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Sample records for adp-induced platelet aggregation

  1. Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors.

    Science.gov (United States)

    Olivier, Christoph B; Weik, Patrick; Meyer, Melanie; Weber, Susanne; Diehl, Philipp; Bode, Christoph; Moser, Martin; Zhou, Qian

    2016-08-01

    Dabigatran and rivaroxaban are novel, vitamin K-independent oral anticoagulants (NOACs) and act via antagonism of the coagulation factor (F) IIa (dabigatran) or FXa (rivaroxaban), respectively. Compared to vitamin-K-antagonists, NOACs have shown non-inferiority of risk and benefit in patients with non valvular atrial fibrillation (AF). In clinical practice there is increasing use of NOACs combined with platelet inhibitors in patients with AF and coronary artery disease. However, whether NOACs affect the function of platelet inhibitors remains incompletely known. This observational study aimed to assess the platelet function in patients receiving dabigatran or rivaroxaban and concomitant platelet inhibitors. A single centre observational study was performed analysing the platelet aggregation of patients treated with dabigatran or rivaroxaban with or without concomitant platelet inhibitors. Measurements before the initiation of NOAC therapy served as the respective control group. Platelet aggregation was measured by multiple electrode aggregometry and was induced with adenosine diphosphate (ADP, 6.5 µM) and arachidonic acid (AA, 0.5 mM), respectively. In order to evaluate whether NOACs interact with platelet inhibition by ASA or the P2Y12-antagonist clopidogrel, 87 patients were grouped according to their concomitant antiplatelet medication. Comparing the ADP- and AA-induced platelet aggregation in patients without concomitant platelet inhibitors (n = 45) no significant differences under therapy with dabigatran (d) or rivaroxaban (r) compared to the control group (c) were observed. In patients taking clopidogrel as a concomitant platelet inhibitor (n = 21), neither dabigatran nor rivaroxaban affected the ADP-induced platelet aggregation (c 20 ± 11, d 21 ± 14, r 18 ± 8 AU*min, p = 0.200). Patients receiving dabigatran or rivaroxaban in combination with ASA (n = 42; 21 ASA only, 21 ASA + clopidogrel) showed no significant differences of the AA

  2. Effects of oral contraceptives, or lanosterol, on ADP-induced aggregation and binding of 125I-fibrinogen to rat platelets

    International Nuclear Information System (INIS)

    The aggregation to ADP and the binding of 125I-fibrinogen to platelets from rats treated with oral contraceptives or normal platelets treated in vitro with lanosterol were compared to their respective controls. Both types of platelets showed a significant increase in ADP-induced aggregation and in binding of fibrinogen, indicating that the effect of oral contraceptives could be partly due to increased levels of lanosterol in platelet membrane

  3. Inhalation of nitric oxide inhibits ADP-induced platelet aggregation and alpha-granule release.

    Science.gov (United States)

    Hagberg, I A; Sølvik, U Ø; Opdahl, H; Roald, H E; Lyberg, T

    1999-01-01

    To gather further information about the effects on blood platelet activation of in vivo exposure to nitric oxide (NO), platelet reactivity was studied in blood from healthy, non-smoking male volunteers before and after 30 min inhalation of 40 ppm NO. Whole blood was stimulated in vitro with adenosine diphosphate or thrombin receptor activation peptide (TRAP-6). In an ex vivo perfusion model, non-anticoagulated blood was exposed to immobilised collagen at arterial blood flow conditions (2600 s(-1)). Blood samples from both the in vitro and ex vivo experiments were stained with fluorochrome-labelled Annexin-V and antibodies against CD42a, CD45, CD49b, CD61, CD62P and fibrinogen, and analysed with a three-colour flow cytometry technique. NO inhalation reduced the platelet activation response to adenosine diphosphate (ADP) stimulation by decreasing platelet-platelet aggregation, alpha-granule release and platelet-leukocyte conjugate formation. TRAP-stimulated platelet activation, collagen-induced platelet activation and thrombus growth was unaffected by NO inhalation. We therefore suggest an ADP receptor inhibitor mode of action of inhaled NO, selective on the newly suggested G protein- and phospholipase C-coupled P2Y1 receptor. Our results demonstrate that blood platelet activation in healthy subjects is modulated by inhalation of NO in therapeutically relevant doses, although the clinical impact of our findings remains unclear. PMID:16801117

  4. Effects of dietary linoleic acid on rat platelet ADP-induced aggregation and binding of 125I-fibrinogen

    International Nuclear Information System (INIS)

    Platelets from rats fed a diet high in linoleic acid (6%) bound increased amounts of fibrinogen on stimulation with ADP, compared to those from rats fed diets with low (2%) or no linoleic acid. However, this increased fibrinogen binding was associated with a decrease in platelet aggregation induced by ADP. Changes in the linoleic acid concentration in platelet membranes may cause changes in this relationship

  5. COX-2 Inhibition by Use of Rofecoxib or High Dose Aspirin Enhances ADP-Induced Platelet Aggregation in Fresh Blood

    OpenAIRE

    Borgdorff, P.; Handoko, M.L.; Wong, Y.Y.; Tangelder, G.J.

    2010-01-01

    Aim: Increased cardiovascular risk after use of selective or nonselective cyclooxygenase-2 (COX-2)-inhibitors might partly be caused by enhanced platelet aggregability. However, an effect of COX-2 inhibition on platelets has so far not been observed in humans. Methods: We tested in healthy volunteers the effect of COX-2-inhibition nearly in-vivo, i.e. immediately after and even during blood sampling. Results: Measurement within 2 minutes after venipuncture, but not 60 minutes later, showed th...

  6. Relationships between optical aggregometry (type Born) and flow cytometry in evaluating ADP-induced platelet activation

    OpenAIRE

    Sbrana, Silverio; Della Pina, Francesca; Rizza, Antonio; Buffa, Manuela; De Filippis, Rossella; Gianetti, Jacopo; Clerico, Aldo

    2008-01-01

    Background: Platelet response to activating agents is used to monitor the efficacy of anti-aggregation therapies. The aim of our study has been to demonstrate the existence of relationships between early events of ADP-induced platelet activation, measured by flow cytometry and platelet-rich plasma aggregation,quantified by optical aggregometry. Methods: We evaluated peripheral blood of 12 donors. The following parameters were quantified by cytometry after stimulation with adenosine diphosphat...

  7. Isolation and characterization of two disintegrins inhibiting ADP-induced human platelet aggregation from the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake)

    International Nuclear Information System (INIS)

    Disintegrins and disintegrin-like proteins are molecules found in the venom of four snake families (Atractaspididae, Elapidae, Viperidae, and Colubridae). The disintegrins are nonenzymatic proteins that inhibit cell-cell interactions, cell-matrix interactions, and signal transduction, and may have potential in the treatment of strokes, heart attacks, cancers, and osteoporosis. Prior to 1983, the venom of Crotalus scutulatus scutulatus (Mohave Rattlesnake) was known to be only neurotoxic; however, now there is evidence that these snakes can contain venom with: (1) neurotoxins; (2) hemorrhagins; and (3) both neurotoxins and hemorrhagins. In this study, two disintegrins, mojastin 1 and mojastin 2, from the venom of a Mohave rattlesnake collected in central Arizona (Pinal County), were isolated and characterized. The disintegrins in these venoms were identified by mass-analyzed laser desorption ionization/time-of-flight/time-of-flight (MALDI/TOF/TOF) mass spectrometry as having masses of 7.436 and 7.636 kDa. Their amino acid sequences are similar to crotratroxin, a disintegrin isolated from the venom of the western diamondback rattlesnake (C. atrox). The amino acid sequence of mojastin 1 was identical to the amino acid sequence of a disintegrin isolated from the venom of the Timber rattlesnake (C. horridus). The disintegrins from the Mohave rattlesnake venom were able to inhibit ADP-induced platelet aggregation in whole human blood both having IC5s of 13.8 nM, but were not effective in inhibiting the binding of human urinary bladder carcinoma cells (T24) to fibronectin

  8. Platelet aggregation test

    Science.gov (United States)

    The platelet aggregation blood test checks how well platelets , a part of blood, clump together and cause blood to clot. ... Decreased platelet aggregation may be due to: Autoimmune ... Fibrin degradation products Inherited platelet function defects ...

  9. Effects of hydrocortisone and aminophylline on the aggregation of equine platelets in vitro

    OpenAIRE

    Casella, Stefania; Giudice, Elisabetta; Giannetto, Claudia; Marafioti, Simona; Piccione, Giuseppe

    2011-01-01

    The purpose of this study was to evaluate in vitro the effects of hydrocortisone and aminophylline on adenosine diphosphate (ADP)-induced platelet aggregation in horses. Blood samples from 30 healthy Thoroughbred horses were collected by via jugular venipuncture to assess platelet aggregation. Platelet-rich and platelet-poor plasma were prepared from all samples by centrifugation and divided into three different aliquots. In the first aliquot, platelet aggregation was measured after platelet ...

  10. The Ratio of ADP- to TRAP-Induced Platelet Aggregation Quantifies P2Y12-Dependent Platelet Inhibition Independently of the Platelet Count

    OpenAIRE

    Olivier, Christoph B.; Meyer, Melanie; Bauer, Hans; Schnabel, Katharina; Weik, Patrick; Zhou, Qian; Bode, Christoph; Moser, Martin; Diehl, Philipp

    2016-01-01

    Objective This study aimed to assess the association of clinical factors with P2Y12-dependent platelet inhibition as monitored by the ratio of ADP- to TRAP-induced platelet aggregation and conventional ADP-induced aggregation, respectively. Background Controversial findings to identify and overcome high platelet reactivity (HPR) after coronary stent-implantation and to improve clinical outcome by tailored anti-platelet therapy exist. Monitoring anti-platelet therapy ex vivo underlies several ...

  11. The Effect of Butanolides from Cinnamomum tenuifolium on Platelet Aggregation

    OpenAIRE

    Chung-Yi Chen; Sheue-Jiun Chen; Hui-Ming Wu; Huei-Ping Dong

    2013-01-01

    This study investigated the effects of isotenuifolide and tenuifolide B from the stems of Cinnamomum tenuifolium on adenosine diphosphate (ADP)-induced human platelet aggregation. Treatment of human platelet-rich plasma with isotenuifolide (1 and 2 μg/μL) and tenuifolide B (1, 2 and 4 μg/μL) did not have any significant effect on human platelet aggregation in vitro, however, treatment of human platelet-rich plasma with isotenuifolide (4 μg/μL) resulted in an inhibitory effect on platelet aggr...

  12. Plant extracts inhibit ADP-induced platelet activation in humans: their potential therapeutic role as ADP antagonists.

    Science.gov (United States)

    Jagroop, Indera Anita

    2014-01-01

    Adenosine diphosphate (ADP) plays a pivotal role in platelet activation. Platelet hyperactivity is associated with vascular disease and also has a key role in haemostasis and thrombosis. ADP activates platelets through three purinoceptor subtypes, the G(q)-coupled P2Y(1) receptor, G(i)-coupled P2Y(12) receptor and P2X(1) ligand-gated cation channel. Platelet ADP purinergic receptors are therefore suitable targets for antiplatelet drugs. Thienopyridines such as clopidogrel and ticlopidine, as well as other ADP receptor antagonists like prasugrel, ticagrelor, cangrelor and elinogrel have demonstrated clinical benefits via the inhibition of the selective purinergic ADP receptor, P2Y(12). However, they still have limitations in their mode of action and efficacy, like increased risk of bleeding. Thus, the ongoing pursuit to develop newer and more effective antiplatelet agents continues. There is a growing interest in the purinergic antiplatelet properties exhibited by plant extracts. This article considers the following: pomolic acid isolated from Licania pittieri, brazilin isolated from the heartwood of Caesalpinia sappan L, phylligenin isolated from the twigs of Muraltia vulpina, bark oil of Gonystylus velutinus, seed and bark extracts from Aesculus hippocastanum L. and red wine phenolics and catechins isolated from green tea. Moreover, the method used to investigate platelet purinergic receptors should be considered, since using a more sensitive, high-resolution platelet sizer can sometimes detect platelet variations when the light transmission method was not able to do so. The exact mechanisms by which these plant extracts work need further investigation. They all however inhibit ADP-induced activation in human platelets. This could explain, at least in part, the protective effect of plant extracts as antiplatelet agents. PMID:24190032

  13. The effects of vincristine on platelet aggregation studied by a filter loop technique in the rat.

    OpenAIRE

    Bee, D; Leach, E.; Martin, J. F.; Suggett, A. J.

    1980-01-01

    1 A method for measuring aggregation of platelets of adenosine diphosphate (ADP) is described using a filter inserted into the flowing aortic blood in the rat. 2 Repeated infusions of ADP resulted in a fall in the calculated aggregation index without significant changes in the platelet count. 3 Vincristine (0.05 mg/kg) intravenously caused significant inhibition of ADP-induced platelet aggregation. 4 Infusion of ADP caused some peripheral vasodilatation though it is unlikely that this contrib...

  14. Adenosine-mediated inhibition of platelet aggregation by acadesine. A novel antithrombotic mechanism in vitro and in vivo.

    OpenAIRE

    Bullough, D A; Zhang, C.; Montag, A; Mullane, K. M.; Young, M A

    1994-01-01

    Inhibition of platelet aggregation by acadesine was evaluated both in vitro and ex vivo in human whole blood using impedance aggregometry, as well as in vivo in a canine model of platelet-dependent cyclic coronary flow reductions. In vitro, incubation of acadesine in whole blood inhibited ADP-induced platelet aggregation by 50% at 240 +/- 60 microM. Inhibition of platelet aggregation was time dependent and was prevented by the adenosine kinase inhibitor, 5'-deoxy 5-iodotubercidin, which block...

  15. Platelet activation and aggregation

    DEFF Research Database (Denmark)

    Jensen, Maria Sander; Larsen, O H; Christiansen, Kirsten; Fenger-Eriksen, C; Ingerslev, J; Sørensen, Benny

    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...... by tissue factor evaluated by means of impedance aggregometry. Citrated whole blood from healthy volunteers and haemophilia A patients with the addition of inhibitors of the contact pathway and fibrin polymerization was evaluated. In healthy persons, a second wave of platelet aggregation was found to...... coincide with the thrombin burst and to be abolished by thrombin inhibitors. In this system, platelet aggregation in severe haemophilia A (n = 10) was found to be significantly decreased as compared with healthy individuals (912 ± 294 vs. 1917 ± 793 AU × min, P = 0.003), most probably due to the weak level...

  16. Glycine reduces platelet aggregation

    OpenAIRE

    Schemmer, Peter; Zhong, Zhi; Galli, Uwe; Wheeler, Michael D.; Xiangli, Li; Bradford, Blair U.; Conzelmann, Lars O.; Forman, Dow; Boyer, José; Thurman, Ronald G

    2012-01-01

    It has been demonstrated that a wide variety of white blood cells and macrophages (i.e. Kupffer cells, alveolar and peritoneal macrophages and neutrophils) contain glycine-gated chloride channels. Binding of glycine on the receptor stimulates Cl− influx causing membrane hyperpolarization that prevents agonist-induced influx of calcium. Since platelet-aggregation is calcium-dependent, this study was designed to test the hypothesis that glycine would inhibit platelet aggregation. Rats were fed ...

  17. Taurine and platelet aggregation

    International Nuclear Information System (INIS)

    Taurine is a putative neurotransmitter or neuromodulator. The endogenous taurine concentration in human platelets, determined by amino acid analysis, is 15 μM/g. In spite of this high level, taurine is actively accumulated. Uptake is saturable, Na+ and temperature dependent, and suppressed by metabolic inhibitors, structural analogues, and several classes of centrally active substances. High, medium and low affinity transport processes have been characterized, and the platelet may represent a model system for taurine transport in the CNS. When platelets were incubated with 14C-taurine for 30 minutes, then resuspended in fresh medium and reincubated for one hour, essentially all of the taurine was retained within the cells. Taurine, at concentrations ranging from 10-1000 μM, had no effect on platelet aggregation induced by ADP or epinephrine. However, taurine may have a role in platelet aggregation since 35-39% of the taurine taken up by human platelets appears to be secreted during the release reaction induced by low concentrations of either epinephrine or ADP, respectively. This release phenomenon would imply that part of the taurine taken up is stored directly in the dense bodies of the platelet

  18. 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...

  19. 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.

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

    International Nuclear Information System (INIS)

    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 α-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. (Auth.)

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

    International Nuclear Information System (INIS)

    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 destruct these photoproducts in the dark after irradiation. Lipid antioxidants α-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. (Auth.)

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

    International Nuclear Information System (INIS)

    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 [1-14C]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. (author)

  3. Correlation between increased platelet ADP aggregability and silent brain infarcts

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the correlation between platelet aggregability and silent brain infarcts. The study subjects were 445 people (264 men, 181 women; mean age, 53±14 years) with no neurologic signs, history of brain tumor, trauma, cerebrovascular disease, or antiplatelet medications. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by the aggregation-size analytic method. Platelet aggregability was classified into 9 classes. The presence of headache/vertigo, hypertension, diabetes mellitus, hyperlipidemia, or smoking was elicited by questioning or blood sampling. A head MRI scan was performed, and if marked atherosclerosis or obvious stenosis in the intracranial vessels was detected, it was defined as a positive MR angiography (MRA) finding. Silent brain infarcts were detected in 26.3% of subjects. Hyperaggregability defined as that above class 6, 7, and 8 was present in 43.8%, 30.8%, and 15.7% of subjects, respectively. The risk factors for silent brain infarcts by multiple logistic regression analysis were aging, hypertension, positive MRA findings, and hyperaggregability. Platelet ADP hyperaggregability might be a risk factor for silent brain infarcts. (author)

  4. Antipsychotic Drugs Inhibit Platelet Aggregation via P2Y1 and P2Y12 Receptors

    Science.gov (United States)

    Wu, Chang-Chieh; Tsai, Fu-Ming; Chen, Mao-Liang; Wu, Semon; Lee, Ming-Cheng; Tsai, Tzung-Chieh; Wang, Lu-Kai; Wang, Chun-Hua

    2016-01-01

    Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM). Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, and that clot firmness was decreased in platelets pretreated with APDs. We also examined the role two major adenosine diphosphate (ADP) receptors, P2Y1 and P2Y12, play in ADP-mediated platelet activation and APD-mediated suppression of platelet aggregation. Our results show that P2Y1 receptor stimulation with ADP-induced calcium influx was inhibited by APDs in human and rats' platelets, as assessed by in vitro or ex vivo approach, respectively. In contrast, APDs, risperidone and clozapine, alleviated P2Y12-mediated cAMP suppression, and the release of thromboxane A2 and arachidonic acid by activated platelets decreased after APD treatment in human and rats' platelets. Our data demonstrate that each APD tested significantly suppressed platelet aggregation via different mechanisms. PMID:27069920

  5. A revised model of platelet aggregation

    OpenAIRE

    Kulkarni, Suhasini; Dopheide, Sacha M.; Yap, Cindy L.; Ravanat, Catherine; Freund, Monique; Mangin, Pierre; Heel, Kathryn A.; Street, Alison; Harper, Ian S.; Lanza, Francois; Jackson, Shaun P.

    2000-01-01

    In this study we have examined the mechanism of platelet aggregation under physiological flow conditions using an in vitro flow-based platelet aggregation assay and an in vivo rat thrombosis model. Our studies demonstrate an unexpected complexity to the platelet aggregation process in which platelets in flowing blood continuously tether, translocate, and/or detach from the luminal surface of a growing platelet thrombus at both arterial and venous shear rates. Studies of platelets congenitally...

  6. Inhibition of platelet aggregation and 5-HT release by extracts of Australian plants used traditionally as headache treatments.

