can be carried out quickly. This paper was aimed at describing these two techniques’ theoretical backgrounds, mention some recent applications and provide insight into how existing characterisation of materials used in pavement construction can be improved.

  18. Platelet-Derived Growth Factor as a Therapeutic Target for Systemic Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Hideto Kameda

    2007-01-01

    Full Text Available Some systemic rheumatic diseases and disorders, especially fibrotic and vascular disorders, are often refractory to corticosteroid therapy. Recently, ever accumulating evidence suggests that platelet-derived growth factor (PDGF is involved in those refractory diseases. Imatinib mesylate inhibits the activation of PDGF receptor as well as c-Abl, Bcr-Abl and c-Kit tyrosine kinases. It has therefore been widely used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Imatinib effectively suppresses the activation and proliferation of fibroblasts, mesangial cells and smooth muscle cells both in vitro and in vivo. Additionally, it has recently been reported that some patients with rheumatoid arthritis or idiopathic pulmonary arterial hypertension demonstrated a good clinical response to imatinib therapy. Imatinib may therefore overcome the limitations of current therapeutic strategy with corticosteroids and immunosuppressive agents for refractory diseases, such as systemic sclerosis and interstitial lung diseases, without clinical intolerability.

  19. Caffeic acid treatment alters the extracellular adenine nucleotide hydrolysis in platelets and lymphocytes of adult rats.

    Science.gov (United States)

    Anwar, Javed; Spanevello, Roselia Maria; Pimentel, Victor Camera; Gutierres, Jessié; Thomé, Gustavo; Cardoso, Andreia; Zanini, Daniela; Martins, Caroline; Palma, Heloisa Einloft; Bagatini, Margarete Dulce; Baldissarelli, Jucimara; Schmatz, Roberta; Leal, Cláudio Alberto Martins; da Costa, Pauline; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

    2013-06-01

    This study evaluated the effects of caffeic acid on ectonucleotidase activities such as NTPDase (nucleoside triphosphate diphosphohydrolase), Ecto-NPP (nucleotide pyrophosphatase/phosphodiesterase), 5'-nucleotidase and adenosine deaminase (ADA) in platelets and lymphocytes of rats, as well as in the profile of platelet aggregation. Animals were divided into five groups: I (control); II (oil); III (caffeic acid 10 mg/kg); IV (caffeic acid 50 mg/kg); and V (caffeic acid 100 mg/kg). Animals were treated with caffeic acid diluted in oil for 30 days. In platelets, caffeic acid decreased the ATP hydrolysis and increased ADP hydrolysis in groups III, IV and V when compared to control (P<0.05). The 5'-nucleotidase activity was decreased, while E-NPP and ADA activities were increased in platelets of rats of groups III, IV and V (P<0.05). Caffeic acid reduced significantly the platelet aggregation in the animals of groups III, IV and V in relation to group I (P<0.05). In lymphocytes, the NTPDase and ADA activities were increased in all groups treated with caffeic acid when compared to control (P<0.05). These findings demonstrated that the enzymes were altered in tissues by caffeic acid and this compound decreased the platelet aggregation suggesting that caffeic acid should be considered a potentially therapeutic agent in disorders related to the purinergic system.

  20. Discerning Aggregation in Homogeneous Ensembles: A General Description of Photon Counting Spectroscopy in Diffusing Systems

    CERN Document Server

    Ren, H; Altan-Bonnet, G; Libchaber, A; Ren, Hai-cang; Goddard, Noel L.; Altan-Bonnet, Gregoire; Libchaber, Albert

    2004-01-01

    In order to discern aggregation in solutions, we present a quantum mechanical analog of the photon statistics from fluorescent molecules diffusing through a focused beam. A generating functional is developed to fully describe the experimental physical system as well as the statistics. Histograms of the measured time delay between photon counts are fit by an analytical solution describing the static as well as diffusing regimes. To determine empirical fitting parameters, fluorescence correlation spectroscopy is used in parallel to the photon counting. For expedient analysis, we find that the distribution's deviation from a single Poisson shows a difference between two single fluor moments or a double fluor aggregate of the same total intensities. Initial studies were performed on fixed-state aggregates limited to dimerization. However preliminary results on reactive species suggest that the method can be used to characterize any aggregating system.

  1. The formalism of fractal aggregation phenomena of colloidal drug delivery systems.

    Science.gov (United States)

    Pippa, Natassa; Demetzos, Costas; Danezis, Emmanuel

    2012-03-01

    Classical Newtonian Physics and Euclidean Geometry are currently used to describe biological phenomena and the processes of drug formulation, which are characterized by homogeneity and linearity. On the other hand, at the mesoscopic level, the principles and the laws of physics are quite different from the Classical Newtonian Physics and Euclidean approach especially at nanoscale dimension. The investigation of the aggregation process of liposomes is of paramount importance due to their applications in pharmaceutical nanotechnology as drug delivery systems and as membrane models, in biosciences. The physical stability and the aggregation process of colloidal systems as well as the surface phenomena are described using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The elucidation of the dimensionality of liposome aggregates obeys the fractal approach because the aggregation phenomena are irreversible. This approach can be correlated with the extended DLVO theory, which includes the hydration energy, too.

  2. 钩藤碱对家兔血小板聚集及胞浆游离钙离子浓度的影响%Effect of rhynchophylline on platelet aggregation and cytoplasmic free calcium level in rabbits

    Institute of Scientific and Technical Information of China (English)

    谢笑龙; 龚其海; 陆远富; 邓江; 聂晶; 陈文明; 石京山

    2011-01-01

    OBJECTIVE To investigate the effect of rhynchophylline (Rhy) on the rabbit cytoplasmic free calcium level and platelet aggregation, and the possible mechanism. METHODS Blood samples from 56 male rabbits were randomly divided into control group ( normal saline), aspirin(Asp) 0.85, 1.69 and 2.78 mmol ·L-1 groups, and Rhy 0.33, 0.65 and 1.30 mmol·L-1 groups. Platelet aggregation and cytoplasmic free calcium level were determined by Born method and double beam fluorescence spectrophotometric method, respectively. RESULTS Compared with the platelet aggregation rate (59.6 ±0.6)% in control group induced by ADP 15 μmol·L-1, the platelet aggregation rates in Rhy 0.33, 0.65 and 1.30 mmol· L- 1 groups were decreased to ( 35.4 ±7.7 ) %, ( 18.2 ± 4.8 ) % and (6.9 ± 0.9 ) %, respectively ( P < 0.05 ). Compared with control group ( 80.8 ± 1.5 ) %, the maximum platelet aggregation rate induced by thrombin 3 kU· L- 1 in Rhy 0.65 and 1.30 mmol·L - 1 was (42.8 ± 3.9 ) % and ( 18.9 ± 5.5 ) % ( P < 0.05 ), respectively. In the presence of extracellular Ca2+ , a comparison of the cytoplasmic free calcium level (528 ± 25 )nmol·L -1 in control group and Rhy group was performed. Rhy 0.33, 0.65 and 1.30 mmol·L -1 depressed obviously the cytoplasmic free calcium level to 418 ±27,303 ±7 and (257 ±25 )nmol·L-1,respectively. During the inducement of ADP and thrombin, the cytoplasmic free calcium level in control group was 751 ± 29 and ( 982 ± 50 ) nmol· L- 1. After Rhy 0.65 and 1.30 mmol· L - 1 were administered, the cytoplasmic free calcium level induced by ADP decreased to 620 ± 37 and (528 ±17)nmol·L-1, respectively (P < 0. 05), the cytoplasmic free calcium level induced by thrombin decreased to 777 ± 29 and ( 658 ± 23 ) nmol· L-1, respectively ( P < 0.05 ).In the absence of extracellular Ca2+ , Rhy had no significant influence on cytoplasmic free calcium level of rabbit platelet. CONCLUSION Rhy markedly inhibits rabbit platelet