    Science.gov (United States)

    Rogers, K L; Grice, I D; Griffiths, L R

    2000-02-01

    To identify potential migraine therapeutics, extracts of eighteen plants were screened to detect plant constituents affecting ADP induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of the seven plants exhibiting significant inhibition of platelet function were reanalysed in the presence of polyvinyl pyrrolidone (PVP) to remove polyphenolic tannins that precipitate proteins. Two of these extracts no longer exhibited inhibition of platelet activity after removal of tannins. However, extracts of Crataegus monogyna, Ipomoea pes-caprae, Eremophila freelingii, Eremophila longifolia, and Asteromyrtus symphyocarpa still potently inhibited ADP induced human platelet [14C]5-HT release in vitro, with levels ranging from 62 to 95% inhibition. I. pes-caprae, and C. monogyna also caused significant inhibition of ADP induced platelet aggregation. All of these plants have been previously used as traditional headache treatments, except for C. monogyna which is used primarily for protective effects on the cardiovascular system. Further studies elucidating the compounds that are responsible for these anti-platelet effects are needed to determine their exact mechanism of action. PMID:10664475

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Papasian Christopher J

    2011-04-01

    .7 μg/mL in plasma and 3.8 vs 3.9 μg/mL in platelets. Conclusions The present results indicate that intravenously administered tocotrienols inhibited acute platelet-mediated thrombus formation, and collagen and ADP-induced platelet aggregation. α-Tocotrienols treatment induced increases in α-tocopherol levels of 4-fold and 6-fold in plasma and platelets, respectively. Interestingly, tocotrienols (TRF treatment induced a less pronounced increase in the levels of tocotrienols in plasma and platelets, suggesting that intravenously administered tocotrienols may be converted to tocopherols. Tocotrienols, given intravenously, could potentially prevent pathological platelet thrombus formation and thus provide a therapeutic benefit in conditions such as stroke and myocardial infarction.

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

    International Nuclear Information System (INIS)

    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 [3H]serotonin, or alter the dose-responsive binding of 125I-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. Spontaneous intravascular platelet aggregation in angiographic studies

    International Nuclear Information System (INIS)

    The process of intravascular platelet aggregation is activated in angiographic clinical studies using 76% Verografin solution. It has been shown in experiments op rats that verografin (2 ml/kg) and iodamide (2 ml/ kg) together with the activation of intravascular platelet aggregation inhibit antiaggregation properties of the vascular wall

  11. 21 CFR 864.5700 - Automated platelet aggregation system.

    Science.gov (United States)

    2010-04-01

    ... 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 aggregation system is a device used to determine changes in platelet shape and platelet aggregation following...

  12. Platelet aggregation in platelet suspensions from Mongolian gerbils (Meriones unguiculatus).

    OpenAIRE

    Agwu, D E; Holub, B J; Johnstone, I. B.; Crane, S.

    1983-01-01

    Blood obtained from Mongolian gerbils (Meriones unguiculatus) by cardiac puncture was used to develop a method for preparing platelet suspensions suitable for biochemical and aggregometric studies. The aggregation responses of gerbil platelet suspensions to 10 microM adenosine diphosphate and to 0.2 U/mL thrombin were immediate and irreversible. In addition, thrombin produced a short lag period. Bovine acid-soluble collagen (1:800) produced a long lag period coupled with an irreversible aggre...

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

    OpenAIRE

    Maria José Dantas Coêlho; Taysa de Castro Monteiro; Felicien Gonçalves Vasquez; Kátia Luz Torres Silva; Kleber Sandro Brasil dos Santos; Viviana Maria Araújo de Oliveira; Francimary de Oliveira Cavalcante

    2011-01-01

    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...

  14. Inhibitory effects of kiwifruit extract on human platelet aggregation and plasma angiotensin-converting enzyme activity.

    Science.gov (United States)

    Dizdarevic, Lili L; Biswas, Dipankar; Uddin, M D Main; Jørgenesen, Aud; Falch, Eva; Bastani, Nasser E; Duttaroy, Asim K

    2014-01-01

    Previous human studies suggest that supplementation with kiwifruits lowers several cardiovascular risk factors such as platelet hyperactivity, blood pressure and plasma lipids. The cardiovascular health benefit of fruit and vegetables is usually attributed to the complex mixture of phytochemicals therein; however, kiwifruit's cardioprotective factors are not well studied. In this study, we investigated the effects of kiwifruit extract on human blood platelet aggregation and plasma angiotensin-converting enzyme (ACE) activity. A sugar-free, heat-stable aqueous extract with molecular mass less than 1000 Da was prepared from kiwifruits. Typically, 100 g kiwifruits produced 66.3 ± 5.8 mg (1.2 ± 0.1 mg CE) of sugar-free kiwifruit extract (KFE). KFE inhibited both human platelet aggregation and plasma ACE activity in a dose-dependent manner. KFE inhibited platelet aggregation in response to ADP, collagen and arachidonic acid, and inhibitory action was mediated in part by reducing TxA2 synthesis. The IC50 for ADP-induced platelet aggregation was 1.6 ± 0.2 mg/ml (29.0 ± 3.0 μg CE/ml), whereas IC50 for serum ACE was 0.6 ± 0.1 mg/ml (11.0 ± 1.2 μg CE/ml). Consuming 500 mg of KFE (9.0 mg CE) in 10 g margarine inhibited ex vivo platelet aggregation by 12.7%, 2 h after consumption by healthy volunteers (n = 9). All these data indicate that kiwifruit contains very potent antiplatelet and anti-ACE components. Consuming kiwifruits might be beneficial as both preventive and therapeutic regime in cardiovascular disease. PMID:24219176

  15. 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.

  16. Analysis of aggregation of platelets in thrombosis

    Science.gov (United States)

    Ahuja, Suresh

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

  17. Effects of platelet inhibitors on propyl gallate-induced platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activation.

    Science.gov (United States)

    Xiao, Hongyan; Kovics, Richard; Jackson, Van; Remick, Daniel G

    2004-04-01

    Propyl gallate (PG) is a platelet agonist characterized by inducing platelet aggregation, protein tyrosine phosphorylation, and platelet factor 3 activity. The mechanisms of platelet activation following PG stimulation were examined by pre-incubating platelets with well-defined platelet inhibitors using platelet aggregation, protein tyrosine phosphorylation, activated plasma clotting time, and annexin V binding by flow cytometry. PG-induced platelet aggregation and tyrosine phosphorylation of multiple proteins were substantially abolished by aspirin, apyrase, and abciximab (c7E3), suggesting that PG is associated with activation of platelet cyclooxygenase 1, adenosine phosphate receptors, and glycoprotein IIb/IIIa, respectively. The phosphorylation of the cytoskeletal enzyme pp60(c-src) increased following PG stimulation, but was blunted by pre-incubation of platelets with aspirin, apyrase, and c7E3, suggesting that tyrosine kinase is important for the signal transduction of platelet aggregation. Propyl gallate also activates platelet factor 3 by decreasing the platelet coagulation time and increasing platelet annexin V binding. Platelet incubation with aspirin, apyrase, and c7E3 did not alter PG-induced platelet coagulation and annexin V binding. The results suggest that platelet factor 3 activation and membrane phosphotidylserine expression were not involved with activation of platelet cyclooxygenase, adenosine phosphate receptors, and glycoprotein IIb/IIIa. PG is unique in its ability to stimulate platelet aggregation and coagulation simultaneously, and platelet inhibitors in this study affect only platelet aggregation but not platelet coagulation. PMID:15060414

  18. Synthesis of nitric oxide releasing, vasodilating and platelet aggregation inhibiting S-[15N]nitroso compounds

    International Nuclear Information System (INIS)

    [15N]Nitric oxide (15NO) was produced in a ''gastight'' flask from [15N]nitrite by reaction with iodide in acetic acid acidified water and purged for 60 min by a continuous nitrogen gas stream applied through an uncoated polytetrafluoroethylene flate membrane into a second flask which contained a methanolic solution of N-acetyl-L-cysteine or N-acetyl-DL-penicillamine. Analysis of these solutions by UV spectroscopy, reversed-phase high-performance liquid chromatography and capillary isotachophoresis showed formation of the corresponding S-nitroso compounds. Gas chromatographic-mass spectrometric analysis for [15N]nitrite which was formed by dissolving these compounds in aqueous buffered solutions gave an isotopic purity higher than 95% at 15N. The S-nitroso compounds were shown to inhibit ADP-induced platelet aggregation. (author)

  19. Alterations in aggregation function of whole blood platelets following irradiation

    International Nuclear Information System (INIS)

    By using whole blood platelet aggregometer, changes of platelet aggregation function following γ-irradiation with 6 Gy were studied. The results indicated that the function of platelet aggreation was enhanced from 4 hour to the third day after radiation, the peak value being on the third day. But it reduced on the seventh and tenth days. The early elevation of platelet aggregation may aggravate the microcirculation disturbances, while the reduction of platelet aggregation is one of the causes of hemorrhage syndrome following radiation. Therefore, measures effective in early inhibition and late improvement of platelet aggregation function may be helpful in repair of acute radiation injury

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    OpenAIRE

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

    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 (H2O), Amomyrtus l...

  2. The effect of ticlopidine administration to humans on the binding of adenosine diphosphate to blood platelets

    OpenAIRE

    Lips, J.P.M.; Sixma, J.J.; Schiphorst, M.E.

    1980-01-01

    Administration of Ticlopidine to human volunteers resulted in a prolonged bleeding time and decreased or absent aggregation of platelets with collagen and epinephrine. Adenosine diphosphate (ADP) induced platelet aggregation was initiated by a normal shape change, but the rate of the first wave of aggregation had decreased. The second wave of aggregation was absent. ADP-binding to platelets of volunteers, consisted of two classes of binding sites:one with high affinity and one with low affini...

  3. Clinical isolates of Enterococcus faecalis aggregate human platelets.

    OpenAIRE

    Rasmussen, Magnus; Johansson, Daniel; Karlsson Söbirk, Sara; Mörgelin, Matthias; Shannon, Oonagh

    2010-01-01

    Many endocarditis pathogens activate human platelets and this has been proposed to contribute to virulence. Here we report for the first time that many clinical isolates of Enterococcus faecalis, a common pathogen in infective endocarditis, aggregate human platelets. 84 isolates from human blood and urine were screened for their ability to aggregate platelets from four different donors. Platelet aggregation occurred for between 11 and 65 % of isolates depending on the donor. In one donor, a s...

  4. Gender differences in platelet aggregation in healthy individuals.

    Science.gov (United States)

    Otahbachi, Mohammad; Simoni, Jan; Simoni, Grace; Moeller, John F; Cevik, Cihan; Meyerrose, Gary E; Roongsritong, Chanwit

    2010-08-01

    This study evaluated gender variability in platelet aggregation in response to common agonists. Platelet aggregation was measured in 36 healthy men and women free of any antiplatelet medication, aged 22-36 years, of Caucasian (White not of Hispanic origin), Hispanic, and African-American not of Hispanic origin. In this ex-vivo study, we investigated platelet aggregation in response to adenosine-5'-diphosphate (ADP), epinephrine (EPI), arachidonic acid (AA) and collagen (COL), using a platelet ionized calcium aggregometer (Chrono-Log Co.). Platelet aggregation response to all tested agonists was higher in females than in males regardless of ethnicity. The most significant differences were observed with collagen (P < 0.01). Among the ethnic groups, Caucasian women were most prone to platelet aggregation. Gender is a determinant of agonist effects on platelet aggregability in healthy subjects. PMID:20039102

  5. Patterns of platelet aggregation in menstrual migraine.

    Science.gov (United States)

    Allais, G; Facco, G; Ciochetto, D; De Lorenzo, C; Fiore, M; Benedetto, C

    1997-12-01

    We investigated the threshold of the platelet release reaction during the luteal phase of the cycle in 46 patients suffering from menstrual migraine (MM) and 27 healthy normal women. The distribution in both groups of the three types of aggregometric curves (types 1, 2 or 3) obtained in response to ADP 1 microM as aggregating agent was evaluated. Among MM sufferers, 19 (41%) showed a type 1 curve, while 14 (31%) had a type 2 curve and 13 (28%) showed an irreversible aggregation with a type 3 pattern. Curve distribution in controls was 18 (67%) for type 1, 8 (30%) for type 2 and 1 (3%) for type 3. A significantly (p < 0.05) different distribution of the three curve types between MM and controls was present, suggesting that a secondary wave of aggregation is more frequent in MM; the highest difference was due to the observed frequencies of type 3 curves. PMID:9496778

  6. N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin.

    OpenAIRE

    Loscalzo, J

    1985-01-01

    Platelet aggregation is currently felt to play an important role in the pathogenesis of ischemic vascular disorders. The smooth muscle relaxant, nitroglycerin, has been shown to inhibit platelet aggregation in vitro, but at concentrations that were felt to be unattainable in vivo. Because the in vivo action of nitroglycerin on smooth muscle cells has been shown to depend on the presence of reduced cytosolic sulfhydryl groups, the inhibitory effect of nitroglycerin on platelet aggregation was ...

  7. Inhibition of platelet aggregation by vanilloid-like agents is not mediated by transient receptor potential vanilloid-1 channels or cannabinoid receptors.

    Science.gov (United States)

    Almaghrabi, Safa; Geraghty, Dominic; Ahuja, Kiran; Adams, Murray

    2016-06-01

    Vanilloid-like agents, including capsaicin, N-arachidonoyl-dopamine and N-oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid-1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)-induced aggregation. This research is extended to investigate the effect of these vanilloid-like-agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid. Incubation of platelets with each of the individual vanilloids, or with receptor antagonists of TRPV1 (SB452533), CB1 (AM251) and CB2 (AM630), for up to 2 h did not significantly affect the platelet count. Similarly, the effect of individual vanilloids on the inhibition of platelet aggregation was not significantly different in the presence of receptor agonists compared to control, irrespective of the agonist used, suggesting that the inhibitory effect of vanilloids on platelet aggregation is independent of TRPV1, CB1 and CB2 receptors. Further research on the antiplatelet activity of vanilloids should focus on mechanisms other than those associated with vanilloid receptors. PMID:26991025

  8. Inhibition of platelet aggregation by transdermal glyceryl trinitrate.

    OpenAIRE

    R. Andrews; May, J. A.; Vickers, J.; Heptinstall, S

    1994-01-01

    OBJECTIVE--To determine the optimum conditions for the demonstration of an antiplatelet effect of nitric oxide and to use these conditions to elucidate the effects of a transdermal glyceryl trinitrate patch on platelet aggregation in normal volunteers. METHODS--An open prospective crossover study. The effects of nitric oxide on platelet aggregation in whole blood and platelet rich plasma as stimulated by adenosine diphosphate and U46619 was assessed in the presence and absence of iloprost and...

  9. Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment

    OpenAIRE

    Erlinge David; Högberg Carl; Braun Oscar Ö

    2009-01-01

    Abstract Background Mild hypothermia is currently standard of care for cardiac arrest patients in many hospitals and a common belief is that hypothermia attenuates platelet aggregation. We wanted to examine the effects of clopidogrel on platelet aggregation during hypothermia. Methods Platelet reactivity at 37°C and 33°C was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein (VASP) in blood from healthy volunteers before, and 24 hours after, a 600 mg loadin...

  10. Suppression of Platelet Aggregation by Bordetella pertussis Adenylate Cyclase Toxin

    OpenAIRE

    Iwaki, Masaaki; Kamachi, Kazunari; Heveker, Nikolaus; Konda, Toshifumi

    1999-01-01

    The effect of Bordetella pertussis adenylate cyclase toxin (ACT) on platelet aggregation was investigated. This cell-invasive adenylate cyclase completely suppressed ADP (10 μM)-induced aggregation of rabbit platelets at 3 μg/ml and strongly suppressed thrombin (0.2 U/ml)-induced aggregation at 10 μg/ml. The suppression was accompanied by marked increase in platelet intracellular cyclic AMP (cAMP) content and was diminished by the anti-ACT monoclonal antibody B7E11. A catalytically inactive p...

  11. Platelet aggregation in rats at a period of postirradiation repair

    International Nuclear Information System (INIS)

    Platelet aggregation in rats was investigated after total gamma-irradiation with a dose of 2 Gr. At period postirradiation repair the phase character of changes of some aggregation parameters was discovered. After 2-6 months the main direction of age changes of aggregation time was lesser then in control groop

  12. Lonomia obliqua venomous secretion induces human platelet adhesion and aggregation.

    Science.gov (United States)

    Berger, Markus; Reck, José; Terra, Renata M S; Beys da Silva, Walter O; Santi, Lucélia; Pinto, Antônio F M; Vainstein, Marilene H; Termignoni, Carlos; Guimarães, Jorge A

    2010-10-01

    The caterpillar Lonomia obliqua is a venomous animal that causes numerous accidents, especially in southern Brazil, where it is considered a public health problem. The clinical manifestations include several haemostatic disturbances that lead to a hemorrhagic syndrome. Considering that platelets play a central role in hemostasis, in this work we investigate the effects of L. obliqua venomous secretion upon blood platelets responses in vitro. Results obtained shows that L. obliqua venom directly induces aggregation and ATP secretion in human washed platelets in a dose-dependent manner. Electron microscopy studies clearly showed that the venomous bristle extract was also able to produce direct platelets shape change and adhesion as well as activation and formation of platelet aggregates. Differently from other enzyme inhibitors, the venom-induced platelet aggregation was significatively inhibited by p-bromophenacyl bromide, a specific inhibitor of phospholipases A2. Additional experiments with different pharmacological antagonists indicate that the aggregation response triggered by the venom active components occurs through a calcium-dependent mechanism involving arachidonic acid metabolite(s) of the cyclooxygenase pathway and activation of phosphodiesterase 3A, an enzyme that leads to the consumption of intracellular cAMP content. It was additionally found that L. obliqua-induced platelet aggregation was independent of ADP release. Altogether, these findings are in line with the need for a better understanding of the complex hemorrhagic syndrome resulting from the envenomation caused by L. obliqua caterpillars, and can also give new insights into the management of its clinical profile. PMID:20157842

  13. Aluminum induces lipid peroxidation and aggregation of human blood platelets

    Directory of Open Access Journals (Sweden)

    Neiva T.J.C.

    1997-01-01

    Full Text Available Aluminum (Al3+ intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated that Al3+-induced blood platelet aggregation was mediated by lipid peroxidation. Using chemiluminescence (CL of luminol as an index of total lipid peroxidation capacity, we established a correlation between lipid peroxidation capacity and platelet aggregation. Al3+ (20-100 µM stimulated CL production by human blood platelets as well as their aggregation. Incubation of the platelets with the antioxidants nor-dihydroguaiaretic acid (NDGA (100 µM and n-propyl gallate (NPG (100 µM, inhibitors of the lipoxygenase pathway, completely prevented CL and platelet aggregation. Acetyl salicylic acid (ASA (100 µM, an inhibitor of the cyclooxygenase pathway, was a weaker inhibitor of both events. These findings suggest that Al3+ stimulates lipid peroxidation and the lipoxygenase pathway in human blood platelets thereby causing their aggregation

  14. The automation of routine light transmission platelet aggregation

    OpenAIRE

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

    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). Pl...

  15. In vitro model of platelet aggregation in stenotic arteries

    International Nuclear Information System (INIS)

    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

  16. Horse chestnut extract contracts bovine vessels and affects human platelet aggregation through 5-HT(2A) receptors: an in vitro study.

    Science.gov (United States)

    Felixsson, Emma; Persson, Ingrid A-L; Eriksson, Andreas C; Persson, Karin

    2010-09-01

    Extract from seeds and bark of horse chestnut (Aesculus hippocastanum L) is used as an herbal medicine against chronic venous insufficiency. The effect and mechanism of action on veins, arteries, and platelets are not fully understood. The aim of this study was to investigate the effects and mechanisms of action of horse chestnut on the contraction of bovine mesenteric veins and arteries, and human platelet aggregation. Contraction studies showed that horse chestnut extract dose-dependently contracted both veins and arteries, with the veins being the most sensitive. Contraction of both veins and arteries were significantly inhibited by the 5-HT(2A) receptor antagonist ketanserin. No effect on contraction was seen with the cyclooxygenase inhibitor indomethacin, the alpha(1) receptor antagonist prazosin or the angiotensin AT(1) receptor antagonist saralasin neither in veins nor arteries. ADP-induced human platelet aggregation was significantly reduced by horse chestnut. A further reduction was seen with the extract in the presence of ketanserin. In conclusion, horse chestnut contraction of both veins and arteries is, at least partly, mediated through 5-HT(2A) receptors. Human platelet aggregation is reduced by horse chestnut. The clinical importance of these findings concerning clinical use, possible adverse effects, and drug interactions remains to be investigated. PMID:20148408

  17. 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 and...... < 0.0003), except RISTOlow (p = 0.05). A reference interval is presented as 95% confidence interval suitable for any age and both sex. Day-to-day variation was < 11% for all agonists except for RISTOlow. No association was found between platelet aggregation and haematocrit or red blood cell count...

  18. Pistacia chinensis Methanolic Extract Attenuated MAPK and Akt Phosphorylations in ADP Stimulated Rat Platelets In Vitro

    Directory of Open Access Journals (Sweden)

    Ji Young Park

    2012-01-01

    (2.5–20 μg/mL inhibited ADP-induced platelet aggregation. While PCME diminished [Ca2+]i, ATP, and TXA2 release in ADP-activated platelets, it enhanced cAMP production in resting platelets. Likewise, PCME inhibited fibrinogen binding to αIIbβ3 and downregulated JNK, ERK, and Akt phosphorylations. Thus, PCME contains potential antiplatelet compounds that could be deployed for their therapeutic values in cardiovascular pathology.

  19. The effect of time of day and exercise on platelet functions and platelet-neutrophil aggregates in healthy male subjects.

    Science.gov (United States)

    Aldemir, Hatice; Kiliç, Nedret

    2005-12-01

    Platelet activation state changes by exercise. The effect of exercise time on platelet activation state and formation of platelet-neutrophil aggregates are not known yet. In this study the effect of exercise and time of day were examined on platelet activity with platelet-neutrophil aggregates. Ten moderately active males aged 27+/- 1.63 (mean+/-S.D.) years completed sub-maximal (70% VO(2max)) exercise trials for 30 min. Blood pressure (BP) was recorded. Venous blood samples were obtained at rest, immediately post-exercise and after 30 min of recovery. Whole blood was analysed for haematocrit (Hct), haemoglobin (Hb), platelet count (PC), mean platelet count (MPV) and platelet aggregation (PA). Platelet-neutrophil aggregates and beta-thromboglobulin (beta-TG) levels were assayed. Platelet count showed significant increase after morning exercise ((236+/- 32)x10(9) l(-1) versus (202+/- 34)x10(9) l(-1) baseline, p 11912

  20. 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.

  1. [Isosorbide dinitrate inhibits in vitro platelet aggregation at submicromolar concentrations].

    Science.gov (United States)

    Gachet, C; Guillou, J; Moog, S; Cazenave, J P

    1992-04-01

    Nitrate derivatives have in vivo and in vitro platelet anti-aggregant properties in addition to their vasodilatory effects. The mode of action is related to increased intracytoplasmic cyclic GMP concentrations. It has been shown that isosorbide dinitrate (ISDN) has this type of platelet anti-aggregant activity but the reported results about the active concentrations and the inhibited pathways of activation are contradictory. This study was designed to determine whether ISDN has in vitro platelet anti-aggregant activity at low doses and to verify if this effect is selective by aggregation induced by ADP. Finally, a possible potentialisation of the inhibitors due to ISDN was looked for with cyclic nucleotide phosphodiesterase inhibitors and with agents simulating the effect of adenylate cyclase. The results showed that: 1) ISDN had platelet anti-aggregant activity in vitro at concentrations of about 10-7 M, 2) that this effect was not limited to the aggregation induced by ADP as the aggregation induced by PAF-acether was also inhibited by low dose ISDN, 3) of the cyclic nucleotide modulators tested, only quercetine (flavonoide) potentialised the effects of ISDN. PMID:1326933

  2. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation

    OpenAIRE

    Jang, Ja-Young; Kim, Tae-Su; Cai, Jingmei; Kim, Jihyun; Kim, Youngeun; Shin, Kyungha; Kim, Kwang Sei; Park, Sung Kyeong; Lee, Sung-Pyo; Choi, Ehn-Kyoung; Rhee, Man Hee; Kim, Yun-Bae

    2013-01-01

    The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-depende...

  3. Influence of caffeine on blood pressure and platelet aggregation

    OpenAIRE

    2000-01-01

    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, par...

  4. 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...... the methodology 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....

  5. 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.

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

    OpenAIRE

    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 single platelet disappearance and secretion were hardly affected. Prelowering the platelet energy content, while preserving the adenylate energy charge, made both optical aggregation and the secretion...

  7. Disabled-2 regulates platelet heterotypic and homotypic aggregation through sulfatide binding

    OpenAIRE

    Welsh, John Douglas

    2010-01-01

    At the site of vascular injury platelet aggregation serves to stem blood flow, initiate the inflammatory response, and stimulate wound healing. Platelets become stimulated, release their granule contents, and become adherent to one another. Platelet granules contain important clotting factors and regulators of aggregation. Disabled-2 (Dab2) is a negative regulator of platelet aggregation released from platelet α-granules. Dab2 binds to the αIIbβ3 integrin, through the PTB domain, and b...

  8. Modifications of platelet aggregation during treadmill section and obstacle course in athletic horse

    OpenAIRE

    Piccione G.; Assenza Anna; Casella Stefania; Giannetto Claudia; Tosto F.; Caola G.

    2010-01-01

    Eight clinically healthy Sella Italiana horses were used in order to assess the variations of platelet aggregation in response to different workload. Blood samples were collected from each horse at rest, immediately after exercise and 30 min after the end of the exercise. By means of an aggregometer platelet aggregation was quantitated as maximum degree of platelet aggregation and initial velocity platelet aggregation. Two-way repeated measures analysis of variance (ANOVA) was applied to dete...

  9. Dose response of surfactants to attenuate gas embolism related platelet aggregation

    Science.gov (United States)

    Eckmann, David M.; Eckmann, Yonaton Y.; Tomczyk, Nancy

    2014-03-01

    Intravascular gas embolism promotes blood clot formation, cellular activation, and adhesion events, particularly with platelets. Populating the interface with surfactants is a chemical-based intervention to reduce injury from gas embolism. We studied platelet activation and platelet aggregation, prominent adverse responses to blood contact with bubbles. We examined dose-response relationships for two chemically distinct surfactants to attenuate the rise in platelet function stimulated by exposure to microbubbles. Significant reduction in platelet aggregation and platelet activation occurred with increasing concentration of the surfactants, indicating presence of a saturable system. A population balance model for platelet aggregation in the presence of embolism bubbles and surfactants was developed. Monte Carlo simulations for platelet aggregation were performed. Results agree qualitatively with experimental findings. Surfactant dose-dependent reductions in platelet activation and aggregation indicate inhibition of the gas/liquid interface's ability to stimulate cellular activation mechanically.

  10. Scalable evaluation of platelet aggregation by the degree of blood migration

    Science.gov (United States)

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

    2013-12-01

    Platelet aggregation plays a key role in vascular thrombosis. Antiplatelet drug therapy is commonly used for the prevention of abnormal platelet aggregation. So, measuring platelet aggregation function is critically important in clinical field. Here, we introduce a scalable evaluation method of platelet aggregation measured with the degree of blood migration through microchannel in a microfluidic chip. Unlike conventional methods that require expertise with system physics to operate devices, our approach is using microfluidics system, which requires only a syringe vacuum. The scalable migration factors, migration distance and touchdown time, are capable of distinguishing various antiplatelet drug effects under microfluidics and would be effective for the quick and easy evaluation of quantitative platelet aggregation.

  11. Antipsychotic Drugs Inhibit Platelet Aggregation via P2Y 1 and P2Y 12 Receptors

    OpenAIRE

    Chang-Chieh Wu; Fu-Ming Tsai; Mao-Liang Chen; Semon Wu; Ming-Cheng Lee; Tzung-Chieh Tsai; Lu-Kai Wang; Chun-Hua Wang

    2016-01-01

    Antipsychotic drugs (APDs) used to treat clinical psychotic syndromes cause a variety of blood dyscrasias. APDs suppress the aggregation of platelets; however, the underlying mechanism remains unknown. We first analyzed platelet aggregation and clot formation in platelets treated with APDs, risperidone, clozapine, or haloperidol, using an aggregometer and rotational thromboelastometry (ROTEM). Our data indicated that platelet aggregation was inhibited, that clot formation time was increased, ...

  12. Pistacia chinensis Methanolic Extract Attenuated MAPK and Akt Phosphorylations in ADP Stimulated Rat Platelets In Vitro

    OpenAIRE

    Ji Young Park; Mei Hong; Qi Jia; Young-Chul Lee; Taddesse Yayeh; Eujin Hyun; Dong-Mi Kwak; Jae Youl Cho; Man Hee Rhee

    2012-01-01

    Pistacia chinensis (Chinese pistache) is a widely grown plant in southern China where the galls extract is a common practice in folk medicine. However, extracts from this plant have never been attempted for their cardiovascular protective effects in experimental setting. Here therefore we aimed to investigate the antiplatelet activity of Pistacia chinensis methanolic extract (PCME) in ADP stimulated rat platelets in vitro. PCME (2.5–20 μg/mL) inhibited ADP-induced platelet aggregation. While ...

  13. 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

  14. Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with normal saline in a large animal model of multisystem trauma

    DEFF Research Database (Denmark)

    Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S; Jin, Guang; Jepsen, Cecilie H; Imam, Ayesha; Hwabejire, John O; Deperalta, Danielle; Duggan, Michael; DeMoya, Marc; Velmahos, George C; Alam, Hasan B

    2014-01-01

    multisystem trauma (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with hemorrhagic shock (40% of estimated blood volume). Animals were left in shock (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with three times shed volume NS (n = 6) or one times...... volume FFP (n = 6) and monitored for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)-induced platelet aggregation at baseline, after 2 hours of shock following resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of platelet activation (transforming growth...... factor β [TGF-β], sP-Selectin, and CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) were also assayed. Thromboelastography was used to measure clotting activity. RESULTS: ADP-induced platelet aggregation was significantly higher...

  15. 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.

  16. Platelets aggregation in pathological conditions: role of local shear rates and platelet activation delay time.

    Science.gov (United States)

    Li, He; Zarif Khalili Yazdani, Alireza; Karniadakis, George

    2015-11-01

    Platelets play an essential role in the initiation and formation of a thrombus, however their detailed motion in blood vessels with complex geometries, such as in the aneurysmal vessel or stenotic vessel in atherosclerosis, has not been studied systematically. Here, we perform spectral element simulations (NEKTAR code) to obtain the 3D flow field in blood vessel with cavities, and we apply the force coupling method (FCM) to simulate the motion of platelets in blood flow. Specifically, simulations of platelets are performed in a 0.25 mm diameter circular blood vessel with 1 mm length. Corresponding coarse-grained molecular dynamics simulations are employed to provide input to the NEKTAR-FCM code. Simulations are conducted at several different Reynolds numbers (Re). An ellipsoid-shaped cavity is selected to intersect with the middle part of the circular vessel to represent the aneurysmal part of the blood vessel. Based on the simulation results, we quantify how the platelets motion and aggregation in the blood vessel cavities depend on Re, platelet activation delay time, and the geometry of the cavities.

  17. Triggering by Paf-acether and adrenaline of cyclo-oxygenase-independent platelet aggregation.

    OpenAIRE

    Fouque, F.; Vargaftig, B B

    1984-01-01

    Platelet-activating factor (Paf-acether, 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) induced full aggregation and a limited release reaction of human platelets in plasma or in blood. Cyclo-oxygenase inhibition with aspirin only reduced aggregation when induced by threshold amounts of Paf-acether, whereas higher concentrations surmounted inhibition whether tested in citrated or in heparinized platelet-rich plasma or blood. Aspirin-induced inhibition of platelet secretion by Paf-acether wa...

  18. Involvement of Nitric Oxide on Calcium Mobilization and Arachidonic Acid Pathway Activation during Platelet Aggregation with different aggregating agonists

    OpenAIRE

    Banerjee, Debipriya; Mazumder, Sahana; Kumar Sinha, Asru

    2016-01-01

    Platelet aggregation by different aggregating agonists is essential in the normal blood coagulation process, the excess of which caused acute coronary syndrome (ACS). In all cases, the activation of arachidonic acid by cycloxygenase was needed for the synthesis of thromboxane A2 (TXA2) but the mechanism of arachidonic acid release in platelets remains obscure. Studies were conducted to determine the role of nitric oxide (NO), if any, on the release of arachidonic acid in platelets. The cytoso...

  19. Whole Blood Platelet Aggregation and Release Reaction Testing in Uremic Patients

    OpenAIRE

    Louis DePalma; Lew, Susie Q.; Jason Schallheim; Jay Zeck

    2013-01-01

    Background. Platelet function analysis utilizing platelet-rich plasma and optical density based aggregometry fails to identify patients at risk for uremia associated complications. Methods. We employed whole blood platelet aggregation analysis based on impedance as well as determination of ATP release from platelet granules detected by a chemiluminescence method. Ten chronic kidney disease (CKD) stage 4 or 5 predialysis patients underwent platelet evaluation. Our study aims to evaluate this p...

  20. Keishibukuryogan, a Traditional Japanese Medicine, Inhibits Platelet Aggregation in Guinea Pig Whole Blood

    OpenAIRE

    Kiyoshi Terawaki; Masamichi Noguchi; Mitsutoshi Yuzurihara; Yuji Omiya; Yasushi Ikarashi; Yoshio Kase

    2015-01-01

    Effects of keishibukuryogan (KBG) on platelet aggregation were investigated. To ensure the specificity of KBG, tokishakuyakusan (TSS) and kamisyoyosan (KSS), which are known to have platelet aggregation-inhibiting effects, and rikkunshito (RKT) and shakuyakukanzoto (SKT), which are considered to be devoid of such effects, were used for comparison. The platelet aggregation of each test drug was measured by the screen filtration pressure method using whole blood of guinea pigs and expressed as ...

  1. The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress.

    OpenAIRE

    Y. Ikeda; Handa, M; Kawano, K; Kamata, T; Murata, M.; Araki, Y; Anbo, H; Kawai, Y; Watanabe, K.; Itagaki, I

    1991-01-01

    Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]o), platelet aggregation can be induced under low...

  2. Selective PKCalpha inhibition uncouples platelet angiogenesis promotion from collagen-induced aggregation

    OpenAIRE

    Radomski, Marek

    2013-01-01

    Platelets promote angiogenesis by releasing angiogenesis-regulating factors from their α-granules upon aggregation. This effect has both physiologic and pathologic significance as it may contribute to carcinogenesis. Platelet α-granule release and aggregation are regulated, in part, via protein kinase C (PKC) α and β signaling. Our study investigated the effects of PKC inhibition on aggregation, angiogenesis-regulator secretion from α-granules, and platelet-stimulated angiogenesis. We hypothe...

  3. Impact of the bioresorbable vascular scaffold surface area on on-treatment platelet reactivity.

    Science.gov (United States)

    Gross, Lisa; Sibbing, Dirk; Eickhoff, Madeleine; Baquet, Moritz; Orban, Martin; Krieg, Anne; Grujic, Katarina; Theiss, Hans D; Brunner, Stefan; Teupser, Daniel; Holdt, Lesca; Massberg, Steffen; Mehilli, Julinda

    2016-07-01

    While promising data with the novel bioresorbable vascular scaffold (BVS) are accumulating, signals of scaffold thrombosis (ST) were noted in recent reports. We aimed to assess the relationship between the total surface area (TSA) of implanted everolimus-eluting BVSs and the on-treatment adenosine diphosphate (ADP)-induced platelet reactivity in patients undergoing percutaneous coronary intervention (PCI). 202 consecutive patients undergoing BVS implantation and platelet function testing were included. For investigating the impact of the scaffold surface on platelet reactivity, patients were stratified into two groups regarding the median BVS TSA. The on-treatment ADP-induced platelet reactivity was determined with the Multiplate analyzer and 30-day follow-up was available in 98% of patients. ADP-induced platelet aggregation values (median, [IQR]) did not differ between the two study groups (12.0 [9.0-19.0] U for patients with TSA > 1.39 cm(2) and 13.0 [9.0-19.5] U for patients with TSA ≤ 1.39 cm(2); p = 0.69). No correlation was observed between the BVS TSA and levels of platelet reactivity (Spearman rank correlation = -0.10, p = 0.16). At 30 days after PCI, two early STs (1%) were documented. Thus, in patients on a dual antiplatelet treatment regimen following BVS implantation, the extent of blood-to-BVS contact surface does not negatively affect levels of on-treatment platelet reactivity. PMID:26940818

  4. Rapid in vitro biocompatibility assay of endovascular stents by flow cytometry using platelet activation and platelet-leukocyte aggregation.

    Science.gov (United States)

    Tárnok, A; Mahnke, A; Müller, M; Zotz, R J

    1999-02-15

    Clinical studies suggest that stent design and surface texture are responsible for differences in biocompatibility of metallic endovascular stents. A simple in vitro experimental setup was established to test stent-induced degree of platelet and leukocyte activation and platelet-leukocyte aggregation by flow cytometry. Heparin-coated tantalum stents and gold-coated and uncoated stainless steel stents were tested. Stents were implanted into silicone tubes and exposed to blood from healthy volunteers. Platelet and leukocyte activation and percentage of leukocyte-platelet aggregates were determined in a whole-blood assay by subsequent staining for activation-associated antigens (CD41a, CD42b, CD62p, and fibrinogen binding) and leukocyte antigens (CD14 and CD45) and flow cytometric analysis. Blood taken directly after venous puncture or exposed to the silicone tube alone was used as negative controls. Positive control was in vitro stimulation with thrombin receptor activating peptide (TRAP-6). Low degree of platelet activation and significant increase in monocyte- and neutrophil-platelet aggregation were observed in blood exposed to stents (P coated stents continuously induced less platelet activation and leukocyte-platelet aggregation than uncoated stainless steel stents of the same length and shorter stents of the same structure. Stent surface coating and texture plays a role in platelet and leukocyte activation and leukocyte-platelet aggregation. Using this simple in vitro assay and whole blood and flow cytometry, it seems possible to differentiate stents by their potency to activate platelets and/or leukocytes. This assay could be applied for improving the biocompatibility of coronary stents. PMID:10088974

  5. Production and characterization of monoclonal antibodies against rat platelet GPIIb/IIIa

    International Nuclear Information System (INIS)

    Four murine monoclonal antibodies against rat platelets were produced by fusion of spleen cells from mice intravenously immunized with whole rat platelets. All four antibodies immunoprecipitated two major platelet membrane proteins with apparent molecular weights of 130,000 and 82,000 (nonreduced) and of 120,000 and 98,000 (reduced), which were structurally analogous to human glycoprotein (GP) IIb/IIIa, i.e. rat GPIIb/IIIa. Two of four antibodies, named P9 and P55, strongly inhibited adenosine diphosphate (ADP)-induced aggregation of washed rat platelets and caused approximately 50% inhibition of human fibrinogen binding to ADP-stimulated rat platelets, suggesting that rat GPIIb/IIIa serves as a fibrinogen receptor in ADP-induced aggregation. In contrast, two other antibodies, named P14 and P34, themselves caused aggregation of rat platelets in platelet-rich plasma (PRP) and the secretion of 14C-serotonin from 14C-serotonin-labeled PRP. These results indicate that rat GPIIb/IIIa plays an important role in platelet aggregation

  6. Involvement of Nitric Oxide on Calcium Mobilization and Arachidonic Acid Pathway Activation during Platelet Aggregation with different aggregating agonists.