  3. Doxorubicin-loaded platelets as a smart drug delivery system: An improved therapy for lymphoma

    Science.gov (United States)

    Xu, Peipei; Zuo, Huaqin; Chen, Bing; Wang, Ruju; Ahmed, Arsalan; Hu, Yong; Ouyang, Jian

    2017-01-01

    Chemotherapy is majorly used for the treatment of many cancers, including lymphoma. However, cytotoxic drugs, utilized in chemotherapy, can induce various side effects on normal tissues because of their non-specific distribution in the body. Natural platelets are used as drug carriers because of their biocompatibility and specific targeting to vascular disorders, such as cancer, inflammation, and thrombosis. In this work, doxorubicin (DOX) was loaded in natural platelets for treatment of lymphoma. Results showed that DOX was loaded into platelets with high drug loading and encapsulation efficiency. DOX did not significantly induce morphological and functional changes in platelets. DOX-platelet facilitated intracellular drug accumulation through “tumor cell-induced platelet aggregation” and released DOX into the medium in a pH-controlled manner. This phenomenon reduced the adverse effects and enhanced the therapeutic efficacy. The growth inhibition of lymphoma Raji cells was enhanced, and the cardiotoxicity of DOX was reduced when DOX was loaded in platelets. DOX-platelet improved the anti-tumor activity of DOX by regulating the expression of apoptosis-related genes. Thus, platelets can serve as potential drug carriers to deliver DOX for clinical treatment of lymphoma. PMID:28198453

  4. 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.

  5. The Toxicity of a Chemically Synthesized Peptide Derived from Non-Integrin Platelet Collagen Receptors

    Directory of Open Access Journals (Sweden)

    Thomas M. Chiang

    2008-01-01

    Full Text Available A chemically synthesized peptide derived from platelet non-integrin collagen receptor has been shown to be an effective agent for inhibiting collagen-induced platelet aggregation and adhesion of washed radiolabeled platelets onto natural matrices and collagen coated microtiter plates. In order to be a therapeutic agent, we have used a cell culturing system and an animal model to test its cytotoxicities. In cell culture experiments, the peptide is not toxic to MEG-01, a megakaryoblastic cell line. Prior to performing experiments in rats, the existence of both platelet type I and type III collagen receptors and its functional roles in rat platelets had to be established. In this investigation, we report that rat platelets contain both receptors and the cHyB peptide inhibits both type I and type III collagen-induced rat platelet aggregation. In addition, analysis of the rat sera collected at various time intervals following an injection of cHyB into the rat-tail vein, did not show an increase in the activity of key enzymes which indicate tissue and/or organ damage. These results suggest that the cHyB peptide is safe and its development into a potential therapeutic agent for inhibiting thrombi formation is possible.

  6. The Toxicity of a Chemically Synthesized Peptide Derived from Non-Integrin Platelet Collagen Receptors

    Directory of Open Access Journals (Sweden)

    Thomas M. Chiang

    2008-08-01

    Full Text Available A chemically synthesized peptide derived from platelet non-integrin collagen receptor has been shown to be an effective agent for inhibiting collagen-induced platelet aggregation and adhesion of washed radiolabeled platelets onto natural matrices and collagen coated microtiter plates. In order to be a therapeutic agent, we have used a cell culturing system and an animal model to test its cytotoxicities. In cell culture experiments, the peptide is not toxic to MEG-01, a megakaryoblastic cell line. Prior to performing experiments in rats, the existence of both platelet type I and type III collagen receptors and its functional roles in rat platelets had to be established. In this investigation, we report that rat platelets contain both receptors and the cHyB peptide inhibits both type I and type III collagen-induced rat platelet aggregation. In addition, analysis of the rat sera collected at various time intervals following an injection of cHyB into the rat-tail vein, did not show an increase in the activity of key enzymes which indicate tissue and/or organ damage. These results suggest that the cHyB peptide is safe and its development into a potential therapeutic agent for inhibiting thrombi formation is possible.

  7. Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

    Science.gov (United States)

    Reed, G. L.; Matsueda, G. R.; Haber, E.

    1992-01-01

    Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

  8. Aggregated Modelling for Wind Farms for Power System Transient Stability Studies

    DEFF Research Database (Denmark)

    Liu, Hongzhi; Chen, Zhe

    2012-01-01

    Wind energy is consistently attracting great research effort and actively developed in many countries. As a result, the penetration level of wind power in the power grid is increasing as well as the size of wind farms. A large-scale wind farm may consist of hundreds of wind turbines and its total...... on a wind farm with permanent magnet synchronous generator (PMSG) wind turbines. Simulation results of the aggregated models and the detailed model are compared and analyzed respectively to prove the effectiveness of the aggregating techniques....... installed capacity could be at a level of 1000MW or even more. Consequently, the large-scale wind farm could seriously impact the operation and control of the grid. To represent a large-scale wind farm, aggregated modelling takes advantage of fast computation and simplified implementation compared...... to detailed modelling that models every wind turbines individually and the interconnections among them. In this paper, three aggregated modelling techniques, namely, multi-machine equivalent aggregation, full aggregation and semi-aggregation are presented for power system transient stability studies based...

  9. Matrix metalloproteinase-2 enhances platelet deposition on collagen under flow conditions.

    Science.gov (United States)

    Guglielmini, Giuseppe; Appolloni, Viviana; Momi, Stefania; De Groot, Philip G; Battiston, Monica; De Marco, Luigi; Falcinelli, Emanuela; Gresele, Paolo

    2016-01-01

    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. Differential Expression Analysis by RNA-Seq Reveals Perturbations in the Platelet mRNA Transcriptome Triggered by Pathogen Reduction Systems.

    Directory of Open Access Journals (Sweden)

    Abdimajid Osman

    Full Text Available Platelet concentrates (PCs are prepared at blood banks for transfusion to patients in certain clinical conditions associated with a low platelet count. To prevent transfusion-transmitted infections via PCs, different pathogen reduction (PR systems have been developed that inactivate the nucleic acids of contaminating pathogens by chemical cross-linking, a mechanism that may also affect platelets' nucleic acids. We previously reported that treatment of stored platelets with the PR system Intercept significantly reduced the level of half of the microRNAs that were monitored, induced platelet activation and compromised the platelet response to physiological agonists. Using genome-wide differential expression (DE RNA sequencing (RNA-Seq, we now report that Intercept markedly perturbs the mRNA transcriptome of human platelets and alters the expression level of >800 mRNAs (P<0.05 compared to other PR systems and control platelets. Of these, 400 genes were deregulated with DE corresponding to fold changes (FC ≥ 2. At the p-value < 0.001, as many as 147 genes were deregulated by ≥ 2-fold in Intercept-treated platelets, compared to none in the other groups. Finally, integrated analysis combining expression data for microRNA (miRNA and mRNA, and involving prediction of miRNA-mRNA interactions, disclosed several positive and inverse correlations between miRNAs and mRNAs in stored platelets. In conclusion, this study demonstrates that Intercept markedly deregulates the platelet mRNA transcriptome, concomitant with reduced levels of mRNA-regulatory miRNAs. These findings should enlighten authorities worldwide when considering the implementation of PR systems, that target nucleic acids and are not specific to pathogens, for the management of blood products.