    Science.gov (United States)

    Banerjee, Debipriya; Mazumder, Sahana; Kumar Sinha, Asru

    2016-03-01

    Platelet aggregation by different aggregating agonists is essential in the normal blood coagulation process, the excess of which caused acute coronary syndrome (ACS). In all cases, the activation of arachidonic acid by cycloxygenase was needed for the synthesis of thromboxane A2 (TXA2) but the mechanism of arachidonic acid release in platelets remains obscure. Studies were conducted to determine the role of nitric oxide (NO), if any, on the release of arachidonic acid in platelets. The cytosolic Ca(2+) was visualized and quantitated by fluorescent spectroscopy by using QUIN-2. NO was measured by methemoglobin method. Arachidonic acid was determined by HPLC. TXA2 was measured as ThromboxaneB2 (TXB2) by ELISA. Treatment of platelets in platelet-rich plasma (PRP) with different aggregating agents resulted in the inhibition of nitric oxide synthase (NOS) which inhibited the production of NO synthesis and increased TXA2 synthesis. Furthermore, the treatment of washed PRP with different platelet aggregating agents resulted in the increase of [Ca(2+)] in nM ranges. In contrast, the pre-treatment of washed PRP with aspirin increased platelet NO level and inhibited the Ca(2+) mobilization and TXA2 synthesis. These results indicated that the aggregation of platelets by different aggregating agonists was caused by the cytosolic Ca(2+) mobilization due to the inhibition of NOS. PMID:27127451

  7. Selective inhibition of PAF-induced human platelet aggregation by garlic

    International Nuclear Information System (INIS)

    Garlic exudate (0.2-2.5 mg) prepared by squeezing fresh garlic cloves inhibited platelet aggregation induced by platelet activating factor (PAF) in a dose-dependent manner. No inhibition of aggregation was observed when adenosine-5-diphosphate (ADP) or arachidonic acid (AA) were used as aggregating agents. This selective effect of garlic against PAF-induced aggregation was also seen with aqueous or alcoholic garlic extracts. These results suggest that PAF antagonists are present in garlic. (author)

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

    Directory of Open Access Journals (Sweden)

    Corbalan JJ

    2012-02-01

    Full Text Available J Jose Corbalan1,2, Carlos Medina1, Adam Jacoby2, Tadeusz Malinski2, Marek W Radomski11School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences, Panoz Institute, Trinity College Dublin, Ireland; 2Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USABackground: 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.Keywords: amorphous silica nanoparticles, nanotoxicology, nitric oxide, peroxynitrite, platelet aggregation

  9. Platelet Aggregation Study in Patients With Hemoglobin Eβ Thalassemia in India.

    Science.gov (United States)

    Ghosal, Tanushree; Dolai, Tuphan Kanti; Mandal, Prakas Kumar; Karthik, S; Bandyopadhyay, Anjali

    2016-09-01

    Hemoglobin Eβ thalassemia is a major public health problem in India, especially in the state of West Bengal. Various thromboembolic events are common, especially in splenectomized patients. Platelet hyperactivity most likely plays a pathogenetic role. To investigate the role of platelets in hypercoagulability, platelet aggregation tests were undertaken in the present study. Platelet-rich plasma from 30 patients with Eβ thalassemia (15 splenectomized and 15 nonsplenectomized) were studied and compared with 15 healthy participants. The 4 agonists used were adenosine 5-diphosphate, adrenaline (epinephrine), collagen, and ristocetin. The current study shows both splenectomized and nonsplenectomized patients had abnormal aggregation compared to normal healthy controls. Splenectomized patients had higher platelet aggregation than nonsplenectomized patients for all 4 agonists; but statistically significant difference among 2 groups was found only for collagen. The present study confirms a role of splenic absence in platelet hyperaggregation. PMID:25701765

  10. Whole Blood Platelet Aggregation and Release Reaction Testing in Uremic Patients

    Directory of Open Access Journals (Sweden)

    Jay Zeck

    2013-01-01

    Full Text Available Background. Platelet function analysis utilizing platelet-rich plasma and optical density based aggregometry fails to identify patients at risk for uremia associated complications. Methods. We employed whole blood platelet aggregation analysis based on impedance as well as determination of ATP release from platelet granules detected by a chemiluminescence method. Ten chronic kidney disease (CKD stage 4 or 5 predialysis patients underwent platelet evaluation. Our study aims to evaluate this platform in this patient population to determine if abnormalities could be detected. Results. Analysis revealed normal aggregation and ATP release to collagen, ADP, and high-dose ristocetin. ATP release had a low response to arachidonic acid (0.37 ± 0.26 nmoles, reference range: 0.6–1.4 nmoles. Platelet aggregation to low-dose ristocetin revealed an exaggerated response (20.9 ± 18.7 ohms, reference range: 0–5 ohms. Conclusions. Whole blood platelet analysis detected platelet dysfunction which may be associated with bleeding and thrombotic risks in uremia. Diminished ATP release to arachidonic acid (an aspirin-like defect in uremic patients may result in platelet associated bleeding. An increased aggregation response to low-dose ristocetin (a type IIb von Willebrand disease-like defect is associated with thrombus formation. This platelet hyperreactivity may be associated with a thrombotic diathesis as seen in some uremic patients.

  11. Platelet impedance aggregation in whole blood and its inhibition by antiplatelet drugs.

    OpenAIRE

    Mackie, I J; Jones, R.; Machin, S. J.

    1984-01-01

    Platelet aggregation was studied in citrated whole blood by an electrical impedance method. Blood samples from normal volunteers were studied with the aim of finding a suitable method for the routine study of samples from patients. An erratic tracing and low maximum aggregation were seen in samples with a high normal haematocrit. Optimal aggregation was seen when blood was diluted to a haematocrit of .300; isotonic saline was a better diluent than platelet poor plasma. No appreciable differen...

  12. The influence on rabbit platelet aggregation following γ ray whole-body-irradiation with 400 rads

    International Nuclear Information System (INIS)

    In this paper, using the method of turbidmetric technique, changes of rabbit platelet aggregation are observed following γ ray whole-body irradiation with 400 rads. The results indicated that the function of blood platelet aggregation was risen from the first to the fifth day after irradiation, but reduced at the seventh day and markedly at the tenth. It is believed that the early elevation of platelet aggregation may result in increase of adherence and coagulation, and enhance microcirculation disturbances. In addition, a large number of platelets and coagulation factors were consumed, and it might be one of the causes of hemorrhage syndrome after exposure. Dueing early therapy of radiation injury, therefore, it is of benefit for improving the repair of radiation injury to inhibit platelet aggregation

  13. Physical and chemical effects of red cells in the shear-induced aggregation of human platelets.

    OpenAIRE

    Goldsmith, H L; Bell, D N; Braovac, S; Steinberg, A.; McIntosh, F

    1995-01-01

    Both chemical and physical effects of red cells have been implicated in the spontaneous aggregation of platelets in sheared whole blood (WB). To determine whether the chemical effect is due to ADP leaking from the red cells, a previously described technique for measuring the concentration and size of single platelets and aggregates was used to study the shear-induced aggregation of platelets in WB flowing through 1.19-mm-diameter polyethylene tubing in the presence and absence of the ADP scav...

  14. An atypical IgM class platelet cold agglutinin induces GPVI-dependent aggregation of human platelets.

    Science.gov (United States)

    Sánchez Guiu, I M; Martínez-Martinez, I; Martínez, C; Navarro-Fernandez, J; García-Candel, F; Ferrer-Marín, F; Vicente, V; Watson, S P; Andrews, R K; Gardiner, E E; Lozano, M L; Rivera, J

    2015-08-01

    Platelet cold agglutinins (PCA) cause pseudothrombocytopenia, spurious thrombocytopenia due to ex vivo platelet clumping, complicating clinical diagnosis, but mechanisms and consequences of PCA are not well defined. Here, we characterised an atypical immunoglobulin (Ig)M PCA in a 37-year-old woman with lifelong bleeding and chronic moderate thrombocytopenia, that induces activation and aggregation of autologous or allogeneic platelets via interaction with platelet glycoprotein (GP)VI. Patient temperature-dependent pseudothrombocytopenia was EDTA-independent, but was prevented by integrin αIIbβ3 blockade. Unstimulated patient platelets revealed elevated levels of bound IgM, increased expression of activation markers (P-selectin and CD63), low GPVI levels and abnormally high thromboxane (TX)A2 production. Patient serum induced temperature- and αIIbβ3-dependent decrease of platelet count in allogeneic donor citrated platelet-rich plasma (PRP), but not in PRP from Glanzmann's thrombasthenia or afibrinogenaemia patients. In allogeneic platelets, patient plasma induced shape change, P-selectin and CD63 expression, (14)C-serotonin release, and TXA2 production. Activation was not inhibited by aspirin, cangrelor or blocking anti-Fc receptor (FcγRIIA) antibody, but was abrogated by inhibitors of Src and Syk, and by a soluble GPVI-Fc fusion protein. GPVI-deficient platelets were not activated by patient plasma. These data provide the first evidence for an IgM PCA causing platelet activation/aggregation via GPVI. The PCA activity persisted over a five-year follow-up period, supporting a causative role in patient chronic thrombocytopenia and bleeding. PMID:25994029

  15. 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. PMID:25956790

  16. 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; Moesgaard, Sophia Gry; Rasmussen, Caroline Elisabeth; Kristensen, Annemarie Thuri; Falk, Bo Torkel

    2010-01-01

    binding),monocyte-platelet (MPAs) and neutrophil-platelet aggregates (NPAs) defined as leukocytes positive for CD61 were measured by whole blood flow cytometry asmarkers of platelet activation. For every dog platelet activation was assessed in unstimulated samples, and in response to exogenously added......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...... adenosine diphosphate (ADP), thrombin and a synthetic thromboxane A2 analogue 1 epinephrine. Complete blood count and biochemical screening were performed in all dogs. Dogs with CHF had higher MPAs (p 5 0.014) and NPAs ( p 5 0.021) compared to controls (2-way analysis of variance for repeated measurements)....

  17. An ethanol extract of Ramulus mori improves blood circulation by inhibiting platelet aggregation.

    Science.gov (United States)

    Lee, Jiyun; Kwon, Gayeung; Park, Jieun; Kim, Jeong-Keun; Choe, Soo Young; Seo, Yoonhee; Lim, Young-Hee

    2016-07-01

    Inappropriate platelet aggregation can cause blood coagulation and thrombosis. In this study, the effect of an ethanol extract of Ramulus mori (ERM) on blood circulation was investigated. The antithrombotic activity of ERM on rat carotid arterial thrombosis was evaluated in vivo, and the effect of ERM on platelet aggregation and blood coagulation time was evaluated ex vivo. To evaluate the safety of ERM, its cytotoxicity to platelets and its effect on tail bleeding time were assessed; ERM was not toxic to rat platelets and did not prolong bleeding time. Moreover, administering ERM to rats had a significant preventive effect on carotid arterial thrombosis in vivo, and significantly inhibited adenosine diphosphate- and collagen-induced platelet aggregation ex vivo, whereas it did not prolong coagulation periods, such as prothrombin time and activated partial thromboplastin time. The results suggest that ERM is effective in improving blood circulation via antiplatelet activity rather than anticoagulation activity. PMID:26967156

  18. Inhibitory Effects of Yuzu and Its Components on Human Platelet Aggregation

    OpenAIRE

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

    2015-01-01

    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 y...

  19. A serotonin-induced N-glycan switch regulates platelet aggregation.

    OpenAIRE

    Mercado, Charles P.; Quintero, Maritza V.; Yicong Li; Preeti Singh; Byrd, Alicia K.; Krajang Talabnin; Mayumi Ishihara; Parastoo Azadi; Rusch, Nancy J.; Balagurunathan Kuberan; Luc Maroteaux; Fusun Kilic

    2013-01-01

    Serotonin (5-HT) is a multifunctional signaling molecule that plays different roles in a concentration-dependent manner. We demonstrated that elevated levels of plasma 5-HT accelerate platelet aggregation resulting in a hypercoagulable state in which the platelet surface becomes occupied by several glycoproteins. Here we study the novel hypothesis that an elevated level of plasma 5-HT results in modification of the content of N-glycans on the platelet surface and this abnormality is associate...

  20. Intravascular filarial parasites inhibit platelet aggregation. Role of parasite-derived prostanoids.

    OpenAIRE

    L. X. Liu; Weller, P F

    1992-01-01

    The nematode parasites that cause human lymphatic filariasis survive for long periods in their vascular habitats despite continual exposure to host cells. Platelets do not adhere to blood-borne microfilariae, and thrombo-occlusive phenomena are not observed in patients with circulating microfilariae. We studied the ability of microfilariae to inhibit human platelet aggregation in vitro. Brugia malayi microfilariae incubated with human platelets caused dose-dependent inhibition of agonist-indu...

  1. 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 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. PMID:27273565

  2. The influence of organic peroxides on platelet aggregation and sensitivity to nitric oxide.

    Science.gov (United States)

    Naseem, K M; Bruckdorfer, K R

    1999-01-01

    The effects of oxidative stress, induced by water-soluble and lipid peroxides, on platelet reactivity and platelet sensitivity to nitric oxide were investigated. Hydrogen peroxide and cumene hydroperoxide potentiated thrombin-induced platelet aggregation. In contrast, 15(S)-hydroperoxyeicosatetraenoic acid had no such effect, while 12(S)-hydroperoxyeicosatetraenoic acid inhibited platelet reactivity. All of the peroxides tested were found to decrease platelet sensitivity to nitric oxide, although the mechanisms by which the various peroxides altered platelet sensitivity to nitric oxide were different. The water-soluble peroxides opposed the actions of nitric oxide without affecting cyclic GMP levels, while 15(S)-hydroperoxyeicosatetraenoic acid caused a significant reduction in the concentration of cyclic GMP formed in response to NO. The data from this study demonstrate that water-soluble and lipid peroxides both affect platelet reactivity and regulation, but by different mechanisms. Thus, caution should be exercised when selecting peroxides to be used as models of oxidative stress. PMID:16801085

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

    Directory of Open Access Journals (Sweden)

    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

  4. Better detection of platelet aggregation in patients with metabolic syndrome using epinephrine and ADP

    OpenAIRE

    Perez-Campos-Mayoral, Laura; Pérez-Campos,Eduardo; Zenteno, Edgar; Majluf-Cruz, Abraham; Perez-Ortega, Eduardo; Matias-Pérez, Diana; Rodal-Canales, Francisco J; Martínez-Cruz, Ruth; Pina-Canseco, Socorro; Reyes Franco, Miguel Angel; Mayoral Andrade, Gabriel; Hernández, Pedro; Gallegos, Belem

    2014-01-01

    Background Patients with metabolic syndrome (MS) often have increased platelet aggregation. In order to determine which concentration detects a higher level of platelet aggregation in patients with MS, the agonists ADP and epinephrine were compared. Methods The study included 56 subjects with MS and 53 healthy subjects. Blood pressure, weight, body-mass index, and hip-to-waist ratio were collected from all subjects. Insulin, glucose, total serum cholesterol, HDL-C, LDL-C, total triglycerides,...

  5. Increased platelet adhesion and aggregation in hypertensive patients: effect of atenolol.

    OpenAIRE

    Markel, A.; Brook, J. G.; LEVY, Y.; Aviram, M.; Youdim, M. B.

    1983-01-01

    Fourteen patients with established hypertension followed a double-blind crossover-styled trial to study the effects of 100 mg/day atenolol compared to placebo. Atenolol was found to be an effective antihypertensive agent, reducing both systolic and diastolic blood pressure. Hypertensive patients appear to have increased in vitro platelet adhesion and aggregation. Atenolol significantly reduced platelet adhesion, but had little effect on aggregation. This may be important in contributing towar...

  6. Greater Collagen-Induced Platelet Aggregation Following Cyclooxygenase 1 Inhibition Predicts Incident Acute Coronary Syndromes

    OpenAIRE

    Qayyum, Rehan; Becker, Diane M; Yanek, Lisa R.; Faraday, Nauder; Vaidya, Dhananjay; Mathias, Rasika; Kral, Brian G; Becker, Lewis C

    2014-01-01

    Greater ex vivo platelet aggregation to agonists may identify individuals at risk of acute coronary syndromes (ACS). However, increased aggregation to a specific agonist may be masked by inherent variability in other activation pathways. In this study, we inhibited the cyclooxygenase-1 (COX1) pathway with 2-week aspirin therapy and measured residual aggregation to collagen and ADP to determine whether increased aggregation in a non-COX1 pathway is associated with incident ACS. We assessed ex ...

  7. Early impact of prescription Omega-3 fatty acids on platelet biomarkers in patients with coronary artery disease and hypertriglyceridemia

    DEFF Research Database (Denmark)

    Serebruany, Victor L; Miller, Michael; Pokov, Alex N;

    2011-01-01

    Background: Prescription omega-3-acid ethyl esters (PO-3A) have been tested for outcome benefits in patients with coronary artery disease (CAD), arrhythmias and heart failure. Some evidence suggests that PO-3A may exert their benefit via inhibiting platelets. We tested the hypothesis that PO-3A may...... randomized 1:1:1 to Omacor™ 1 g/day (DHA/EPA ratio 1.25:1.0), Omacor 2 g/day, or a placebo for 2 weeks. Platelet tests including aggregometry and flow cytometry and cartridge analyzer readings were performed at baseline and at 1 and 2 weeks following PO-3A therapy. Results: ADP-induced platelet aggregation...

  8. Prolactin does not affect human platelet aggregation or secretion

    OpenAIRE

    Reuwer, A.Q.; Nieuwland, R.; Fernandez, I; Goffin, V.; Tiel, van, F.H.; 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 such hormones affect platelet function, is still controversial. It was the objective of this study to assess the ability of the pituitary hormone prolactin to affect platelet functions. Venous blo...

  9. Classification and possible mechanisms of action of some drugs that inhibit platelet aggregation

    International Nuclear Information System (INIS)

    Aggregating agents usually activate the 'basic platelet reaction' which induces the functions of shape change, aggregation, dense granule secretion and α-granule secretion in platelets. The process is subdivided into induction, transmission and execution. During induction the agents interact with membrane receptors that are specific for each indicidual agent. The subsequent transmission is identical for all inducers and is believed to make Ca2+ available in the cytosol which may trigger ATP-dependent processes, perhaps contractile mechanisms. It is hypothesized that the degree of the propagation of the basic platelet reaction is proportional to the concentration of cytocolic Ca2+ and that this concentration is proportional to the strength of the induction phase. At an early stage in this propagation, the membrane is induced to alter its form and at a later stage it is made adhesive toward other platelets' membranes. At still later stages, the process brings the membrane into contact with dense granules and α-granules. The execution of the measurable platelet functions can occur at these stages, but only when certain conditions are fulfilled. The dense granule secretion process is important, since the platelet aggregating agents ADP and cyclic endoperoxides are made available and increase the overall stimulus of the basic platelet reaction (positive feedback). Drugs and substances that inhibit aggregation can be subdivided into extrinsic and intrisic inhibitors. (author)

  10. Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267

    International Nuclear Information System (INIS)

    The mechanism of the release of arachidonic acid from phospholipids after the stimulation of guinea pig platelets with collagen, thrombin and platelet activating factor (PAF) was studied. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. Platelets were labeled with (14C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. In the present investigation it is shown that collagen, thrombin and PAF increased phospholipase C activity. It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. The guinea pig platelet is an ideal model to study phospholipase C-diacylglycerol lipase pathway for the release of arachidonic acid from platelet phospholipids because it does not have any phospholipase A2 activity. It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. Indomethacin completely inhibited collagen-induced platelet aggregation, was less effective against thrombin, and had no effect on PAF-induced platelet aggregation. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents

  11. Paraphenylene diamine exacerbates platelet aggregation and thrombus formation in response to a low dose of collagen.

    Science.gov (United States)

    Zaid, Younes; Marhoume, Fatimazahra; Senhaji, Nezha; Kojok, Kevin; Boufous, Hicham; Naya, Abdallah; Oudghiri, Mounia; Darif, Youssef; Habti, Norddine; Zouine, Soukaina; Mohamed, Fekhaoui; Chait, Abderahmane; Bagri, Abdellah

    2016-02-01

    Paraphenylene daimine (PPD) is an aromatic amine that is widely used in several industrial products; however, its toxicity has been reported in several cases of cardiac arrests. As platelets play a key role in cardiovascular diseases, we aimed to determine the impact of PPD in vitro and in vivo on platelet function. Our findings demonstrated that platelet activation and aggregation were strongly enhanced by PPD. Treatment with PPD primed human platelets that became more reactive in response to low doses of collagen. Furthermore, PPD exacerbated thrombus formation in rats in comparison with those untreated. Our results suggest that PPD is an important platelet primer predisposing platelets to promote thrombus formation in response to vascular injury. This should prompt the authorities to consider controlling the marketing of this product. PMID:26763399

  12. Palmitic acid-labeled lipids selectively incorporated into platelet cytoskeleton during aggregation

    International Nuclear Information System (INIS)

    Previous experiments showed that during the early stages (20-30 seconds) of aggregation induced by adenosine diphosphate (ADP, 2 microM) or thrombin (0.1 U/mL) of rabbit or human platelets prelabeled with [3H]palmitic acid, labeled lipid became associated with the cytoskeleton isolated after lysis with 1% Triton X-100, 5 mM EGTA [ethylene glycol-bis-(beta-aminoethyl ether)]-N,N,N',N'-tetra-acetic acid. The association appeared to be related to the number of sites of contact and was independent of the release of granule contents. We have now investigated the nature of the labeled lipids by thin-layer and column chromatography and found differences between the distribution of the label in intact platelets (both stimulated and unstimulated) and the isolated cytoskeletons. In both species, and with either ADP or thrombin as aggregating agent, 70-85% of the label in both intact platelets and in the cytoskeletons was in phospholipids. The distribution of label among the phospholipids in the cytoskeletons was similar to that in intact platelets except that the percentage of label in phosphatidylcholine was significantly higher in the cytoskeletons of human platelets than in the intact platelets, and the percentage of label in phosphatidylserine/phosphatidylinositol was significantly lower in the cytoskeletons of rabbit platelets and thrombin-aggregated human platelets than in intact platelets. The cytoskeletons contained a lower percentage of label in triacylglycerol, diacylglycerol, and cholesterol ester than the intact platelets. Contrary to a report in the literature, we found no evidence for the incorporation of diacylglycerol and palmitic acid into the cytoskeleton

  13. Platelet activation and platelet-monocyte aggregate formation by the atherosclerotic plaque lipid lysophosphatidic acid

    OpenAIRE

    Haserück, Nadine

    2007-01-01

    Oxidized LDL and platelets play a central role in the pathogenesis of atherosclerosis and ischemic cardiovascular diseases. Lysophosphatidic acid (LPA) is a thrombogenic substance that accumulates in mildly-oxidized LDL and in human atherosclerotic lesions, and is responsible for the initial platelet activation, shape change, induced by mildly-oxidized LDL and extracts of lipid-rich atherosclerotic plaques (Siess et al., 1999 Proc Natl Acad Sci USA 1999). LPA directly induced platelet shape c...

  14. Comparative study of heavy and deuterium-depleted water on platelet aggregation

    International Nuclear Information System (INIS)

    The effects of timed incubation of PRP (Platelet-Rich Plasma) with various concentrations of deuterium-depleted or deuterated water were tested. Aggregation curves were obtained under constant stirring at 20 deg.C and at 37 deg.C, using 5 - 10 μM ADP as aggregation trigger, using a Specord photo colorimeter. Incubation with 10 % deuterated water showed a significant decrease in the aggregation curves, an effect consistent with the data in the literature. Incubation with deuterium depleted water in the same conditions showed a marked increase in the aggregation curves, which suggests a powerful pro-aggregating effect of deuterium depleted water. (authors)

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

    Directory of Open Access Journals (Sweden)

    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.

  16. The in vitro effect of aspirin on increased whole blood platelet aggregation in oral contraceptive users.

    Science.gov (United States)

    Norris, L A; Bonnar, J

    1994-05-01

    The effects of triphasic oral contraceptives on whole blood platelet aggregation in 36 Italian women are reported here. Aspirin's effects on platelet aggregation were also studied. 18 women took a triphasic oral contraceptive; 10 women took Trinordiol, while 8 took Trinovum for at least 90 days. The remaining 18 women took nothing and served as controls. The study was aligned with each woman's birth control pill cycle. Blood was taken daily on days 15-21 of their cycle. Either saline solution or acetylsalicylic acid was added to the blood samples and compared. All data was statistically analyzed using unpaired student's t-test. Effects of 3 aggregating agents, ADP, PAF, and EDTA, on platelet aggregation were studied. Arachidonic acid and adrenalin bitartrate were also studied in this manner. An increase in platelet aggregation was observed in women taking oral contraceptives. No difference was found between patients taking Trinordiol and those taking Trinovum. The results of this study indicate an increase in whole blood platelet sensitivity to collagen, adrenalin, and arachidonic acid when using oral contraceptives. Aspirin, at low doses, may have a role in preventing early thrombus formation in women taking oral contraceptives. PMID:8042198

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Estimation of anti-platelet drugs on human platelet aggregation with a novel whole blood aggregometer by a screen filtration pressure method

    OpenAIRE

    Sudo, Toshiki; Ito, Hideki; Ozeki, Yasushi; Kimura, Yukio

    2001-01-01

    The effects of anti-platelet drugs on human whole blood aggregation were evaluated using a novel whole blood aggregometer by a screen filtration pressure (SFP) method.The SFP whole blood aggregometer was found to successfully detect whole blood aggregation induced by ADP, collagen and TRAP by measuring the SFP of blood samples. The platelet aggregation threshold index (PATI), the concentration of agonist required with an inducing pressure rate of 50%, varied time-dependently after collection ...

  19. Anti-Platelet Activities of Polyozellin In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Eun-Ju Yang

    2015-09-01

    Full Text Available Purpose: Thrombosis and thromboembolic occlusions of blood vessels are a major complication in various peripheral vascular diseases. The agents for the inhibition of platelet function are recognized as key tools in the treatment of atherothrombosis. Therefore, it became a mainstay medication for a wide range of vascular diseases. Polyozellin (POZ, a major constituent of an edible mushroom Polyozellus multiplex, was reported to have anti-oxidant, anti-angiogenesis, anti-cancer, and anti-inflammatory effects. However, anti-platelet effect of POZ has not been investigated yet. Methods: In our study, the anti-platelet activities of POZ were measured by thrombin- or collagen-induced platelet aggregation in vitro, adenosine diphosphate (ADP-induced platelet aggregation in vivo, and the thrombus formation in vivo. Results: POZ effectively inhibited the platelet aggregation not only in vitro using freshly isolated human platelets, but also in vivo thrombin or collagen-induced platelet aggregation. In accordance with the anti-platelet activities in vitro, POZ enhanced anti-thrombotic effect in vivo pulmonary embolism model and arterial thrombosis model. Conclusion: These results indicate that POZ possesses anti-platelet activities and might be useful for developing the drug candidates or functional foods for treatment of cardiovascular diseases without side effects.

  20. Modulation of platelet aggregation by areca nut and betel leaf ingredients: roles of reactive oxygen species and cyclooxygenase.

    Science.gov (United States)

    Jeng, Jiiang-Huei; Chen, Shiao-Yun; Liao, Chang-Hui; Tung, Yuan-Yii; Lin, Bor-Ru; Hahn, Liang-Jiunn; Chang, Mei-Chi

    2002-05-01

    There are 2 to 6 billion betel quid (BQ) chewers in the world. Areca nut (AN), a BQ component, modulates arachidonic acid (AA) metabolism, which is crucial for platelet function. AN extract (1 and 2 mg/ml) stimulated rabbit platelet aggregation, with induction of thromboxane B2 (TXB2) production. Contrastingly, Piper betle leaf (PBL) extract inhibited AA-, collagen-, and U46619-induced platelet aggregation, and TXB2 and prostaglandin-D2 (PGD2) production. PBL extract also inhibited platelet TXB2 and PGD2 production triggered by thrombin, platelet activating factor (PAF), and adenosine diphosphate (ADP), whereas little effect on platelet aggregation was noted. Moreover, PBL is a scavenger of O2(*-) and *OH, and inhibits xanthine oxidase activity and the (*)OH-induced PUC18 DNA breaks. Deferoxamine, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and neomycin prevented AN-induced platelet aggregation and TXB2 production. Indomethacin, genistein, and PBL extract inhibited only TXB2 production, but not platelet aggregation. Catalase, superoxide dismutase, and dimethylthiourea (DMT) showed little effect on AN-induced platelet aggregation, whereas catalase and DMT inhibited the AN-induced TXB2 production. These results suggest that AN-induced platelet aggregation is associated with iron-mediated reactive oxygen species production, calcium mobilization, phospholipase C activation, and TXB2 production. PBL inhibited platelet aggregation via both its antioxidative effects and effects on TXB2 and PGD2 production. Effects of AN and PBL on platelet aggregation and AA metabolism is crucial for platelet activation in the oral mucosa and cardiovascular system in BQ chewers. PMID:11978487

  1. α- and γ-mangostin cause shape changes, inhibit aggregation and induce cytolysis of rat platelets.

    Science.gov (United States)

    Liu, Yingqiu; Park, Jung-Min; Chang, Kyung-Hwa; Chin, Young-Won; Lee, Moo-Yeol

    2015-10-01

    α- and γ-mangostin are natural xanthones isolated from mangosteen (Garcinia mangostana) and the major constituents responsible for the plant's diverse biological activities. In this study, the effects of α- and γ-mangostin on platelets were investigated based on their possible antiplatelet activity. Treatment of isolated platelets with α-mangostin resulted in attenuation of platelet aggregatory response to collagen, thrombin or ADP. Such antiaggregatory effects were concentration-dependent in ranges of 1-10 μM. Interestingly, α-mangostin alone induced shape changes in platelets at the same concentration, and higher levels, 25 and 50 μM caused platelet lysis. Similarly, γ-mangostin induced shape changes and inhibited aggregation at 2.5-25 μM, while 50 and 100 μM γ-mangostin exhibited cytotoxicity. Platelet shape change induced by α- and γ-mangostin was accompanied by increases in myosin light chain (MLC) phosphorylation. MLC phosphorylation and subsequent shape changes were prevented by pretreatment with Rho kinase (ROCK) inhibitor Y-27632, but not by the intracellular Ca(2+) chelating with BAPTA-AM and extracellular Ca(2+) removal. Cytolysis by both α- and γ-mangostin was abolished in the absence of extracellular Ca(2+). Taken together, α- and γ-mangostin have differential effects on platelets depending on their concentration, which includes inducing shape change, inhibiting aggregation and causing cytolysis. Platelet shape change is attributed to stimulation of the Rho/ROCK signaling pathway, while platelet lysis is presumably mediated by extracellular Ca(2+) influx. These results suggest that mangosteen consumption may have potential platelet effects, although the in vivo or clinical consequences have yet to be assessed. PMID:26343955

  2. Characterization of the effects of isoprostanes on platelet aggregation in human whole blood

    OpenAIRE

    Cranshaw, Julius H; Evans, Timothy W.; Mitchell, Jane A.

    2001-01-01

    We tested the effects of 11 commercially-available isoprostanes on platelet aggregation directly or when triggered by the thromboxane receptor agonist U46619 or collagen in healthy human citrated blood using a whole blood aggregometer.None of the isoprostanes tested triggered aggregation alone, nor facilitated aggregation by a sub-threshold dose of U46619 or collagen. Five isoprostanes inhibited aggregation (rank order of potency 8-iso PGE1>8-iso PGE2>8-iso PGF2α>8-iso PGF3α>8-iso-13,14-dihyd...

  3. Dermcidin isoform-2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction

    OpenAIRE

    Sarbashri Bank; Pradipta Jana; Smarajit Maiti; Santanu Guha; Sinha, A.K.

    2014-01-01

    The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause both acute coronary syndromes (ACS) and acute myocardial infarction (AMI). While the inhibition of platelet aggregation by acetyl salicylic acid was reported to produce beneficial effects in ACS, it failed to do in AMI. The concentration of a stress induced protein (dermcidin isoform-2) was much higher in AMI than that in ACS. Incubation of normal platelet rich plasma (PRP) with dermcidin showe...

  4. Inhibition of adenosine diphosphate-induced platelet aggregation by alpha-lipoic acid and dihydroquercetin in vitro

    OpenAIRE

    Ivan S Ivanov; Sidehmenova, Anastasia V.; Vera I Smol′yakova; Chernysheva, Galina A.; Plotnikov, Mark B.

    2014-01-01

    Objectives: To investigate the antiplatelet activity of alpha-lipoic acid (α-LA) and dihydroquercetin (DHQ). Materials and Methods: Antiplatelet activity of the α-LA and DHQ was evaluated in rich platelet plasma of rat. The platelet aggregation was induced by adenosine diphosphate (ADP) in concentration of 4 Χ 10 -5 Μ. Results: α-LA and DHQ inhibited platelet aggregation in concentration-dependent manner. The antiplatelet activity of α-LA was more pronounced than DHQ. DHQ also increas...

  5. Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate

    Science.gov (United States)

    Homer, Kerry L; Wanstall, Janet C

    2002-01-01

    Inhibition of rat platelet aggregation by the nitric oxide (NO) donor MAHMA NONOate (Z-1-{N-methyl-N-[6-(N-methylammoniohexyl)amino]}diazen-1-ium-1,2-diolate) was investigated. The aims were to compare its anti-aggregatory effect with vasorelaxation, to determine the effects of the soluble guanylate cyclase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), and to investigate the possible role of activation of sarco-endoplasmic reticulum calcium-ATPase (SERCA), independent of soluble guanylate cyclase, using thapsigargin. MAHMA NONOate concentration-dependently inhibited sub-maximal aggregation responses to collagen (2–10 μg ml−1) and adenosine diphosphate (ADP; 2 μM) in platelet rich plasma. It was (i) more effective at inhibiting aggregation induced by collagen than by ADP, and (ii) less potent at inhibiting platelet aggregation than relaxing rat pulmonary artery. ODQ (10 μM) caused only a small shift (approximately half a log unit) in the concentration-response curve to MAHMA NONOate irrespective of the aggregating agent. The NO-independent activator of soluble guanylate cyclase, YC-1 (3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole; 1–100 μM), did not inhibit aggregation. The cGMP analogue, 8-pCPT-cGMP (8-(4-chlorophenylthio)guanosine 3′5′ cyclic monophosphate; 0.1–1 mM), caused minimal inhibition. On collagen-aggregated platelets responses to MAHMA NONOate (ODQ 10 μM present) were abolished by thapsigargin (200 nM). On ADP-aggregated platelets thapsigargin caused partial inhibition. Results with S-nitrosoglutathione (GSNO) resembled those with MAHMA NONOate. Glyceryl trinitrate and sodium nitroprusside were poor inhibitors of aggregation. Thus inhibition of rat platelet aggregation by MAHMA NONOate (like GSNO) is largely ODQ-resistant and, by implication, independent of soluble guanylate cyclase. A likely mechanism of inhibition is activation of SERCA. PMID:12429580

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

    DEFF Research Database (Denmark)

    Kuijpers, Marijke J E; Megens, Remco T A; Nikookhesal, Elham; Feijge, Marion A H; De Mey, J G R; oude Egbrink, Mirjam G A; van Giezen, J J J; Heemskerk, Johan W M

    2011-01-01

    . At later time points, large thrombi formed in the clopidogrel but not in the ticagrelor group, and unprotected, juvenile platelets preferentially incorporated into the formed thrombi. However, platelets from both groups were still similarly reduced in assays of whole blood aggregation. Conclusively...... after drug cessation have not been investigated. We treated WKY rats with a single, high dose of 200 mg/kg clopidogrel or 40 mg/kg ticagrelor. Blood was collected at different time points after treatment. Flow cytometry confirmed full platelet protection against ADP-induced αIIbβ₃ activation shortly...... after clopidogrel or ticagrelor treatment. At later time points after clopidogrel treatment, a subpopulation of juvenile platelets appeared that was fully responsive to ADP. Addition of ticagrelor to clopidogrel-treated blood reduced αIIbβ₃ activation of the unprotected platelets. In contrast, at later...

  7. The effect of oral phenylbutazone on whole blood platelet aggregation in the dog.

    OpenAIRE

    Jackson, M. L.; Searcy, G. P.; Olexson, D W

    1985-01-01

    Platelet aggregation to collagen, arachidonic acid and adenosine diphosphate was evaluated in six dogs using a whole blood electronic aggregometer. The six dogs were then given phenylbutazone orally according to four different dosage levels and durations of treatment. Aggregation responses were measured at established intervals of time following phenylbutazone administration. Data on untreated dogs indicated that arachidonic acid, at a final concentration of 50 micrograms/mL and collagen, at ...

  8. Activation of platelet aggregation and arachidonate metabolism in early stage of acute radiation injury

    International Nuclear Information System (INIS)

    The paper describes the changes of platelet aggregation and arachidonate metabolism in platelets and endothelial cells after 8.0-8.5 Gy γ-ray whole-body irradiation in rats. It was found that with 8.0 Gy exposure platelet aggregation rate and speed, and plasma TxB2 level were increased at 4h and on the 1st day post irradiation, and that 6-keto-PGF1α level was enhanced at 4h, then reduced to the control level on the 1st day post irradiation. The result of biological assay showed the ability for rat platelets to convert exogenous arachidonate into TxA2 was significantly raised at 4h and on the 1st day after 8.5 Gy γ-ray irradiation. It is suggested that the activation of platelet arachidonate metabolism may be one of the important causes of acute radiation injury is suggested that the activation of platelet arachidonate metabolism may be one of the important causes of acute radiation injury

  9. 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.

  10. Does the magnetic field of a magnetic stirrer in an optical aggregometer affect concurrent platelet aggregation?

    Science.gov (United States)

    Sagdilek, Engin; Sebik, Oguz; Celebi, Gurbuz

    2013-07-01

    Platelets are subjected to extremely low frequency electromagnetic fields during standard aggregometry measurements owing to the use of a magnetic stir bar in the instrument. This study evaluates the effects of this magnetic field exposure on platelet aggregation by comparing the results obtained in a modified aggregometer. Blood samples from healthy volunteers were anticoagulated using citrate or heparin. Platelet-rich plasma (PRP) samples were prepared. A mechanical stirring device was attached to the aggregometer instead of the magnetic stir bar system. The PRP samples were stirred using a stirring rod tip that did not produce any magnetic fields in one channel of the aggregometer; in the other channel, a stirring rod carrying a small magnet at its tip was used. As a result, a magnetic field in the extremely low frequency range and in the amplitude range of 1.9-65 mT was applied to the platelets assigned to the channel where the magnetic stirring rod tip was used. Aggregation was induced using adenosine diphosphate (ADP), collagen, or epinephrine. The slopes, maximum aggregation values, and areas under the aggregation curves were compared between the magnetic and neutral stirring rod tip groups. For samples stirred with the magnetic stirring rod tip, a significant decrease was observed in 12 of the 14 parameters evaluated for aggregations induced with ADP or collagen compared to the neutral stirring rod tip, regardless of the method used for anticoagulation. This observation indicates that the magnetic stir bars used in standard aggregometry may significantly alter aggregation parameters and platelets may be possible targets of electromagnetic fields. PMID:23436227

  11. 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

    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 <0.01. When the erect posture was assumed after lying at ease for 1 h after exercise, it did not increase platelet activity as expected, but caused a modest increase...

  12. 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.

  13. 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

  14. A laser flow aggregometer for measurement of white blood cell and platelet aggregation

    International Nuclear Information System (INIS)

    The measurement of aggregation of white blood cells and platelets is important in understanding cardiovascular disease. A new aggregometer has been developed, based on a laser flow cytometer. Pulses detected using a high speed photodiode are acquired to a computer and analysed. Tests based on separated white cells, platelets and whole blood samples have been carried out to evaluate this system. Results show that the laser flow cytometer system has a much better resolution and wider dynamic range than existing electronic flow cytometer instruments. As a result, more details of platelet and white blood cell aggregation profiles can be obtained. The new aggregometer is now being used in clinical trials on patients with vascular disease, for comparison with commercial systems. (author)

  15. Formulation and Storage of Platelet-Rich Plasma Homemade Product

    Science.gov (United States)

    Giraudo, Laurent; Veran, Julie; Magalon, Jeremy; Coudreuse, Jean-Marie; Magalon, Guy; Dubois, Christophe; Serratrice, Nicolas; Dignat-George, Françoise; Sabatier, Florence

    2012-01-01

    Abstract The platelet-rich plasma (PRP) is an autologous biotherapy based on platelet-healing properties. Here, we developed a simple and reproducible PRP purification protocol based on two successive centrifugations. We evaluated different centrifugation speeds and time-storage durations on the platelet quantity and quality. Sterility and stability of our PRP homemade product were also performed. We prepared PRP from 54 healthy volunteers. We tested activation state, reactivity, and stability of platelets by flow cytometry using basal and adenosine diphosphate (ADP)-induced P-selectin expression markers; growth factor release after platelet activation by an enzyme-linked immunosorbent assay (ELISA); platelet aggregation capacity by aggregrometry assays; clot formation and retraction by thromboelastography; and platelet morphology by ultrastructural analysis. About 130 and 250 g successive speed centrifugations further concentrated platelets while preserving their bioactivity during 6 h (after that, platelet functions were significantly altered). In these conditions, we obtained a highly concentrated pure PRP product (with a low leukocyte count) suitable to study platelet properties. To avoid the loss of efficacy, we recommend injecting PRP under 3 h after preparation. PMID:23516671

  16. PLATELET AGGREGATION AND ANTI-INFLAMMATORY EFFECTS OF GARDEN PEA, DESI CHICKPEA AND KABULI CHICKPEA

    Czech Academy of Sciences Publication Activity Database

    ZIA-UL-HAQ, M.; ALI KHAN, B.; Landa, Přemysl; Kutil, Zsófia; AHMED, S.; QAYUM, M.; Ahmad, S.

    2012-01-01

    Roč. 69, č. 4 (2012), s. 707-711. ISSN 0001-6837 Institutional research plan: CEZ:AV0Z50380511 Keywords : platelet aggregation * Garden pea * Desi chickpea Subject RIV: EF - Botanics Impact factor: 0.665, year: 2012 http://home.ueb.cas.cz/publikace/2012_Haq_ACTA_POLONIAE_PHARMACEUTICA_707.pdf

  17. Variability of the human aggregation response of normal platelets to AVP

    Czech Academy of Sciences Publication Activity Database

    Pencheva, N.; Barth, Tomislav; Barthová, J.; Penev, M.; Mladenova, A.