  11. The significance of platelet-associated immunoglobulin G in non-thrombocytopenic patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Sørensen, P G; Mickley, H; Fristed, P

    1985-01-01

    The possible pathogenetic significance of platelet-associated immunoglobulin G in systemic lupus erythematosus (SLE) has been studied, using a semiquantitative immunofluorescence technique. The study included 22 patients suffering from SLE during the period 1973-81. Thirteen patients had various...

  12. Development and Application of a Structural Health Monitoring System Based on Wireless Smart Aggregates.

    Science.gov (United States)

    Yan, Shi; Ma, Haoyan; Li, Peng; Song, Gangbing; Wu, Jianxin

    2017-07-17

    Structural health monitoring (SHM) systems can improve the safety and reliability of structures, reduce maintenance costs, and extend service life. Research on concrete SHMs using piezoelectric-based smart aggregates have reached great achievements. However, the newly developed techniques have not been widely applied in practical engineering, largely due to the wiring problems associated with large-scale structural health monitoring. The cumbersome wiring requires much material and labor work, and more importantly, the associated maintenance work is also very heavy. Targeting a practical large scale concrete crack detection (CCD) application, a smart aggregates-based wireless sensor network system is proposed for the CCD application. The developed CCD system uses Zigbee 802.15.4 protocols, and is able to perform dynamic stress monitoring, structural impact capturing, and internal crack detection. The system has been experimentally validated, and the experimental results demonstrated the effectiveness of the proposed system. This work provides important support for practical CCD applications using wireless smart aggregates.

  13. Patients with previous definite stent thrombosis have a larger fraction of immature platelets and a reduced antiplatelet effect of aspirin

    DEFF Research Database (Denmark)

    Würtz, Morten; Grove, Erik; Wulff, Lise Nielsen;

    turnover. Key Words: aspirin; immature platelets; platelet aggregation; platelet function tests; stent thrombosis Abbreviations: ARU, aspirin reaction units; AU, aggregation units; BMS, bare-metal stent(s); DES, drug-eluting stent(s); IPF, immature platelet fraction; MEA, multiple electrode aggregometry...

  14. Erythrocyte: A systems model of the control of aggregation and deformability.

    Science.gov (United States)

    Bazanovas, Antonina N; Evstifeev, Aleksandr I; Khaiboullina, Svetlana F; Sadreev, Ildar I; Skorinkin, Andrey I; Kotov, Nikolay V

    2015-05-01

    Human erythrocytes are highly specialized enucleate cells that are involved in providing efficient gas transport. Erythrocytes have been extensively studied both experimentally and by mathematical modeling in recent years. However, understanding of how aggregation and deformability are regulated is limited. These properties of the erythrocyte are essential for the physiological functioning of the cell. In this work, we propose a novel mathematical model of the molecular system that controls the aggregation and deformability of the erythrocyte. This model is based on the experimental results of previously published studies. Our model suggests fundamentally new mechanisms that regulate aggregation and deformability in a latch-like manner. The results of this work could be used as a general explanation of how the erythrocytes regulate their aggregation and deformability, and are essential in understanding erythrocyte disorders and aging.

  15. Activation of circulating platelets and platelet response to activating agents in children with cyanotic congenital heart disease: their relevance to palliative systemic-pulmonary shunt.

    Science.gov (United States)

    Kierzkowska, B; Stańczyk, J; Wiectawska, B; Rózalski, M; Boncler, M; Chrul, S; Watala, C

    2001-06-01

    Abnormal platelet function has been hypothesised to play a role in the haemostatic abnormalities in cyanotic congenital heart disease (CCHD) patients. Using whole blood flow cytometry we found that platelets from cyanotic patients were hyperreactive and we related such hyperreactivity directly to young age, unoperated state, high haematocrit, reduced saturation with oxygen and low platelet count. Circulating platelets from CCHD children showed significantly enhanced P-selectin expression (Pplatelet 'priming' largely concerned CCHD children who were not subjected to modified Blalock-Taussig shunts in the past (non-MBTS). Only non-MBTS cyanotic children, but not MBTS-operated patients, showed significantly higher platelet reactivity compared to controls in response to ADP or 1 microM TRAP with respect to P-selectin expression (pchildren and reduced GPIb expression in non-MBTS patients, especially in younger patients, were positively associated with the occurrence of the polymorphic variant Pl(A2) of platelet membrane glycoprotein IIIa gene. Altered blood morphology parameters (elevated RBC, Hb, Hct and MCHC, for all Pchildren correlated with the enhanced degranulation of circulating blood platelets and their hyperreactivity in response to some agonists (Pplatelets are remarkably hyperreactive in non-MBTS cyanotic children, which are at higher risk to often encounter platelets activation in circulation. It seems unlikely that the apparently unchanged platelet reactivity in MBTS-operated children is due to the advantageous effects of the shunt, since these patients showed neither altered haematological parameters nor improved oxygen carrying capacity. Otherwise, it may rather result from more frequent episodes of platelet degranulation and preactivation in the past, and/or post-operative enhanced platelet consumption.

  16. Evaluation of the performance of PRECIL LBY-NJ4A automatic platelet aggregation analyzer%普利生LBY-NJ4A全自动血小板聚集仪性能评价

    Institute of Scientific and Technical Information of China (English)

    石冬敏; 吴元健; 马伟

    2012-01-01

    目的 对普利生LBY-NJ4A全自动血小板聚集仪(NJ4A)进行性能评估.方法 109 mmol/L枸橼酸钠真空管采血,分离富含血小板血浆(PRP)和贫血小板血浆(PPP),应用NJ4A及配套质控品、诱导剂和清洗液,测定血小板最大聚集率(MAR),测试精密度、通道一致性、不确定度、检测限、干扰等.结果 批内不精密度测试,变异系数(CV)为3.4%~5.0%;4个不同通道测定均值差异无统计学意义(P>0.05);携带污染率2.82%;CV批内≤3.5%,CV批间≤4.2%,CV总≤3.8%;总误差范围为5.6%~10.3%,不确定度在可接受范围;2个水平质控品测定值与靶值差异无统计学意义(P>0.05);NJ4A与LBY-NJ2比对结果相关良好(r=0.998,P0.05).结论 NJ4A精密度、准确度、不确定度、灵敏度、携带污染率、抗干扰等性能指标符合CLSI规范,可在临床应用.%Objective To check and evaluate the performance of PRECIL LBY-NJ4A automatic platelet aggregation analyzer (NJ4A) .Methods Blood samples were collected with 109 mmol/L sodium citrate using vacuum tube,then the platelet-rich plasma (PRP)and platelet-poor plasma(PPP) were separated .The NJ4A analyzer with mating quality control,agonists and cleaning solution were used to measure the maximum aggregate rate of platelet (MAR),precision,channel consistency,inaccuracy,detection limitation and inference .Results The precision ranged from 3 .4/0 to 5 .0% .The means of four different channels have no statistically difference(P>0 .05),when carryover rate was 2 .82% .The intra,inter hatch and total coefficient of variance was less than or equal to 3 .5%,4 .2% and 3 .8/0,respectively .The total error ranged from 5 .6/0 to 10 .3%,with an acceptable inaccuracy .Two levels of quality control have no statistically difference with each target value (P>0.05).The correlation of NJ4 and LBY-NJ2 was 0.998 (P0.05) compared to the well-recognized reference range .Conclusion The performance indicators of precision, accuracy, uncertainty

  17. Differential Expression Analysis by RNA-Seq Reveals Perturbations in the Platelet mRNA Transcriptome Triggered by Pathogen Reduction Systems.

    Science.gov (United States)

    Osman, Abdimajid; Hitzler, Walter E; Ameur, Adam; Provost, Patrick

    2015-01-01

    Platelet concentrates (PCs) are prepared at blood banks for transfusion to patients in certain clinical conditions associated with a low platelet count. To prevent transfusion-transmitted infections via PCs, different pathogen reduction (PR) systems have been developed that inactivate the nucleic acids of contaminating pathogens by chemical cross-linking, a mechanism that may also affect platelets' nucleic acids. We previously reported that treatment of stored platelets with the PR system Intercept significantly reduced the level of half of the microRNAs that were monitored, induced platelet activation and compromised the platelet response to physiological agonists. Using genome-wide differential expression (DE) RNA sequencing (RNA-Seq), we now report that Intercept markedly perturbs the mRNA transcriptome of human platelets and alters the expression level of >800 mRNAs (Psystems and control platelets. Of these, 400 genes were deregulated with DE corresponding to fold changes (FC) ≥ 2. At the p-value systems, that target nucleic acids and are not specific to pathogens, for the management of blood products.

  18. Platelet affinity for burro aorta collagen

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, M.D.

    1977-10-01

    Despite ingenious concepts, there are no unequivocal clues as to what, when, and how some undefined biochemical factor(s) or constituent(s) that localizes in the arterial wall can precipitate a thromboatheromatous lesion or arterial disease. The present study focused on the extraction, partial purification, and characterization of a collagen-active platelet stimulator from the aortas of aged burros. The aggregator moiety in the aorta extracts invariably had a higher affinity for platelets in citrated platelet-rich plasma of human beings than for platelets of homologous burros. The platelet-aggregating factor(s) in the aorta extract was retained by incubation with ..cap alpha..-chymotrypsin. Platelet-aggregating activity was rapidly abolished after incubation with collagenase, as determined by platelet-aggregometry tests. Evidence based on light microscope and polysaccharide histochemical reactions indicates a probability that the intracellular amorphous matrix (PAS-positive) and filamentous components (PTAH-positive) expelled from smooth muscle cells disrupted during homogenization of the aorta may be a principal source of a precursor collagen species which is a potent inducer of platelet aggregation.

  19. Morphology and stability of aggregates of an Oxisol according to tillage system and gypsum application

    Directory of Open Access Journals (Sweden)

    Fábio Régis de Souza

    2012-12-01

    Full Text Available Morphological characterization and aggregate stability is an important factor in evaluating management systems. The aim of this paper is to evaluate the stability and morphology of the aggregates of a dystrophic Oxisol managed with no-tillage and conventional tillage with and without the residual action of gypsum. The experimental design was randomized blocks arranged in split-split plot, where the treatments were two soil management systems (plots with 0 and 2000 kg ha-1 of gypsum (subplots and five depths (0-0.05, 0.05-0.10, 0.10-0.15, 0.15-0.20 and 0.20-0.30 m as the subsubplots, with four replications. The aggregate morphology was determined through images and later evaluated by the Quantporo software. Stability was determined by the wet method. The results showed that the no-tillage system, with or without gypsum residual effect, provided the aggregates with the largest geometric diameters. The combination of no-tillage system and the gypsum residual effect provided rougher aggregates.

  20. Platelet reactions to modified surfaces under dynamic conditions.

    Science.gov (United States)

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

    1998-12-01

    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.

  1. Platelet proteomics.

    Science.gov (United States)

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

    2012-01-01

    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.

  2. Performance Evaluation of Carrier Aggregation for Elastic Traffic in LTE-Advanced Systems

    Science.gov (United States)

    Lei, Lei; Zheng, Kan

    Carrier aggregation is a potential technology for the LTE-Advanced system to support wider bandwidth than the LTE system. This paper analyzes the performance of carrier aggregation under elastic traffic, and compares it to that of a simpler approach for the same purpose, referred to as the independent carrier approach. The queueing behaviors of these two approaches are formulated as one fast versus multiple slow state-dependent Processor Sharing servers, respectively. Both analytical and simulation results show that when there are L component carriers with uniform bandwidth in the system, the performance of the carrier aggregation approach is L times better than that of the independent carrier approach in terms of the average user delay and throughput under the same traffic load.

  3. Abacavir induces platelet-endothelium interactions by interfering with purinergic signalling: A step from inflammation to thrombosis.

    Science.gov (United States)

    Alvarez, Angeles; Rios-Navarro, Cesar; Blanch-Ruiz, Maria Amparo; Collado-Diaz, Victor; Andujar, Isabel; Martinez-Cuesta, Maria Angeles; Orden, Samuel; Esplugues, Juan V

    2017-03-02

    The controversy connecting Abacavir (ABC) with cardiovascular disease has been fuelled by the lack of a credible mechanism of action. ABC shares structural similarities with endogenous purines, signalling molecules capable of triggering prothrombotic/proinflammatory programmes. Platelets are leading actors in the process of thrombosis. Our study addresses the effects of ABC on interactions between platelets and other vascular cells, while exploring the adhesion molecules implicated and the potential interference with the purinergic signalling pathway. The effects of ABC on platelet aggregation and platelet-endothelium interactions were evaluated, respectively, with an aggregometer and a flow chamber system that reproduced conditions in vivo. The role of adhesion molecules and purinergic receptors in endothelial and platelet populations was assessed by selective pre-incubation with specific antagonists and antibodies. ABC and carbovir triphosphate (CBT) levels were evaluated by HPLC. The results showed that ABC promoted the adherence of platelets to endothelial cells, a crucial step for the formation of thrombi. This was not a consequence of a direct effect of ABC on platelets, but resulted from activation of the endothelium via purinergic ATP-P2X7 receptors, which subsequently triggered an interplay between P-selectin and ICAM-1 on endothelial cells with constitutively expressed GPIIb/IIIa and GPIbα on platelets. ABC did not induce platelet activation (P-selectin expression or Ca(2+) mobilization) or aggregation, even at high concentrations. CBT levels in endothelial cells were lower than those required to induce platelet-endothelium interactions. Thus, ABC interference with endothelial purinergic signalling leads to platelet recruitment. This highlights the endothelium as the main cell target of ABC, which is in line with previous experimental evidence that ABC induces manifestations of vascular inflammation.