    Praha : ÚOCHB AV ČR, 2003 - (Slaninová, J.), s. 73-76 ISBN 80-86241-20-3. [Biologically Active Peptides /8./. Praha (CZ), 23.04.2003-25.04.2003] Institutional research plan: CEZ:AV0Z4055905 Keywords : vasopressin * platelet aggregation * heparin Subject RIV: CE - Biochemistry

  18. Echistatin. A potent platelet aggregation inhibitor from the venom of the viper, Echis carinatus.

    Science.gov (United States)

    Gan, Z R; Gould, R J; Jacobs, J W; Friedman, P A; Polokoff, M A

    1988-12-25

    A 49-residue protein, echistatin, which inhibits platelet aggregation, was purified from the venom of the saw-scaled viper Echis carinatus. The purification procedure included gel filtration on Sephadex G-50, cation-exchange chromatography on Mono S, and C18 reverse-phase high pressure liquid chromatography. The purified protein was homogeneous as judged by polyacrylamide gel electrophoresis, isoelectric focusing, reverse-phase high pressure liquid chromatography, and NH2-terminal sequence analysis. Echistatin is a single-chain polypeptide with a molecular weight of 5400 and a native isoelectric point of 8.3. The most abundant amino acid, cysteine, accounts for 8 of the 49 residues in the protein. A 10-residue segment of echistatin shows 90% identity to a portion of the sequence of trigramin, a platelet aggregation inhibitor from the green tree viper Trimereserus gramineus (Huang, T.-F., Holt, J. C., Lukasiewicz, H., and Niewiarowski, S. (1987) J. Biol. Chem. 262, 16157-16163). Echistatin contains the sequence arginine-glycine-aspartic acid, which is common to proteins which bind to the glycoprotein IIb/IIIa complex. It also contains the sequence proline-arginine-asparagine-proline, which is found in the A alpha chain of human fibrinogen at position 267-270. The purified protein inhibits fibrinogen-dependent platelet aggregation initiated by ADP with an IC50 of 3 x 10(-8) M and also prevents aggregation initiated by thrombin, epinephrine, collagen, or platelet-activating factor. Reduction of echistatin abolished its inhibitory activity. PMID:3198653

  19. Effect of catheter flush fluids on blood coagulation and aggregation of platelets

    International Nuclear Information System (INIS)

    The effect upon blood coagulation and aggregation of platelets of a polysaccharide catheter flush fluid (flush fluid E) was investigated and compared with isotonic saline and Isopaque Cerebral. The result indicates that flush fluid E does not activate the coagulation system. (Auth.)

  20. The effect of naloxone and cyproheptadine on pulmonary platelet trapping, hypotension, and platelet aggregability in traumatized dogs

    Energy Technology Data Exchange (ETDEWEB)

    Almqvist, P.; Kuenzig, M.; Schwartz, S.I.

    1983-05-01

    Adult respiratory distress syndrome (ARDS) is a serious complication of trauma and sepsis. We have earlier shown naloxone, an opiate antagonist, and cyproheptadine, an antiserotonin drug, to be effective in reducing pulmonary platelet trapping (PPT), which is thought to play an important role in the evolution of ARDS in endotoxin-shocked dogs. Endorphins are implicated as pathophysiologic factors in shock, and serotonin is a possible mediator of their action. The present study shows naloxone and cyproheptadine to be equally effective in protecting against PPT in dogs subjected to trauma, and when naloxone is given before the trauma it also obviates the hypotension associated with trauma. In addition, the naloxone- and cyproheptadine-treated animals did not show the increased platelet aggregability usually seen in traumatized dogs.

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

    International Nuclear Information System (INIS)

    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 3H-arachidonic acid and 14C-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 14C-serotonin and 3H-arachidonic acid metabolites, it appeared that either release of 14C and 3H 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 14C and 3H

  2. Platelet aggregation inhibitors from Philippine marine invertebrate samples screened in a new microplate assay.

    Science.gov (United States)

    Pimentel, Sheila Marie V; Bojo, Zenaida P; Roberto, Amy V D; Lazaro, Jose Enrico H; Mangalindan, Gina C; Florentino, Leila M; Lim-Navarro, Pilar; Tasdemir, Deniz; Ireland, Chris M; Concepcion, Gisela P

    2003-01-01

    A new microplate assay for Ca(2+)-induced platelet aggregation as detected by Giemsa dye was used to screen marine invertebrate samples from the Philippines for inhibitors of human platelet aggregation. Out of 261 crude methanol extracts of marine sponges and tunicates, 25 inhibited aggregation at 2 mg/ml. Inhibition of agonist-induced aggregation in an aggregometer was used to confirm results of the microplate assay and to determine the specific mode of inhibition of 2 samples. The marine sponge Xestospongia sp. yielded a xestospongin/araguspongine-type molecule that inhibited collagen-induced aggregation by 87% at 2 micro g/ml, and epinephrine-induced aggregation by 78% at 20 micro g/ml, while the marine sponge Aplysina sp. yielded 5,6-dibromotryptamine, which inhibited epinephrine-induced aggregation by 51% at 20 micro g/ml. In this study we have found that the microplate assay is a simple, inexpensive, yet useful preliminary tool to qualitatively screen a large number of marine samples for antiplatelet aggregation activity. PMID:14719168

  3. Anagrelide, a potent inhibitor of platelet aggregation, inhibits inositol phosphate generation and elevates cAMP

    International Nuclear Information System (INIS)

    The effects of the potent platelet aggregation inhibitor, anagrelide (6,7-dichloro-1,5-dihydroimidazo[2,1-6]quinazolin-2(3H)-one monohydrochloride; BL-4162A), on polyphosphoinositide metabolism in human platelets was investigated. Anagrelide maximally inhibited the thrombin-stimulated increase in inositol phosphates (IPn) at approximately 3.3 x 10-6M. The time of incubation required for a maximal response was between 15 and 30 min. Since anagrelide has been reported to inhibit low-Km cAMP phosphodiesterase, the authors compared its ability to inhibit stimulated IPn to that of the well known cAMP phosphodiesterase inhibitor IBMX. Both compounds inhibited IPn similarly except in experiments in which the IP phosphatase inhibitor, lithium chloride, was omitted. In these experiments, anagrelide totally inhibited, while IBMX only partially inhibited, the thrombin-stimulated elevation of IPn. The effect of anagrelide on platelet cyclic nucleotide levels was also measured. After 30 min incubation, concentrations of anagrelide which maximally inhibit aggregation induced a 2-fold increase in cAMP without significantly altering cGMP. These results suggest the mechanism of platelet aggregation inhibition includes an anagrelide-induced elevation of cAMP

  4. Inhibition of Platelet Aggregation by the Leaf Extract of Carica papaya During Dengue Infection: An In Vitro Study.

    Science.gov (United States)

    Chinnappan, Shobia; Shettikothanuru Ramachandrappa, Vijayakumar; Tamilarasu, Kadhiravan; Krishnan, Uma Maheswari; Balakrishna Pillai, Agiesh Kumar; Rajendiran, Soundravally

    2016-04-01

    Dengue cases were reported to undergo platelet activation and thrombocytopenia by a poorly understood mechanism. Recent studies suggested that Carica papaya leaf extract could recover the platelet count in dengue cases. However, no studies have attempted to unravel the mechanism of the plant extract in platelet recovery. Since there are no available drugs to treat dengue and considering the significance of C. papaya in dengue treatment, the current study aimed to evaluate two research questions: First one is to study if the C. papaya leaf extract exerts its action directly on platelets and second one is to understand if the extract can specifically inhibit the platelet aggregation during dengue viral infection. Sixty subjects with dengue positive and 60 healthy subjects were recruited in the study. Platelet-rich plasma (PRP) and platelet-poor plasma were prepared from both the dengue-infected and healthy control blood samples. Effect of the leaf extract obtained from C. papaya leaves was assessed on plasma obtained as well as platelets collected from both healthy and dengue-infected individuals. Platelet aggregation was significantly reduced when leaf extract preincubated with dengue plasma was added into control PRP, whereas no change in aggregation when leaf extract incubated-control plasma was added into control PRP. Upon direct addition of C. papaya leaf extract, both dengue PRP and control PRP showed a significant reduction in platelet aggregation. Within the dengue group, PRP from severe and nonsevere cases showed a significant decrease in aggregation without any difference between them. From the study, it is evident that C. papaya leaf extract can directly act on platelet. The present study, the first of its kind, found that the leaf extract possesses a dengue-specific neutralizing effect on dengue viral-infected plasma that may exert a protective role on platelets. PMID:26910599

  5. Aluminum induces lipid peroxidation and aggregation of human blood platelets

    OpenAIRE

    T.J.C. Neiva; D.M. Fries; Monteiro, H. P.; E.A. D'Amico; D.A.F. Chamone

    1997-01-01

    Aluminum (Al3+) intoxication is thought to play a major role in the development of Alzheimer's disease and in certain pathologic manifestations arising from long-term hemodialysis. Although the metal does not present redox capacity, it can stimulate tissue lipid peroxidation in animal models. Furthermore, in vitro studies have revealed that the fluoroaluminate complex induces diacylglycerol formation, 43-kDa protein phosphorylation and aggregation. Based on these observations, we postulated t...

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

    International Nuclear Information System (INIS)

    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

  7. The role of plasma lipid photo-oxidation in the decrease of the aggregation of platelets under UV irradiation

    International Nuclear Information System (INIS)

    Change of platelet aggregation dependent on blood plasma under irradiation of plasma enriched with platelets and serium (1) as well as the role of peroxide photooxidation on non-saturated fatty acids (2) have been studied. Based on the obtained data it is concluded that peroxide photooxidation and stimulation of dark oxidation of their lipids under UV-radiation effect on blood plasma or serium. Products of these reactions weaken aggregation of platelets suspended in serum (plasma). Platelets destroy products of peroxide oxidation of plasma lipids, and as a result aggregation of cells is gradually reduced under incubation of platelet and plasma mixture irradiatted in darkness. It is supposed that photooxidation of blood lipids produces curative properties to blood under UV-radiation

  8. Protective Mechanisms of Guanosine from Solanum lycopersicum on Agonist-Induced Platelet Activation: Role of sCD40L

    Directory of Open Access Journals (Sweden)

    Iván Palomo

    2013-07-01

    Full Text Available In the past 30 years, only three natural products have been sources of new drugs with antiplatelet activity. In this study, we have demonstrated for the first time that guanosine from Solanum lycopersicum possesses antiplatelet (secretion, spreading, adhesion and aggregation activity in vitro and inhibition of platelet inflammatory mediator of atherosclerosis (sCD40L. According to ADP-induced platelet aggregation inhibiting, the total extract residue was fractionated by liquid chromatography/phase separation, affording an aqueous fraction. This fraction was subjected to repeated permeation over Sephadex LH-20 and semi-preparative TLC. The isolated compound finally obtained was identified as guanosine on the basis of its UV-spectra, HPLC and 1H-NMR data. Guanosine concentration dose-dependently (1 to 4 mmol/L inhibited platelet secretion and aggregation induced by ADP and collagen. Spread of human platelets on collagen in the presence of guanosine was fully inhibited. After incubation of whole blood with guanosine, the platelet adhesion and aggregation under flow conditions was inhibited concentration dependently (0.2 to 2 mmol/L. At the same concentrations that guanosine inhibits platelet aggregation, levels of sCD40L were significantly decreased. Guanosine is thus likely to exert significant protective effects in thromboembolic-related disorders by inhibiting platelet aggregation.

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

    International Nuclear Information System (INIS)

    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)

  10. Pistacia chinensis Methanolic Extract Attenuated MAPK and Akt Phosphorylations in ADP Stimulated Rat Platelets In Vitro.

    Science.gov (United States)

    Park, Ji Young; Hong, Mei; Jia, Qi; Lee, Young-Chul; Yayeh, Taddesse; Hyun, Eujin; Kwak, Dong-Mi; Cho, Jae Youl; Rhee, Man Hee

    2012-01-01

    Pistacia chinensis (Chinese pistache) is a widely grown plant in southern China where the galls extract is a common practice in folk medicine. However, extracts from this plant have never been attempted for their cardiovascular protective effects in experimental setting. Here therefore we aimed to investigate the antiplatelet activity of Pistacia chinensis methanolic extract (PCME) in ADP stimulated rat platelets in vitro. PCME (2.5-20 μg/mL) inhibited ADP-induced platelet aggregation. While PCME diminished [Ca(2+)]i, ATP, and TXA2 release in ADP-activated platelets, it enhanced cAMP production in resting platelets. Likewise, PCME inhibited fibrinogen binding to αIIbβ3 and downregulated JNK, ERK, and Akt phosphorylations. Thus, PCME contains potential antiplatelet compounds that could be deployed for their therapeutic values in cardiovascular pathology. PMID:22899962

  11. Effects of corydalis amabilis Migo total alkaloids on platelet cyclic AMP and cyclic GMP

    International Nuclear Information System (INIS)

    Corydalis amabilis Migo total alkaloids (COAMTA), isolated from the root of Corydalis decumbens (Thunb) Pers, possessed inhibitory action on ADP-induced blood platelet aggregation and the formation of thrombus in animal experiments. Its effects on the platelet cyclic AMP and cyclic GMP in incubated rabbit platelet were measured by radioimmunoassay. cAMP was significantly elevated when COAMTA was given 0.08-0.16 mg/ml PRP. In concentration up to 0.16 mg/ml PRP, COAMTA elevated cGMP, but the ratio value of cAMP/cGMP was much higher than that of control group. These results suggest that the anti-platelet activity of COAMTA were mediated through elevation of cAMP levels

  12. Atick salivary protein targets cathepsin G and chymase and inhibits host inflammation and platelet aggregation

    Czech Academy of Sciences Publication Activity Database

    Chmelař, Jindřich; Oliveira, C. J.; Řezáčová, Pavlína; Francischetti, I.M.B.; Kovářová, Zuzana; Pejler, G.; Kopáček, Petr; Ribeiro, J.M.C.; Mareš, Michael; Kopecký, Jan; Kotsyfakis, Michalis

    2011-01-01

    Roč. 117, č. 2 (2011), s. 736-744. ISSN 0006-4971 R&D Projects: GA AV ČR IAA600960811; GA MŠk(CZ) LC06009; GA ČR(CZ) GAP207/10/2183 Institutional research plan: CEZ:AV0Z60220518; CEZ:AV0Z40550506 Keywords : parasite serpin * IRS-2 * tick * Ixodes ricinus * platelet aggregation * inflammation * cathepsin G * chymase Subject RIV: EC - Immunology Impact factor: 9.898, year: 2011

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

    OpenAIRE

    T.J.C. Neiva; A.L. Benedetti; S.M.C.N. Tanaka; Santos, J. I.; E.A. D'Amico

    2002-01-01

    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 thiobarbitur...

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

    OpenAIRE

    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:...

  15. Defective platelet aggregation to the calcium ionophore A23187 in a patient with a lifelong bleeding disorder.

    OpenAIRE

    Machin, S J; Keenan, J. P.; McVerry, B A

    1983-01-01

    A patient with a lifelong bleeding disorder is presented with a prolonged bleeding time and abnormal aggregation and secretion responses to arachidonic acid, thromboxane A2, PAF-acether and the divalent calcium ionophore A23187. Platelet alpha and dense granule contents and morphology appear normal. The proposed defect is due to an abnormality of a platelet intracellular calcium dependent process.

  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. Impaired platelet aggregation and sustained bleeding in mice lacking the fibrinogen motif bound by integrin alpha IIb beta 3.

    OpenAIRE

    Holmbäck, K; Danton, M J; Suh, T T; Daugherty, C. C.; Degen, J L

    1996-01-01

    Blood loss at sites of vascular rupture is controlled by the adhesion and aggregation of platelets and the formation of an insoluble fibrin matrix. Fibrinogen is considered to be critical in these processes by both providing an abundant dimeric ligand for alpha IIb beta 3-mediated platelet aggregation, and serving as the fundamental building block of the fibrin polymer. To establish an in vivo model system to examine in detail the importance of alpha IIb beta 3-fibrinogen interactions in plat...

  18. An antagonistic activity of etizolam on platelet-activating factor (PAF). In vitro effects on platelet aggregation and PAF receptor binding.

    Science.gov (United States)

    Mikashima, H; Takehara, S; Muramoto, Y; Khomaru, T; Terasawa, M; Tahara, T; Maruyama, Y

    1987-08-01

    The antagonistic effect of etizolam, an anti-anxiety drug, on platelet-activating factor (PAF) was investigated in rabbit platelets in vitro. Etizolam inhibited PAF-induced aggregation in a dose-dependent manner, with an IC50 of 3.8 microM, about one tenth that of triazolam (IC50 = 30 microM). At 300 microM, it inhibited both ADP and arachidonic acid-induced aggregation only slightly, while the other anti-anxiety drugs tested had no effect on PAF-induced aggregation even at this concentration. Etizolam and triazolam inhibited the specific binding of 3H-PAF to PAF receptor sites on washed rabbit platelets with IC50 values of 22 nM and 320 nM, respectively. Diazepam and estazolam were inactive even at 1 microM. These results indicate that etizolam is a specific antagonist of PAF. PMID:2890779

  19. Identification of a novel platelet antagonist that binds to CLEC-2 and suppresses podoplanin-induced platelet aggregation and cancer metastasis.

    Science.gov (United States)

    Chang, Yao-Wen; Hsieh, Pei-Wen; Chang, Yu-Tsui; Lu, Meng-Hong; Huang, Tur-Fu; Chong, Kowit-Yu; Liao, Hsiang-Ruei; Cheng, Ju-Chien; Tseng, Ching-Ping

    2015-12-15

    Podoplanin (PDPN) enhances tumor metastases by eliciting tumor cell-induced platelet aggregation (TCIPA) through activation of platelet C-type lectin-like receptor 2 (CLEC-2). A novel and non-cytotoxic 5-nitrobenzoate compound 2CP was synthesized that specifically inhibited the PDPN/CLEC-2 interaction and TCIPA with no effect on platelet aggregation stimulated by other platelet agonists. 2CP possessed anti-cancer metastatic activity in vivo and augmented the therapeutic efficacy of cisplatin in the experimental animal model without causing a bleeding risk. Analysis of the molecular action of 2CP further revealed that Akt1/PDK1 and PKCμ were two alternative CLEC-2 signaling pathways mediating PDPN-induced platelet activation. 2CP directly bound to CLEC-2 and, by competing with the same binding pocket of PDPN in CLEC-2, inhibited PDPN-mediated platelet activation. This study provides evidence that 2CP is the first defined platelet antagonist with CLEC-2 binding activity. The augmentation in the therapeutic efficacy of cisplatin by 2CP suggests that a combination of a chemotherapeutic agent and a drug with anti-TCIPA activity such as 2CP may prove clinically effective. PMID:26528756

  20. The role of plasmalipid photo-oxidation in the decrease of the aggregation of platelets under IV irradiation

    International Nuclear Information System (INIS)

    Peroxide photooxidation and stimulation of dark oxidation of lipids are stated to take place under UV-radiation effect on plasma or blood serum. Products of these reactions weaken aggregation of platelets suspended in serum (plasma). Platelets destroy products of peroxide oxidation of plasma lipids, as a result, aggregation of cells is gradually reproduced at incubation of irradiated mixture of platelets and plasma in the darkness. It is not excluded that photooxidation of blood lipids imparts curing properties to blood under UV-radiation

  1. 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 aggregation (by 31-41% for raspberry and by 38-55% for dewberry, P aggregation. The effectiveness of the extracts in whole blood and the lack of their activity in PRP indicate that leukocytes are likely to participate in the platelet response to the extracts. Our experiments show that the extracts significantly reduced the amount of free radicals released by activated neutrophils in whole blood (P aggregation. In summary, our findings show that the 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. PMID:26836594

  2. Dermcidin isoform-2 induced nullification of the effect of acetyl salicylic acid in platelet aggregation in acute myocardial infarction

    Science.gov (United States)

    Bank, Sarbashri; Jana, Pradipta; Maiti, Smarajit; Guha, Santanu; Sinha, A. K.