  4. Comparison of inhibitive effect on EDTA-dependent platelet aggregation between two drugs%两种药物对EDTA依赖性血小板聚集的抑制作用比较

    Institute of Scientific and Technical Information of China (English)

    赵凯华; 周雄辉; 刘强; 汪金; 李丽萍; 王科

    2013-01-01

    bjective To investigate the inhibitive effects on EDTA-dependent platelet aggregation between amikacin and ticlopidine in vitro. Methods The XT4800i five classification blood corpuscle analyzer was used to count the blood cells in the complete blood samples added with two anticoagulamt drugs of various concentrations . The counting results were compared with those obtained by manual counting method. Results There were significant differences in PLT counting between amikacin or ticlopidine -anticoagulated samples and EDTA -K2 anticoagulated ones (P 0. 05). The MPV of PLT obtained with anticoagulamt drugs method was samilar to that obtained by the conventional detection (P > 0. 05 ). Conclusion Amikacin and ticlopidine have good inhibitive effects on EDTA-dependent pseudo platelet aggregation , which is suitable for the PLT counting.%目的 探讨阿米卡星、噻氯匹啶两种药物在体外对血小板依赖性聚集的抑制作用.方法 采用XT-1800i五分类血球分析仪,对添加不同药物浓度抗凝血进行计数分析,并与手工法计数结果比较.结果 加入阿米卡星或噻氯匹啶的抗凝管与EDTA-K2抗凝管计数血小板有显著差异(P<0.01),而与手工法比较无显著差异(P>0.05);对于血小板平均体积(MPV)测定与常规测定比较无显著差异(P>0.05).结论 阿米卡星、噻氯匹啶对EDTA依赖性假性血小板聚集具有很好的抑制作用,适用于血小板的测定.

  5. Aggregates morphometry in a Latosol (Oxisol under different soil management systems

    Directory of Open Access Journals (Sweden)

    Carla Eloize Carducci

    2016-02-01

    Full Text Available Changes in soil physical properties are inherent in land use, mainly in superficial layers. Structural alterations can directly influence distribution, stability and especially morphometry of soil aggregates, which hence will affect pore system and the dynamic process of water and air in soil. Among the methods used to measure these changes, morphometry is a complementary tool to the classic methods. The aim of this study was to evaluate structural quality of a Latosol (Oxisol, under different management systems, using morphometric techniques. Treatments consisted of soil under no-tillage (NT; pasture (P, in which both had been cultivated for ten years, and an area under native vegetation (NV – Savannah like vegetation. Aggregates were sampled at depths of 0-0.10 and 0.10-0.20 m, retained on sieves with 9.52 – 4.76 mm, 4.76 – 1.0mm, 1.0 – 0.5mm diameter ranges. Aggregate morphometry was assessed by 2D images from scanner via QUANTPORO software. The analyzed variables were: area, perimeter, aspect, roughness, Ferret diameter and compactness. Moreover, disturbed samples were collected at the same depths to determine particle size, aggregate stability in water, water-dispersible clay, clay flocculation index and organic matter content. It was observed that different soil management systems have modified soil aggregate morphology as well as physical attributes; and management effects’ magnitude increased from NT to P.

  6. Image analysis of blood platelets adhesion.

    Science.gov (United States)

    Krízová, P; Rysavá, J; Vanícková, M; Cieslar, P; Dyr, J E

    2003-01-01

    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.

  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

    1977-07-31

    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 lipidomic.

    Science.gov (United States)

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

    2012-01-01

    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

  9. The Influence of Low Platelet Count on Whole Blood Aggregometry Assessed by Multiplate

    DEFF Research Database (Denmark)

    Stissing, Trine; Dridi, Nadia P; Ostrowski, Sisse R;

    2011-01-01

    The Multiplate, a whole blood (WB) platelet function test, has shown promising results identifying patients on antiplatelet therapy at increased risk of rethrombosis. In the present study, the influence of low platelet count on platelet aggregation was analyzed and compared with aggregation results...... in an artificial matrix, platelet-rich plasma (PRP). Heparinized and citrated blood was diluted with autologous plasma to platelet concentrations 200 to 25 × 10(9)/L in WB samples (n = 10) and 200 to 100 × 10(9)/L in PRP samples (n = 7). The platelet aggregation was investigated by the ADP-, ASPI-, COL-, and TRAP...

  10. Feed the Future Monitoring System Aggregate Data 2011-2014

    Data.gov (United States)

    US Agency for International Development — The Feed the Future Monitoring System (FTFMS) is part of an interagency effort to consolidate U.S. Government (USG) reporting on Feed the Future activities. FTFMS...

  11. Synergism interaction between arachidonic acid by 5-hydroxytryptamine in human platelet aggregation is mediated through multiple signalling pathways%多种信号途径介导花生四烯酸与5-羟色胺在促人类血小板凝集中的协同作用

    Institute of Scientific and Technical Information of China (English)

    Sheikh Arshad SAEED; Huma RASHEED; Anwar-ul-Hassan GILANI

    2003-01-01

    AIM: To examine the signalling mechanisms involved in the synergistic interaction of 5-hydroxytryptamine (5-HT)and arachidonic acid (AA) in human platelet aggregation. METHODS: Blood was obtained from healthy human subjects, mixed with 3.8 % sodium citrate (9:1), and centrifuged to prepare platelet rich plasma (PRP). Aggregation was monitored using a Dual-channel Lumi-aggregometer. The agonist-induced influx of Ca2+ was measured using Fura-2 AM. TXA2 formation was studied using radiochemical method. RESULTS: Subthreshold concentration of 5-HT (2 μmol/L) potentiated the effect of low dose of AA (0.2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC50=5.2 nmol/L; cyproheptadine IC50=0.6 nmol/L), and thromboxane A2 receptor antagonist (SQ 29 548; IC50=30 nmol/L), showing that the effect is receptor-mediated.To examine the down-stream signalling pathways, we found that such an interaction was inhibited by calcium channel blockers (diltiazem; IC50=3 μmol/L and verapamil; IC50=5 μmol/L), phospholipase C (PLC) inhibitor (U73122;IC50=4 μmol/L), cyclooxygenase inhibitor, (indomethacin; IC50=0.2 μmol/L) and mitogen-activated protein (MAP)kinase inhibitor (PD98059; IC50=3 μmol/L). The effect was also inhibited by a specific tyrosine light chain kinase (TLCK) inhibitor, herbimycin A with IC50 value of 5 μmol/L. Pretreatment of platelet with 5-HT and AA induced rise in intracellular calcium and this effect was blocked by verapamil. CONCLUSION: The synergism between 5-HT and AA in platelet aggregation involves activation of PLC/Ca2+, COX, and MAP kinase pathways.

  12. State aggregation and population dynamics in linear systems.

    Science.gov (United States)

    Rowe, Jonathan E; Vose, Michael D; Wright, Alden H

    2005-01-01

    We consider complex systems that are composed of many interacting elements, evolving under some dynamics. We are interested in characterizing the ways in which these elements may be grouped into higher-level, macroscopic states in a way that is compatible with those dynamics. Such groupings may then be thought of as naturally emergent properties of the system. We formalize this idea and, in the case that the dynamics are linear, prove necessary and sufficient conditions for this to happen. In cases where there is an underlying symmetry among the components of the system, group theory may be used to provide a strong sufficient condition. These observations are illustrated with some artificial life examples.