    2014-01-01

    The aggregation of platelets on the plaque rupture site on the coronary artery is reported to cause both acute coronary syndromes (ACS) and acute myocardial infarction (AMI). While the inhibition of platelet aggregation by acetyl salicylic acid was reported to produce beneficial effects in ACS, it failed to do in AMI. The concentration of a stress induced protein (dermcidin isoform-2) was much higher in AMI than that in ACS. Incubation of normal platelet rich plasma (PRP) with dermcidin showed one high affinity (Kd = 40 nM) and one low affinity binding sites (Kd = 333 nM). When normal PRP was incubated with 0.4 μM dermcidin, the platelets became resistant to the inhibitory effect of aspirin similar to that in the case of AMI. Incubation of PRP from AMI with dermcidin antibody restored the sensitivity of the platelets to the aspirin effect. Incubation of AMI PRP pretreated with 15 μM aspirin, a stimulator of the NO synthesis, resulted in the increased production of NO in the platelets that removed the bound dermcidin by 40% from the high affinity binding sites of AMI platelets. When the same AMI PRP was retreated with 10 μM aspirin, the aggregation of platelets was completely inhibited by NO synthesis. PMID:25055737

  3. Changes in blood platelet aggregation in two leukaemic patients after receiving large dose of γ-irradiation

    International Nuclear Information System (INIS)

    This paper presents the results of platelet aggregation determination in two patients with leukaemia after irradiation with large doses of γ-rays. It is shown that in the early days after irradiation an increase of aggregation response appeared. Perhaps it is one of the causes of post-irradiation microcirculatory disturbances. We are inclined to say that the inhibition of platelet aggregation during early days after irradiation would be helpful to alleviate microcirculatory disturbances, thereby the repair of radiation damage might be brought about

  4. Effect of ticlopidine ex vivo on platelet intracellular calcium mobilization

    Energy Technology Data Exchange (ETDEWEB)

    Derian, C.K.; Friedman, P.A.

    1988-04-01

    The antiplatelet compound ticlopidine exerts its potent inhibitory activity through an as yet undetermined mechanism(s). The goal of this study was to determine the effect, if any, of ticlopidine ex vivo on platelet calcium mobilization. Ticlopidine inhibited ADP-induced platelet aggregation by 50-80%. In the presence of 1 mM EGTA, ticlopidine inhibited ADP- and thrombin-stimulated increases in (Ca2+)i in fura-2 loaded platelets. We evaluated further the effect of ticlopidine on calcium mobilization by examining both agonist-stimulated formation of inositol trisphosphate in intact platelets and the ability of inositol trisphosphate to release /sup 45/Ca from intracellular sites in permeabilized cells. We show here that while ticlopidine significantly affected agonist-induced intracellular calcium mobilization in intact platelets, the drug was without effect on agonist-stimulated formation of inositol trisphosphate in intact platelets and on inositol trisphosphate-induced /sup 45/Ca release in saponin-permeabilized platelets. Our study demonstrates that ticlopidine exerts at least part of its effect via inhibition of intracellular calcium mobilization but that its site of action remains to be determined.

  5. Effects of class I heparin binding growth factor and fibronectin on platelet adhesion and aggregation

    International Nuclear Information System (INIS)

    Fibronectin and heparin binding growth factor-type 1 have been affixed to vascular graft surfaces to enhance the attachment and the proliferation of transplanted endothelial cells, respectively. The current study examines the effect of fibronectin and heparin binding growth factor-type 1 on platelet adhesion and activation in vivo and on platelet aggregation in vitro. Expanded polytetrafluoroethylene prostheses (5 cm x 4 mm internal diameter) were treated either with fibronectin (n = 9), fibronectin/heparin/heparin binding growth factor-type 1/heparin (n = 12), or neither (n = 13) and were interposed into canine aortoiliac systems bilaterally. Autogenous radiolabeled (Indium 111 oxine, 650 microCi) platelets were injected intravenously before reestablishment of circulation. Perfusion was maintained for 30 minutes, and prostheses were removed with segments of native aorta and distal iliac arteries bilaterally. Specimens were examined for thrombus-free surface area, by gamma well counting for adherent radiolabeled platelets, and by light microscopy and transmission and scanning electron microscopic techniques. Results showed that both the fibronectin and fibronectin/heparin/heparin binding growth factor-type 1/heparin pretreated prostheses contained significantly greater numbers of platelets and adherent radioactivity than did control graft segments when normalized to their ipsilateral iliac arteries. Fibronectin/heparin/heparin binding growth factor-type 1/heparin pretreated prostheses contained 27 +/- 16 times more radioactivity per square millimeter than ipsilateral iliac arteries, fibronectin pretreated prostheses had 13 +/- 8 times more radioactivity per square millimeter than ipsilateral iliac arteries, and untreated expanded polytetrafluoroethylene had 4 +/- 3 times more radioactivity per square millimeter than ipsilateral iliac arteries

  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. Mediation of endothelin-1-induced inhibition of platelet aggregation via the ETB receptor.

    OpenAIRE

    McMurdo, L.; Lidbury, P. S.; Thiemermann, C.; Vane, J. R.

    1993-01-01

    1. The effects of FR139317 (ETA antagonist) or PD145065 (non-selective ETA/ETB antagonist) on endothelin-1 (ET-1)-induced changes in blood pressure and inhibition of ex vivo platelet aggregation were investigated in the anaesthetized rabbit. 2. ET-1 (1 nmol kg-1, i.a. bolus) caused a sustained increase in mean arterial pressure (MAP) (peak increase 47 +/- 5 mmHg, n = 8). Intravenous infusion of FR139317 at 0.2 (n = 4) or 0.6 mg kg-1 min-1 (n = 4) inhibited the ET-1 pressor response by 83 or 8...

  8. [Coumarins from Leonurus japonicus and their anti-platelet aggregative activity].

    Science.gov (United States)

    Yang, Huai; Zhou, Qin-mei; Peng, Cheng; Liu, Lu-si; Xie, Xiao-fang; Xiong, Liang; Liu, Zhao-hua

    2014-11-01

    Chemical constituents of Leonurus japonicus were isolated and purified by a combination of various chromatographic techniques including column chromatography over silica gel, Sephadex LH-20, MCI, and Rp C18. Structures of the isolates were determined by spectroscopic analysis as 10 coumarins: bergapten (1), xanthotoxin (2), isopimpinellin (3), isogosferal (4), imperatorin (5), meransin hydrate(6), isomeranzin(7), murrayone(8) , auraptenol(9), and osthol(10). In addition to compound 9, the others were isolated from the genus Leonurus for the first time. In the in vitro assay, compounds 4 and 8 significantly inhibited the abnormal increase of platelet aggregation induced by ADP. PMID:25850267

  9. 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.

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

    International Nuclear Information System (INIS)

    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 I2 (PGI2) released from endothelial cells in a quiescent state under physiological conditions

  11. 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.

  12. Mechanism of activation and functional role of protein kinase Ceta in human platelets.

    Science.gov (United States)

    Bynagari, Yamini S; Nagy, Bela; Tuluc, Florin; Bhavaraju, Kamala; Kim, Soochong; Vijayan, K Vinod; Kunapuli, Satya P

    2009-05-15

    The novel class of protein kinase C (nPKC) isoform eta is expressed in platelets, but not much is known about its activation and function. In this study, we investigated the mechanism of activation and functional implications of nPKCeta using pharmacological and gene knock-out approaches. nPKCeta was phosphorylated (at Thr-512) in a time- and concentration-dependent manner by 2MeSADP. Pretreatment of platelets with MRS-2179, a P2Y1 receptor antagonist, or YM-254890, a G(q) blocker, abolished 2MeSADP-induced phosphorylation of nPKCeta. Similarly, ADP failed to activate nPKCeta in platelets isolated from P2Y1 and G(q) knock-out mice. However, pretreatment of platelets with P2Y12 receptor antagonist, AR-C69331MX did not interfere with ADP-induced nPKCeta phosphorylation. In addition, when platelets were activated with 2MeSADP under stirring conditions, although nPKCeta was phosphorylated within 30 s by ADP receptors, it was also dephosphorylated by activated integrin alpha(IIb)beta3 mediated outside-in signaling. Moreover, in the presence of SC-57101, a alpha(IIb)beta3 receptor antagonist, nPKCeta dephosphorylation was inhibited. Furthermore, in murine platelets lacking PP1cgamma, a catalytic subunit of serine/threonine phosphatase, alpha(IIb)beta3 failed to dephosphorylate nPKCeta. Thus, we conclude that ADP activates nPKCeta via P2Y1 receptor and is subsequently dephosphorylated by PP1gamma phosphatase activated by alpha(IIb)beta3 integrin. In addition, pretreatment of platelets with eta-RACK antagonistic peptides, a specific inhibitor of nPKCeta, inhibited ADP-induced thromboxane generation. However, these peptides had no affect on ADP-induced aggregation when thromboxane generation was blocked. In summary, nPKCeta positively regulates agonist-induced thromboxane generation with no effects on platelet aggregation. PMID:19286657

  13. Dietary calcium attenuates platelet aggregation and intracellular Ca2+ mobilization in spontaneously hypertensive rats

    Science.gov (United States)

    Otsuka, K.; Watanabe, M.; Yue, Q.; McCarron, D. A.; Hatton, D.

    1997-01-01

    Spontaneously hypertensive rats (SHR) are known to be blood pressure sensitive to dietary calcium. The effects of dietary calcium on platelet aggregation and intracellular Ca2+ mobilization were assessed by turbidimetric methods and fura-2 methods, respectively, in washed platelets of SHR. Ca2+ ATPase activity was examined in aortic membrane fractions. Six weeks of dietary calcium supplementation attenuated the increase of systolic blood pressure (SBP 199 +/- 16 v 170 +/- 9 mm Hg, P ionomycin-induced intracellular calcium ([Ca2+]i) peak in the absence of external Ca2+, which reflects [Ca2+]i storage size, and thrombin-evoked [Ca2+]i release from [Ca2+]i storage were decreased by 2.0% Ca diet (472 +/- 55 v 370 +/- 23 nmol/L, P ionomycin-induced [Ca2+]i (r = 0.591, P = .0415), respectively. However, there was no significant effect of dietary calcium on Ca2+-ATPase activity in aortic membranes. These results suggest that dietary calcium supplementation had a beneficial effect on platelets of SHR by attenuating [Ca2+]i mobilization from [Ca2+]i storage. The hypotensive effect of dietary calcium might be associated with attenuated [Ca2+]i mobilization in SHR.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Exposure to acrolein by inhalation causes platelet activation

    International Nuclear Information System (INIS)

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

  20. 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

  1. 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.

  2. Effect of Vitamin C Supplementation on Platelet Aggregation and Serum Electrolytes Levels in Streptozotocin-Induced Diabetes Mellitus in Rats.

    Science.gov (United States)

    Owu, Daniel U; Nwokocha, Chukwuemeka R; Ikpi, Daniel E; Ogar, Emmanuel I

    2016-01-01

    Diabetes mellitus (DM) is a disease condition characterised by hyperglycemia; free radical and abnormalhaematological indices. Vitamin C can reduce free radical generation and ameliorate adverse conditions of diabetes mellitus.The aim of the present study is to investigate the effect of vitamin C on platelet aggregation and electrolyte levels in Type 1DM. Male Wistar rats were divided into four groups namely control, DM, DM +Vitamin C and Vitamin C groups. Rats weremade diabetic with a single dose of streptozotocin (65 mg/kg) intraperitoneally. Vitamin C was administered orally todiabetic and normal rats at 200 mg/kg body weight for 28 days. Blood samples were analyzed for hematological parameters,platelet aggregation, and serum electrolyte levels. Blood glucose in DM+ Vitamin C group (9.9 ± 1.8 mmol/L) wassignificantly reduced (pcontrol(4.4 ± 0.8 mmol/L). Haemoglobin (Hb) concentration in DM group (12 ± 0.1 g/dL) was significantly reduced (pcontrol groups (14 ± 0.24 g/dL) and significantly increased (pcontrol (59.49 ± 0.5fL). Platelet count in DM group (523± 8.5 x109/L) was significantly raised (pcontrol (356 ± 6.2 x109/L) and significantly reduced(pglucose level, platelet count, serumsodium/potassium ion ratio and inhibits platelet aggregation in streptozotocin-induced DM in rats. PMID:27574765

  3. Platelets

    Science.gov (United States)

    ... on the left. They are shaped like a plate, therefore their name. When platelets are stimulated by ... can occur, related to a restaurant or a contaminated food or water source. Shiga toxin can cause ...

  4. 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

  5. Inhibition of adenosine diphosphate-induced platelet aggregation by alpha-lipoic acid and dihydroquercetin in vitro

    Directory of Open Access Journals (Sweden)

    Ivan S Ivanov

    2014-01-01

    Full Text Available Objectives: To investigate the antiplatelet activity of alpha-lipoic acid (α-LA and dihydroquercetin (DHQ. Materials and Methods: Antiplatelet activity of the α-LA and DHQ was evaluated in rich platelet plasma of rat. The platelet aggregation was induced by adenosine diphosphate (ADP in concentration of 4 Χ 10 -5 Μ. Results: α-LA and DHQ inhibited platelet aggregation in concentration-dependent manner. The antiplatelet activity of α-LA was more pronounced than DHQ. DHQ also increased the antiplatelet activity of α-LA by 1.4 times. Conclusion: Combined simultaneous use of α-LA and DHQ possessed the high antiplatelet activity, and DHQ potentiated the activity of α-LA.

  6. The Heparin-Induced Thrombocytopenia and Thrombosis Syndrome: Treatment with Intraarterial Urokinase and Systemic Platelet Aggregation Inhibitors

    International Nuclear Information System (INIS)

    We report a case of the heparin-induced thrombocytopenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin

  7. BORON DEFICIENCY ALTERS PLATELET AGGREGATION DIFFERENTLY THAN REPLACING PALM OIL WITH CANOLA OIL IN THE DIET OF RATS

    Science.gov (United States)

    Support for the hypothesis that both boron (B) and long-chain n-3 fatty acids have membrane functions that affect each other would be finding that changes in B and n-3 fatty acid intakes affect a membrane-involved process such as platelet aggregation. Thus, female and male adult rats were fed diets...

  8. Hemolysate-mediated platelet aggregation: an additional risk mechanism contributing to thrombosis of continuous flow ventricular assist devices.

    Science.gov (United States)

    Tran, Phat L; Pietropaolo, Maria-Grazia; Valerio, Lorenzo; Brengle, William; Wong, Raymond K; Kazui, Toshinobu; Khalpey, Zain I; Redaelli, Alberto; Sheriff, Jawaad; Bluestein, Danny; Slepian, Marvin J

    2016-07-01

    Despite the clinical success and growth in the utilization of continuous flow ventricular assist devices (cfVADs) for the treatment of advanced heart failure, hemolysis and thrombosis remain major limitations. Inadequate and/or ineffective anticoagulation regimens, combined with high pump speed and non-physiological flow patterns, can result in hemolysis which often is accompanied by pump thrombosis. An unexpected increase in cfVADs thrombosis was reported by multiple major VAD implanting centers in 2014, highlighting the association of hemolysis and a rise in lactate dehydrogenase (LDH) presaging thrombotic events. It is well established that thrombotic complications arise from the abnormal shear stresses generated by cfVADs. What remains unknown is the link between cfVAD-associated hemolysis and pump thrombosis. Can hemolysis of red blood cells (RBCs) contribute to platelet aggregation, thereby, facilitating prothrombotic complications in cfVADs? Herein, we examine the effect of RBC-hemolysate and selected major constituents, i.e., lactate dehydrogenase (LDH) and plasma free hemoglobin (pHb) on platelet aggregation, utilizing electrical resistance aggregometry. Our hypothesis is that elements of RBCs, released as a result of shear-mediated hemolysis, will contribute to platelet aggregation. We show that RBC hemolysate and pHb, but not LDH, are direct contributors to platelet aggregation, posing an additional risk mechanism for cfVAD thrombosis. PMID:26590166

  9. Effects of taurine on plasma and liver lipids, erythrocyte ouabain sensitive Na efflux and platelet aggregation in Sprague Dawley rats

    OpenAIRE

    Park, In Sun; Kang, Young Hee; Kang, Jung Sook

    2007-01-01

    The effects of taurine on plasma and liver cholesterol, erythrocyte ouabain sensitive Na efflux and platelet aggregation were examined in Sprague Dawley rats fed control or 0.5% cholesterol with 0.2% cholate diet. Plasma and liver levels of total cholesterol were increased significantly (p

  10. Glucagon-Like Peptide 1 Receptor Activation Attenuates Platelet Aggregation and Thrombosis.

    Science.gov (United States)

    Cameron-Vendrig, Alison; Reheman, Adili; Siraj, M Ahsan; Xu, Xiaohong Ruby; Wang, Yiming; Lei, Xi; Afroze, Talat; Shikatani, Eric; El-Mounayri, Omar; Noyan, Hossein; Weissleder, Ralph; Ni, Heyu; Husain, Mansoor

    2016-06-01

    Short-term studies in subjects with diabetes receiving glucagon-like peptide 1 (GLP-1)-targeted therapies have suggested a reduced number of cardiovascular events. The mechanisms underlying this unexpectedly rapid effect are not known. We cloned full-length GLP-1 receptor (GLP-1R) mRNA from a human megakaryocyte cell line (MEG-01), and found expression levels of GLP-1Rs in MEG-01 cells to be higher than those in the human lung but lower than in the human pancreas. Incubation with GLP-1 and the GLP-1R agonist exenatide elicited a cAMP response in MEG-01 cells, and exenatide significantly inhibited thrombin-, ADP-, and collagen-induced platelet aggregation. Incubation with exenatide also inhibited thrombus formation under flow conditions in ex vivo perfusion chambers using human and mouse whole blood. In a mouse cremaster artery laser injury model, a single intravenous injection of exenatide inhibited thrombus formation in normoglycemic and hyperglycemic mice in vivo. Thrombus formation was greater in mice transplanted with bone marrow lacking a functional GLP-1R (Glp1r(-/-)), compared with those receiving wild-type bone marrow. Although antithrombotic effects of exenatide were partly lost in mice transplanted with bone marrow from Glp1r(-/-) mice, they were undetectable in mice with a genetic deficiency of endothelial nitric oxide synthase. The inhibition of platelet function and the prevention of thrombus formation by GLP-1R agonists represent potential mechanisms for reduced atherothrombotic events. PMID:26936963

  11. Gender and tachycardia: independent modulation of platelet reactivity in patients with atrial fibrillation

    Science.gov (United States)

    Procter, Nathan EK; Ball, Jocasta; Ngo, Doan TM; Isenberg, Jeffrey S; Hylek, Elaine M; Chirkov, Yuliy Y; Stewart, Simon; Horowitz, John D

    2016-01-01

    Background Female patients with atrial fibrillation (AF) experience increased risk of thromboembolism compared to males, an observation that is reflected by its inclusion in the CHA2DS2VASc score. New onset AF (often associated with tachycardia) also confers upon patients increased thromboembolic risk. The mechanisms underlying this risk are uncertain, but new onset AF is associated with profound impairment of platelet nitric oxide (NO) signalling. Given that cardiovascular responses to catecholamines are gender-dependent, and that the presence of tachycardia in new onset AF may represent a response to catecholaminergic stimulation, we explored the potential impact of gender and tachycardia on platelet aggregation and NO signalling. Methods Interactions were sought in 87 AF patients between the extent of adenosine diphosphate (ADP)-induced platelet aggregation, the anti-aggregatory effects of the NO donor, sodium nitroprusside, gender, and admission heart rate. The potential impact of platelet expression of thioredoxin-interacting protein (Txnip) was also evaluated. Results Analysis of covariance confirmed the presence of physiological antagonism between platelet ADP and NO responses [F (1, 74) = 12.212, P < 0.01], while female sex correlated with impaired NO responses independent of platelet aggregability [F (2, 74) = 8.313, P < 0.01]. Admission heart rate correlated directly with platelet aggregation (r = 0.235, P < 0.05), and inversely with NO response (r = −0.331, P < 0.01). Txnip expression varied neither with gender nor with heart rate. Conclusions These results indicate that gender and heart rate are independent determinants of platelet function. Prospective studies of the putative benefit of reversal of tachycardia on restoration of normal platelet function are therefore a priority. PMID:27103914

  12. Comparison of effect of locally available brands of clopidogrel on platelet aggregation in patients with coronary disease

    International Nuclear Information System (INIS)