  13. 麒麟菜中多肽的提取及多肽的抗血小板聚集和抗菌活性%Peptides extracted from eucheuma and their activity against platelet aggregation and bacterial growth

    Institute of Scientific and Technical Information of China (English)

    刘彬; 余华军; 伍俊; 崔运忠; 张海涛

    2016-01-01

    was designed to establish a feasible method of purifying polypeptides from eucheuma and investigate their activity against platelet aggre⁃gation and bacterial growth. Methods We extracted peptides from eucheuma with acidic solution, detected the effects of different doses of small molecular polypeptide ( 0, 5, 10, 20, and 40μg/mL) on the growth of Escherichia coli ( D1314) and Staphylococcus aureus (s.agr+, RN4220) using the method of turbidity, and analyzed the anti⁃platelet aggregation activity of the peptides with a whole blood aggregometer. Results The rates of peptides extracted from 50, 100,150, and 200 g of eucheuma were 0.382%, 0.405%, 0.389%, and 0.389%, respectively. The purified sample exhibited a single band on SDS⁃PAGE. The relative molecular weight of the peptides was about 3kD. The extracted peptides inhibited the growth of Escherichia coli, Staphylococcus aureus, and thrombin⁃induced platelet aggregation in a dose⁃dependent manner, with inhibition rates of 44.71%, 51.86%, and 75.00%, respectively. Conclusion The present method can be used to successfully purify low⁃molecular⁃weight peptides from eucheuma and effectively inhibit platelet aggre⁃gation and bacterial growth. The peptides extracted is a potential anti⁃platelet aggregation agent.

  14. In vitro inhibition of platelet aggregation by peptides derived from oat (Avena sativa L.), highland barley (Hordeum vulgare Linn. var. nudum Hook. f.), and buckwheat (Fagopyrum esculentum Moench) proteins.

    Science.gov (United States)

    Yu, Guoyong; Wang, Feng; Zhang, Bolin; Fan, Junfeng

    2016-03-01

    Bioactive compounds present in foods could have beneficial effects on human health. In this study, we report the capacity of peptides released from oat, highland barley, and buckwheat proteins after enzymatic digestion to inhibit platelet aggregation in vitro. All hydrolysates showed high antiplatelet activity, with IC50 values of 0.282mg/ml (oat flour gastrointestinal hydrolysate, 6h) to 2.496mg/ml (highland barley glutelin tryptic hydrolysate, 14h) in a dose-dependent manner. Thirty-eight peptides with more than seven residues were identified in the tryptic hydrolysates of oat globulin. Results of computational modeling revealed that nine peptides, including ALPIDVLANAYR, EFLLAGNNKR, GEEFGAFTPK, QLAQIPR, LQAFEPLR, ALPVDVLANAYR, GEEFDAFTPK, QKEFLLAGNNK, and TNPNSMVSHIAGK bound the cyclooxygenase-1 active centers with low binding energy (-6.5 to -7.5kcal/mol). This is the first report to identify antiplatelet peptides from grain hydrolysates and the binding modes at the molecular level, leading to their possible use as functional food ingredients to prevent thrombosis.

  15. Evaluation of platelet function using multiple electrode platelet aggregometry in dogs with septic peritonitis.

    Science.gov (United States)

    Li, Ronald H L; Chan, Daniel L

    2016-09-01

    To assess platelet function via multiple electrode platelet aggregometry (MEPA) in dogs with septic peritonitis and in healthy dogs. The secondary aim was to determine if there is prognostic significance to changes in platelet function observed in septic dogs. Prospective, observational cohort study conducted from January 2012 to March 2014. University teaching hospital. Twenty dogs with septic peritonitis and 23 healthy dogs. None. MEPA using arachidonic acid, adenosine diphosphate, and collagen (COL) as agonists was measured within 24 hours of diagnosis of sepsis. Compared to healthy dogs, platelet aggregation was reduced in dogs with septic peritonitis for all agonists (P peritonitis. Circulating platelets from dogs with septic peritonitis have diminished aggregation in response to multiple platelet agonists. MEPA may serve as an assessment tool for illness severity in this patient population. © Veterinary Emergency and Critical Care Society 2016.

  16. Stability of lyophilized human platelets loaded with small molecule carbohydrates.

    Science.gov (United States)

    Wang, J X; Yang, C; Wan, W; Liu, M X; Ren, S P; Quan, G B; Han, Y

    2011-01-01

    Long-term preservation of platelets is a great challenge for blood transfusion centers, due to the required narrow storage temperature arange (22 ± 2 degree C). Short shelf life and potential bacterial growth often lead to the shortage of high-quality platelets. Freeze-dried preservation is thus believed to be a potential solution for long-term platelet storage without losing the hemostasis function. Here we report a new platelet preservation method, which uses small molecule carbohydrates to extend storage time and to maintain platelet function. The activities of lyophilized platelets that were stabilized with small molecule carbohydrate (e.g., cell viability, mean platelet volume, activation characteristics, and aggregation kinetics) were maintained after storage of 30, 60, and 90 days at room temperature, 4 degree C, and -20 degree C. The recovery of freeze-dried platelets was 87 percent in comparison to fresh platelets. The mean platelet volume of rehydrated platelets increased (from 6.8 fl to 8.0 fl). About 40 percent of rehydrated platelets was in the early-activated stage (PCA-1 positive) and 30 percent was in the terminal-activated stage (CD62P positive). The cell viability was about 60 percent as measured with CMFDA vital probes. The aggregation rate of rehydrated platelets after 90-day storage was similar to fresh platelets stored at 22 degree C ± 2 degree C.

  17. Evaluation of Mirasol pathogen reduction system by artificially contaminating platelet concentrates with Staphylococcus epidermidis: A pilot study from India

    Directory of Open Access Journals (Sweden)

    Kabita Chatterjee

    2016-01-01

    Full Text Available Background and Objectives: This study was conducted to assess the efficacy of Mirasol pathogen reduction system for platelets aimed at preventing bacterial regrowth by spiking buffy coat pooled platelets (BCPP with clinically relevant load of Staphylococous epidermidis. Materials and Methods: BCPP units were prepared using Teruflex BP-kit with Imugard III-S-PL (Terumo BCT, Tokyo, Japan. Two BCPP units were pooled, of which 40 ml of negative control (NC was removed. The remaining volume of the platelet unit was inoculated with clinically relevant load of bacteria (total of 30 CFU of S. epidermidis in 1 ml; following this the platelet unit was split into two parts. One part served as positive control (PC and the other part was subjected to pathogen reduction technique (Mirasol PRT, CaridianBCT Biotechnologies, Lakewood, CO, USA. Bacterial detection was performed using BacT/ALERT system, controls after day 1 and day 7 following inoculation of bacteria and on day 7 for Mirasol-treated unit. Results: Of the 32 treatment cycles, 28 were valid and 4 were invalid. No regrowth was observed in 96.4% (27 of 28 after treatment with Mirasol pathogen reduction system. Of four invalid tests, on two instances the NC showed growth, whereas in other 2 no regrowth was detected in 7th day PC. Bacterial screening of PCs by BacT/ALERT after 24 h of incubation was 28.6%, whereas the effectiveness increased to 100% when incubated for 7 days. Conclusions: Mirasol system was effective in inactivating S.epidermidis when it was deliberately inoculated into BCPP at clinically relevant concentrations. Such systems may significantly improve blood safety by inactivating traditional and emerging transfusion-transmitted pathogens.

  18. Evaluation of Mirasol pathogen reduction system by artificially contaminating platelet concentrates with Staphylococcus epidermidis: A pilot study from India.

    Science.gov (United States)

    Chatterjee, Kabita; Zaman, Shamsuz; Chaurasia, Rahul; Singh, Surinder; Keil, Shawn D; Tewari, Shalini; Bisht, Akanksha; Agarwal, Nitin; Rout, Diptiranjan; Chand, Subhash; Saha, Kallol

    2016-01-01

    This study was conducted to assess the efficacy of Mirasol pathogen reduction system for platelets aimed at preventing bacterial regrowth by spiking buffy coat pooled platelets (BCPP) with clinically relevant load of Staphylococous epidermidis. BCPP units were prepared using Teruflex BP-kit with Imugard III-S-PL (Terumo BCT, Tokyo, Japan). Two BCPP units were pooled, of which 40 ml of negative control (NC) was removed. The remaining volume of the platelet unit was inoculated with clinically relevant load of bacteria (total of 30 CFU of S. epidermidis in 1 ml); following this the platelet unit was split into two parts. One part served as positive control (PC) and the other part was subjected to pathogen reduction technique (Mirasol PRT, CaridianBCT Biotechnologies, Lakewood, CO, USA). Bacterial detection was performed using BacT/ALERT system, controls after day 1 and day 7 following inoculation of bacteria and on day 7 for Mirasol-treated unit. Of the 32 treatment cycles, 28 were valid and 4 were invalid. No regrowth was observed in 96.4% (27 of 28) after treatment with Mirasol pathogen reduction system. Of four invalid tests, on two instances the NC showed growth, whereas in other 2 no regrowth was detected in 7(th) day PC. Bacterial screening of PCs by BacT/ALERT after 24 h of incubation was 28.6%, whereas the effectiveness increased to 100% when incubated for 7 days. Mirasol system was effective in inactivating S. epidermidis when it was deliberately inoculated into BCPP at clinically relevant concentrations. Such systems may significantly improve blood safety by inactivating traditional and emerging transfusion-transmitted pathogens.

  19. Diffusion-Limited Aggregation in Potato Starch and Hydrogen Borate Electrolyte System

    Directory of Open Access Journals (Sweden)

    Tuhina Tiwari

    2013-01-01

    Full Text Available Natural growth of diffusion-limited aggregate (DLA, without any external stimuli, in boric acid doped starch system is reported here. Fractals grown were confirmed to be of diffusion-limited aggregate (DLA pattern having fractal dimension ~1.49. Effect of substrate and humidity on growth pattern has also been discussed. The existence of a different vibration band of H3BO3 in FTIR confirmed that growth structures are related to boric acid. XRD pattern has shown broad peak along with some sharp peaks. Broad peak is related to starch’s amorphous nature, as where intense sharp peaks are due to boric acid.

  20. Role of dystrophins and utrophins in platelet adhesion process.

    Science.gov (United States)

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

    2006-07-01

    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.

  1. Platelet cytoskeleton and its hemostatic role.

    Science.gov (United States)

    Cerecedo, Doris

    2013-12-01

    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. A system perspective to the deployment of flexibility through aggregator companies

    NARCIS (Netherlands)

    Lampropoulos, I.; van den Broek, M.A.; van Sark, W.G.J.H.M.; van der Hoofd, Erik; Hommes, Klaas

    2016-01-01

    This work focuses on the facilitation of aggregator companies for the provision of flexibility services to the electricity system by using large numbers of dispersed and distributed resources of small capacities. This initiative by TenneT TSO and Utrecht University is about identifying potential

  3. Breakage of the energy equipartition and aggregate formation in sheared system

    Science.gov (United States)

    Baibolatov, Y.; Spahn, F.

    2015-10-01

    In classical thermodynamics any mixture of gases with different masses with any sort of initial temperature differences tend to relax into a stationary state with a unique temperature along the whole system. But this is not true in case of granular mixtures, where energy is dissipated during each collision between particles. As a result, in a granular mixture of species with different masses, the system does not have a unique thermodynamic temperature but each species has its own temperature. This effect has been paid much attention recently [1, 2, 3]. Apart from the dissipative particle interaction, the main reason for this behaviour is due to the mass difference of the colliding particles, causing an asymmetric energy loss of particles. The loss of energy can be compensated by external heating of the system. In the case of planetary rings system, the role of heating is played by gravitational shear caused by the planet. In this work we consider the model consisting of identical spherical and adhesive particles. Although the constituents are identical, they can form aggregates and effectively create particles with larger masses. The differences in masses lead to different velocity dispersions (granular temperatures) of the aggregates. This interplay between heat transfer among aggregates and the distribution of the aggregate sizes under the gravitational shear is of crucial importance for the formulation of mean-field balance equations for the ring particle ensembles.

  4. Data Aggregation in Multi-Agent Systems in the Presence of Hybrid Faults

    Science.gov (United States)

    Srinivasan, Satish Mahadevan

    2010-01-01

    Data Aggregation (DA) is a set of functions that provide components of a distributed system access to global information for purposes of network management and user services. With the diverse new capabilities that networks can provide, applicability of DA is growing. DA is useful in dealing with multi-value domain information and often requires…

  5. Pulsed electric field (PEF)-induced aggregation between lysozyme, ovalbumin and ovotransferrin in multi-protein system.

    Science.gov (United States)

    Wu, Li; Zhao, Wei; Yang, Ruijin; Yan, Wenxu

    2015-05-15

    The aggregation of multi-proteins is of great interest in food processing and a good understanding of the formation of aggregates during PEF processing is needed for the application of the process to pasteurize protein-based foods. The aggregates formation of a multi-protein system (containing ovalbumin, ovotransferrin and lysozyme) was studied through turbidity, size exclusion chromatography and SDS-PAGE patterns for interaction studies and binding forces. Results from size exclusion chromatography indicated that there was no soluble aggregates formed during PEF processing. The existence of lysozyme was important to form insoluble aggregates in the chosen ovalbumin solution. The results of SDS-PAGE patterns indicated that lysozyme was prone to precipitate, and was relatively the higher component of aggregates. Citric acid could be effective in inhibiting lysozyme from interacting with other proteins during PEF processing. Blocking the free sulphydryl by N-ethylmaleimide (NEM) did not affect aggregation inhibition.

  6. Ativação plaquetária na esclerose sistêmica e alternativas metodológicas para sua avaliação Platelet activation in systemic sclerosis and methodological options to its assessment

    Directory of Open Access Journals (Sweden)

    Paulo Sergio Massabki

    2004-02-01

    immunologic abnormalities. The microangiopathic aspect is responsible for the most severe and life-threatening features of the disease. The interaction between endothelium and platelets plays an important role in the pathophysiology of SSc. Evidence of platelet activation in SSc includes high plasma levels of platelet-derived substances (Von Willenbrand factor, platelet factor 4, thromboxane A2, and ß-thromboglobulin, circulating platelet aggregates, ultra structural abnormalities in platelets, and the presence of platelets adhered to the endothelium. This review addresses the principles and possible pitfalls of the main methods for evaluation of platelet activation and function. The assessment of the ability of platelet aggregation is performed with and without the addition of agonists (adenosine diphosphate, collagen, adrenaline. Platelet activation may be assessed by two ways: by measurement of plasma concentration of substances that are released as the platelets are activated (e.g., thromboxane, platelet factor 4 and by the measurement of membrane expression of molecules that are transported to the platelet membrane during the activation process (e.g., GMP-140, glycoprotein IIb/IIIa. A recent contribution to this field was the demonstration that neuron-specific enolase (NSE is released from the platelets into the blood in patients with active SSc. NSE, which is readily available in clinical laboratories with emphasis in tumor markers, may become a useful platelet activation marker in a series of clinical conditions.

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

    OpenAIRE

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

    2012-01-01

    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...

  8. Platelet scintigraphy in atherothrombotic disease

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Yoshinari (Osaka National Hospital (Japan))

    1993-01-01

    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).

  9. Calpain Activator Dibucaine Induces Platelet Apoptosis

    Directory of Open Access Journals (Sweden)

    Jun Liu

    2011-03-01

    Full Text Available Calcium-dependent calpains are a family of cysteine proteases that have been demonstrated to play key roles in both platelet glycoprotein Ibα shedding and platelet activation and altered calpain activity is associated with thrombotic thrombocytopenic purpura. Calpain activators induce apoptosis in several types of nucleated cells. However, it is not clear whether calpain activators induce platelet apoptosis. Here we show that the calpain activator dibucaine induced several platelet apoptotic events including depolarization of the mitochondrial inner transmembrane potential, up-regulation of Bax and Bak, down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation and phosphatidylserine exposure. Platelet apoptosis elicited by dibucaine was not affected by the broad spectrum metalloproteinase inhibitor GM6001. Furthermore, dibucaine did not induce platelet activation as detected by P-selectin expression and PAC-1 binding. However, platelet aggregation induced by ristocetin or α-thrombin, platelet adhesion and spreading on von Willebrand factor were significantly inhibited in platelets treated with dibucaine. Taken together, these data indicate that dibucaine induces platelet apoptosis and platelet dysfunction.

  10. Research of the relevance with storage temperature fluctuations on the frozen platelet occurrence of irreversible aggregation%贮存温度波动与冰冻血小板不可逆聚集发生的相关性研究

    Institute of Scientific and Technical Information of China (English)

    李交; 夏传友; 贾璋林

    2009-01-01

    Objective Discussion on the relevance of the frozen platelet preservation during temperature fluctuations with the frozen platelet occurrence irreversible aggregation.Methods During 2006-2008,a total of 1 842 bags of frozen platelets preservation and melting data were statistically analysed,and the relevance of the frozen platelets preservation during temperature fluctuations with the occurrence of platelet irreversible aggregation after resuscitative melting were investigated.Results The frozen platelets storage temperature between -80 ℃ and -60 ℃ and -80 ℃ and -50 ℃ range of fluctuation,the platelets after melt resuscitative occurrence irreversible aggregation were 6.39% and 31.21%.Compared the two observation groups with the control group(preservation temperature between -80 ℃ and -70 ℃ range of fluctuation),there were significant differences(P<0.01).Under the preservation temperature between -80 ℃ and -50 ℃ range of fluctuation,apheresis platelets and concentrate platelets after melt resuscitative,apheresis platelet occurrence irreversible aggregation was 72.97%,the concentrate platelet occurrence irreversible aggregation was 18.33%. Compared the two groups,there were significant difference (χ2=39.33,P<0.01);under preservation temperature between -80 ℃ and -60 ℃ range of fluctuation,apheresis platelet and concentrate platelet after melt resuscitative,there were no significant difference(χ2=0.89,P>0.05).Conclusion Under preservation temperature between -80 ℃ and -60 ℃ and between -80 ℃ and -50 ℃ range of fluctuation,the platelet after melt resuscitative occurrence irreversible aggregation,incidence could occur often.Under preservation temperature between -80 ℃ and -70 ℃ range of fluctuation,the platelet after melt resuscitative occurrence irreversible aggregation,there is few incidence.Temperature range between -80 ℃ and -70 ℃ can be used as the current Blood Bank of frozen platelet reference temperature choice

  11. Aggregation Analysis for Competitive Multiagent Systems With Saddle Points via Switching Strategies.

    Science.gov (United States)

    Zhu, Liying; Xiang, Zhengrong

    2017-06-16

    This paper addresses the aggregation issues of competitive multiagent systems (CMASs) consisting of competitive agents with multimodes and saddle points. In such CMASs, due to existing mutual competitions, every agent is equipped with finite multimodes, and every mode in any agent is described as a second-order linear time-invariant (LTI) control system. When the origin is the same saddle point of all modes of agents, to investigate aggregation of the CMASs with switching strategies, we first use switched LTI systems with saddle points to formulate such CMASs. Then, two new stability concepts, called initial-state-dependent ISD) stability and initial-state-independent (ISI) stability, are defined for the CMASs. Based on these new stability concepts, a practical criterion of local/global ISI asymptotic aggregation is proposed for the CMASs. A local/global ISD/ISI asymptotical-stabilizing-control observed as distributed controls of multimodes, stabilizing-switching-paths, and a corresponding algorithm are all designed for local/global aggregation of such CMASs with switching delays. Finally, a numerical example illustrates the effectiveness and practicality of our new results.

  12. Fusaric acid, a mycotoxin, and its influence on blood coagulation and platelet function.

    Science.gov (United States)

    Devaraja, Sannaningaiah; Girish, Kesturu S; Santhosh, Martin S; Hemshekhar, Mahadevappa; Nayaka, Siddaiah C; Kemparaju, Kempaiah

    2013-06-01

    The current study intended to explore the effect of fusaric acid on blood coagulation including plasma coagulation and platelet aggregation. Fusaric acid exhibited biphasic effects on citrated human plasma recalcification time. At concentrations below 50 ng, fusaric acid decreased the clotting time of plasma dose-dependently from 130 ± 3s control value to 32 ± 3s; however, above 50 ng, fusaric acid increased the clotting time from 32 ± 3s and reached a maximum of 152 s at 100 ng and remained unaltered thereafter for the increased dose of fusaric acid. Fusaric acid without damaging red blood cells and platelets, inhibited agonists such as collagen, ADP, thrombin, and epinephrine-induced aggregation of both platelet-rich plasma (PRP) and washed platelets preparations of human. Interestingly, fusaric acid showed biphasic effects only in thrombin-induced platelet aggregation of washed platelets, and at lower concentration (below 900 ng) it activated platelet aggregation; however, in increased concentration (above 900 ng) it inhibited the platelet aggregation of washed platelets. In addition, fusaric acid also inhibited the agonist ADP-induced platelet aggregation of washed platelet suspension but did not show biphasic effect. Further, fusaric acid did not induce the platelets to generate reactive oxygen species (ROS) that clearly suggests that the induction of platelet function could be the result of the fusaric acid-mediated receptor interaction but not through the morphological shape change.

  13. Acquired platelet function defect

    Science.gov (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 ...

  14. Platelet Donation

    Science.gov (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 ...