    Background: Anticoagulant effect of clopidogrel is of utmost importance in coronary artery disease, especially in prevention of coronary stent thrombosis. Recently, many new local brands of clopidogrel have been launched, with unknown efficacy. This study was conducted with the aim to compare two locally prepared clopidogrel brands, in terms of the effect of a loading dose of 600 mg on inhibition of platelet aggregation in patients with coronary artery disease. Methods: This was a double blind randomised study. Sample population consisting of 35 patients, were admitted at Lady Reading Hospital, Peshawar, for the management of coronary artery disease. Baseline platelet aggregation of all these patients was measured. These patients were divided in two groups randomly. Group-A consisting of 18 patients was given brand 'A' clopidogrel 600 mg, while Group-B consisting of 17 patients was give brand 'B' of clopidogrel 600 mg. The platelet aggregation of both groups was then measured at baseline, and at 2, 4, and 6 hours after taking the loading dose of 600 mg. Results: Platelet aggregation time at baseline in Group-A was 2.61+- 2.28 sec. and in Group-B it was 2.24 +- 1.52 sec. (p=0.57). After 2 hours of clopidogrel administration in Group-A the platelet aggregation time was 1.44 +- 1.58 sec. and in Group-B it was 1.53 +- 1.107 sec. (p=0.85). Platelet aggregation time after 4 hours in Group-A was 0.28 +- 0.57 sec. and in Group-B 1.06 +- 1.03 sec. (p=0.009), and after 6 hours it was 0.00 +- 0.00 sec. in Group-A and in Group-B it was 0.59 +- 0.71 sec. (p=0.001). Conclusion: The two brands of clopidogrel had a significant difference in their effect on inhibition of platelet aggregation. Different brands of clopidogrel may not be equally effective. (author)

  13. Effect of acacia nilotica leaves extract on hyperglycaemia, lipid profile and platelet aggregation in streptozotocin induced diabetic rats

    International Nuclear Information System (INIS)

    To consider new hypoglycaemic, anti-hyperlipidaemic and anti-platelet aggregation sources, aqueous methanol extract of Acacia Nilotica (AN) leaves was investigated in streptozotocin induced diabetic rats. Methods: Diabetes mellitus was induced in 90 out of 120 male albino rats by administering 50 mg/Kg body weight (bw) streptozotocin intraperitoneal y, and was confirmed by measuring fasting blood glucose level >200 mg/dL on fourth post-induction day. The rats were equally divided into 4 groups, A (normal control), B (diabetic control), C (diabetics rats treated with plant extract) and group D (diabetics rats treated with glyburide). The rats of group C and D were given single dose of 300 mg/Kg bw, An extract, and 900 micro g/Kg bw glyburide respectively for 3 weeks. Blood glucose levels were measured by gluco meter, platelet aggregation by Dia Med method, beta-thrombo globulin and insulin by ELISA technique, and lipid components were measured by enzymatic calorimetric method. Results: Significant differences (p<0.05) were noticed in blood glucose, serum insulin, platelet aggregation and triglyceride levels in diabetic rats treated with AN extract and glyburide as compared to diabetic controlled rats. A significant difference (p<0.05) in beta-thrombo globulin and LDL levels was also noticed in rats treated with glyburide than the diabetic controlled rats. The levels of fasting blood glucose, beta-thrombo globulin and platelet aggregation were significantly reduced (p<0.05) in diabetic rats treated with glyburide than AN extract treated rats. Conclusions: Administration of AN leaves extract showed hypoglycaemic and anti-platelet aggregation activity in diabetic rats as that of glyburide. (author)

  14. Interaction of asialo von Willebrand factor with glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb/IIIa complex and mediates platelet aggregation

    International Nuclear Information System (INIS)

    Von Willebrand factor (vWF) is necessary for the initial attachment of platelets to exposed subendothelium, particularly under flow conditions like those prevailing in the microcirculation. Little is known about its possible participation in subsequent events leading to formation of platelet thrombi at sites of vascular injury. The authors addressed this question by studying the mechanisms by which desialylated vWF induces platelet aggregation in the absence of any other stimulus. Asialo vWF, unlike the native molecule, does not require ristocetin to interact with platelets. They have shown here that binding of asialo vWF to platelets was accompanied by release of dense granule content and subsequent ADP-dependent fibrinogen binding to receptors on the glycoprotein (GP) IIb/IIIa complex. The initial interaction of asialo vWF with platelets was mediated by GPIb, as shown by blocking obtained with monoclonal antibody. Inhibition of this initial interaction completely abolished platelet aggregation induced by asialo vWF. This, however, did not block asialo vWF binding to platelets, but rather inhibited subsequent fibrinogen binding induced by asialo vWF. Therefore, the latter process was also essential for platelet aggregation under the conditions described. This study shows that asialo, and possibly native, vWF acts as a platelet agonist after its binding to GPIb and induces aggregation through a pathway dependent on GPIIb/IIIa-related receptors

  15. The effect of the substituted amphetamines, 2.4-methylenedioxymethamphetamine (MDMA) and P-methoxyamphetamine (PMA), on platelet aggregation

    International Nuclear Information System (INIS)

    Full text: Illicit substituted amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA) and p-methoxyamphetamine (PMA) can cause severe toxicity. Disruption of normal coagulation mechanisms have been observed in most fatal cases. However, the precise mechanisms underlying these events are not clearly understood. MDMA and PMA are known to inhibit serotonin transporter function in the central nervous system (Daws et al 2000) and platelet serotonin transporter sites (Rudnick and Wall 1992). Serotonin is in high concentrations in platelets and activation of 5HT2 receptors on the platelet surface potentiates aggregation of platelets. Therefore, we postulated that MDMA and PMA may have effects on coagulation via inhibition of normal platelet function. Human citrated platelets were incubated in the presence of MDMA (43- 435μM) or PMA (49-498μM) and their aggregator y response to a critical dose of adenosine diphosphate (ADP) determined. These responses were compared to the serotonin reuptake inhibitor fluoxetine (13-130μM). All 3 compounds were found to inhibit platelet aggregation. The IC50s for % aggregation at 5 minutes were MDMA 197μM ± 63μM PMA 344μM ±76μM and fluoxetine 24μM ±1 1μM (n=4). The effect of these drugs on the uptake of 14C-5HT (0.9 μM /ml) into platelets was also determined and the IC50s observed were MDMA 62.3 μM ±11μM , PMA 24μM ±6μM and fluoxetine 2.5μM ± 0.6μM (n=4). The in vitro effects of MDMA and PMA on aggregation and uptake observed here are close to concentrations reported to have occurred in human fatalities. Therefore it is possible that direct effects of these drugs on coagulation mechanisms may contribute to the toxicity of these compounds. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  16. 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.

  17. 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

  18. A meta-analysis and genome-wide association study of platelet count and mean platelet volume in african americans.

    Directory of Open Access Journals (Sweden)

    Rehan Qayyum

    Full Text Available Several genetic variants associated with platelet count and mean platelet volume (MPV were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388 with p<5×10(-8 of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value: 6p22 (rs12526480, LRRC16A, p = 9.1×10(-9, 7q11 (rs13236689, CD36, p = 2.8×10(-9, 10q21 (rs7896518, JMJD1C, p = 2.3×10(-12, 11q13 (rs477895, BAD, p = 4.9×10(-8, and 20q13 (rs151361, SLMO2, p = 9.4×10(-9. Three of these loci (10q21, 11q13, and 20q13 were replicated in European Americans (N = 14,909 and one (11q13 in Hispanic Americans (N = 3,462. For MPV (N = 4,531, genetic variants in 3 regions were significant at p<5×10(-8, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24. Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic

  19. Inhibition of human platelet aggregation by a novel S-nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti-thrombotic therapy

    OpenAIRE

    Megson, Ian L; Sogo, Naoki; Mazzei, Francesca A; Butler, Anthony R.; Walton, John C; Webb, David J.

    2000-01-01

    S-Nitrosothiols are nitric oxide (NO) donor drugs that have been shown to inhibit platelet aggregation in platelet rich plasma (PRP) in vitro and to inhibit platelet activation in vivo. The aim of this study was to compare the platelet effects of a novel S-nitrosated glyco-amino acid, RIG200, with an established S-nitrosothiol, S-nitrosoglutathione (GSNO) in PRP, and to investigate the effects of cell-free haemoglobin and red blood cells on S-nitrosothiol-mediated inhibition of platelet aggre...

  20. 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

  1. The Role of the Midmolecular Peptides in the Blood Cell Aggregation in Acute Periods of a Burn Disease

    Directory of Open Access Journals (Sweden)

    Egorikhina M.N.

    2011-03-01

    Full Text Available The aim of the investigation is to study the effect of midmolecular peptide (MMP concentration on platelet and erythrocyte aggregation in severe burned patients. Materials and Methods. The investigation was carried out on 34 blood samples of healthy people and 30 blood samples of severe burned patients. There was determined the level of MMP, as well as that of creatinine, and urea. The “Amicon Ultra-4” microcentrifuge tubes were used to isolate MMP. Results. The level increase of average mass molecules isolated from the blood plasma of patients in an acute period of a burn disease has been stated to cause a progressive increase of platelet aggregation of healthy donors. The erythrocyte aggregation increase in such conditions is observed only in very high MMP concentrations. Creatinine and urea do not practically effect the ADP-induced platelet aggregation and the erythrocyte aggregation of healthy donors, and even decrease spontaneous thrombocyte aggregation in very high concentrations occur in an acute renal insufficiency. Conclusion. One of the reasons of platelet aggregation decrease under the influence of chemosorption in a burn disease can be the decrease of the MMP concentration in response to chemosorption.

  2. 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.

  3. Aggregation of human platelets by endotoxic glycolipid-bearing Salmonella minnesota Re595 is prevented by synthetic peptide analogs of cell adhesion sites of fibrinogen and fibronectin

    International Nuclear Information System (INIS)

    Thrombocytopenia often accompanies sepsis due to endotoxin producing gram-negative bacteria. The authors have observed that mutant Re595 of S. minnesota induced aggregation of human platelets separated from plasma fibrinogen (Theta) and other proteins. This aggregation is dependent on ADP secreted from storage granules in response to mutant Re595. Platelet aggregation induced by mutant Re595 was prevented by simultaneously added EDTA and EGTA (5mM), whereas secretion of 14C-serotonin was maintained. Preincubation of platelets with chelators (1 hr, 370C), known to dissociate irreversibly the platelet membrane glycoprotein IIb x IIIa complex, abolished aggregation while serotonin secretion was decreased by only one fourth. Since the GPIIb x IIIa complex constitutes the receptor for Theta, its role was examined using synthetic peptide analogs of sites on gamma and alpha chains of Theta. Gamma 400-411 (225 μM) inhibited platelet aggregation induced by mutant Re595 while serotonin secretion was unaffected. Alpha 572-575 (RGDS; 100 μM), analogous to cell adhesion site of fibronectin, also prevented aggregation induced by mutant Re595. Thus, mutant Re595 causes platelet aggregation which is divalent cation-dependent and proceeds via receptor pathway for secreted adhesive macromolecules

  4. Concord grape juice attenuates platelet aggregation, serum cholesterol and development of atheroma in hypercholesterolemic rabbits.

    Science.gov (United States)

    Shanmuganayagam, Dhanansayan; Warner, Thomas F; Krueger, Christian G; Reed, Jess D; Folts, John D

    2007-01-01

    Intake of Concord grape juice (CGJ), rich in polyphenolics, inhibits platelet aggregation (PA), a risk factor for cardiovascular disease (CVD), in normocholesterolemic animals and humans. It is unclear whether CGJ can attenuate hypercholesterolemia-enhanced PA. The effects of daily CGJ consumption on hypercholesterolemia-enhanced PA and the development of atherosclerosis were investigated. Two groups of rabbits (Control and Treated; n=10 each) were fed a hypercholesterolemic diet for 48 days. Treated group then received supplemental CGJ (225mL/day) while Control group received supplemental iso-caloric sugar water for 48 days. Collagen-, collagen+epinephrine- and phorbol-12-myristate-13-acetate-induced whole blood PA responses were measured on Days 0, 48 and 96; total serum cholesterol and blood pressure were also measured. The development of aortic atheroma was quantified at the end. Both groups showed significant increases in PA and serum cholesterol at Day 48. However, at Day 96, Treated group showed significantly lower PA and development of atheroma (30.7+/-3.9% lower (pCGJ attenuates hypercholesterolemia-enhanced PA, blood pressure, total serum cholesterol and development of atheroma in rabbits. PMID:16780846

  5. ACE and platelet aggregation inhibitors from Tamarix hohenackeri Bunge (host plant of Herba Cistanches) growing in Xinjiang

    OpenAIRE

    Xing, Yachao; Liao, Jing; Tang, Yingzhan; Peng ZHANG; Tan, Chengyu; Ni, Hui; Wu, Xueqin; Li, Ning; Jia, Xiaoguang

    2014-01-01

    Background: Tamarix hohenackeri Bunge is a salt cedar that grows widespread in the desert mountains in Xinjiang. T. hohenackeri has not been investigated earlier, although there are many reports of phytochemical work on other Tamarix species. Materials and Methods: To find out natural angiotensin-converting enzyme (ACE) inhibitor and platelet aggregation inhibitors, the bioactive extract (ethyl acetate [EtOAc] fraction) from the dried aerial parts of T. hohenackeri were investigated. The acti...

  6. Role of cytoplasmic and releasable ADP in platelet aggregation induced by laminar shear stress

    International Nuclear Information System (INIS)

    We examined the extent of lytic and sublytic platelet injury after exposure of platelets to shear stress and the role in shear-induced PAG of ADP liberated from platelets as a result of shear-induced platelet dense body release and/or platelet damage. Platelets in C-PRP or TAS were subjected to well-defined, laminar shear stress in a rotational viscometer, and PAG (loss of single, nonaggregated platelets), 14C-serotonin release, and loss from platelets of LDH and 51Cr were determined. Increased PAG with increasing shear stresses was associated with progressive loss of LDH and 51Cr. Loss of 51Cr was consistently in excess of that of LDH, indicating sublytic platelet injury, which was confirmed by electron microscopy. At the lowest shear stress used (50 dynes/cm2), PAG in C-PRP was observed in the absence of detectable loss of 51Cr or LDH. When platelets in TAS were sheared in the presence of CP/CPK, an enzyme system capable of removing extracellular ADP, PAG was only partially (approximately 40%) inhibited. However, when platelets were preincubated with CP/CPK and ATP (to saturate platelet ADP receptors), shear-induced PAG was almost completely suppressed. Similar results were obtained with PAG induced by collagen in the aggregometer. The findings indicate that (1) shear-induced PAG in this system may occur without measurable lytic or sublytic platelet damage and (2) ADP liberated from platelets as a result of shear-induced release or damage may represent the major if not sole mediator of shear-induced PAG

  7. The saliva proteome of the blood-feeding insect Triatoma infestans is rich in platelet-aggregation inhibitors

    Science.gov (United States)

    Charneau, Sébastien; Junqueira, Magno; Costa, Camila M.; Pires, Daniele L.; Fernandes, Ellen S.; Bussacos, Ana C.; Sousa, Marcelo V.; Ricart, Carlos André O.; Shevchenko, Andrej; Teixeira, Antonio R. L.

    2007-12-01

    The saliva of the bloodsucking bug Triatoma infestans vector of Chagas disease contains an anti-hemostatic molecular cocktail that prevents coagulation, vasoconstriction and platelet aggregation in a vertebrate prey. In order to characterize T. infestans saliva proteome, we separated the secreted saliva by two-dimensional gel electrophoresis (2-DE). More than 200 salivary proteins were detected on the 2-DE map, mainly in the alkaline region. By nanoLC-MS/MS analysis using a LTQ-Orbitrap equipment followed by a combination of conventional and sequence-similarity searches, we identified 58 main protein spots. Most of such proteins possess potential blood-feeding associated functions, particularly anti-platelet aggregation proteins belonging to lipocalin and apyrase families. The saliva protein composition indicates a highly specific molecular mechanism of early response to platelet aggregation. This first proteome analysis of the T. infestans secreted saliva provides a basis for a better understanding of this fluid protein composition highly directed to counterpart hemostasis of the prey, thus promoting the bug's blood-feeding.

  8. Effect of GABA derivatives on the rate of thrombus formation, platelet aggregation, and plasma coagulation capacity in rats with experimental gestosis.

    Science.gov (United States)

    Tyurenkov, I N; Perfilova, V N; Karamysheva, V I; Reznikova, L B; Mokrousov, I S; Mikhailova, L I; Berestovitskaya, V M; Vasil'eva, O S

    2014-12-01

    Experimental gestosis induced by replacement of drinking water with 1.8% NaCl promoted hypercoagulation, increased the rate and degree of platelet aggregation, and reduced clotting time in pregnant females. GABA derivatives, compounds RGPU-151, RGPU-152, and phenibut normalized parameters of hemostasis and platelet aggregation and the rate of thrombus formation in the animals. The efficiency of the test substances did not significantly differ from that of the reference drug sulodexide. PMID:25432276

  9. Naringin administration inhibits platelet aggregation and release by reducing blood cholesterol levels and the cytosolic free calcium concentration in hyperlipidemic rabbits

    OpenAIRE

    Xiao, Yang; LI, LAI-LAI; Guo, Jing-Jing; XU, WEN-PING; Wang, Yan-Yan; Wang, Yi

    2014-01-01

    This study investigated the effects of naringin on platelet aggregation and release in hyperlipidemic rabbits, and the underlying mechanisms. The safety of naringin was also investigated. The rabbits were orally administered 60, 30 or 15 mg/kg of naringin once a day for 14 days after being fed a high fat/cholesterol diet for four weeks. Following the two weeks of drug administration, the degree of platelet aggregation induced by arachidonic acid, adenosine diphosphate and collagen was signifi...

  10. Acetyl eugenol, a component of oil of cloves (Syzygium aromaticum L.) inhibits aggregation and alters arachidonic acid metabolism in human blood platelets.

    Science.gov (United States)

    Srivastava, K C; Malhotra, N

    1991-01-01

    In continuation of our studies with the oil of cloves--a common kitchen spice and a crude drug for home medicine--we have isolated yet another active component identified as acetyl eugenol (AE); the earlier reported active component being eugenol. The isolated material (IM) was found to be a potent platelet inhibitor; IM abolished arachidonate (AA)-induced aggregation at ca. 12 microM, a concentration needed to abolish the second phase of adrenaline-induced aggregation. Chemically synthesized acetyl eugenol showed similar effects on AA- and adrenaline-induced aggregation. A dose-dependent inhibition of collagen-induced aggregation was also observed. AE did not inhibit either calcium ionophore A23187- or thrombin-induced aggregation. Studies on aggregation and ATP release were done using whole blood (WB). AA-induced aggregation in WB was abolished at 3 micrograms/ml (14.6 microM) which persisted even after doubling the concentration of AA. ATP release was inhibited. Inhibition of aggregation appeared to be mediated by a combination of two effects: reduced formation of thromboxane and increased generation of 12-lipoxygenase product (12-HPETE). These effects were observed by exposing washed platelets to (14C)AA or by stimulating AA-labelled platelets with ionophore A23187. Acetyl eugenol inhibited (14C)TxB2 formation in AA-labelled platelets on stimulation with thrombin. AE showed no effect on the incorporation of AA into platelet phospholipids. PMID:2011614

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

    Directory of Open Access Journals (Sweden)

    Khan N

    2015-07-01

    Full Text Available Nadia Khan,1,2 Ahsana Dar Farooq,1 Bassem Sadek21Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan; 2Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesAbstract: 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 Ca2+ channels, Gq/PLC, and MAPK signaling

  12. Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis.

    OpenAIRE

    Le, Vuong Ba; Schneider, Jochen; Boergeling, Yvonne; Berri, Fatma; Ducatez, Mariette; GUERIN, Jean-Luc; Adrian, Iris; Errazuriz-Cerda, Elisabeth; frasquilho, sonia; Antunes, Laurent; Lina, Bruno; Bordet, Jean-Claude; Jandrot-Perrus, Martine; Ludwig, Stephan; Riteau, Beatrice

    2015-01-01

    RATIONALE: The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown. OBJECTIVES: To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza. METHODS: We used targeted gene deletion approaches and pharmacologic interventions to investigate the role of platelets during influenza v...

  13. 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.

  14. A synthetic peptide derived from the sequence of a type I collagen receptor inhibits type I collagen-mediated platelet aggregation.

    OpenAIRE

    Chiang, T M; Kang, A H

    1997-01-01

    A synthetic peptide-1, an 18 amino acid residue peptide derived from a hydrophilic domain of a cloned platelet type I collagen receptor, was used to study the role of the receptor on types I and III collagen-induced platelet aggregation and the release of ATP. The peptide inhibits the type I, but not the type III, collagen-induced platelet aggregation and the release of ATP in a dose-dependent manner. The [125I]peptide-1 specifically binds to type I collagen-coated microtiter wells in a dose-...

  15. Chemical synthesis of echistatin, a potent inhibitor of platelet aggregation from Echis carinatus: synthesis and biological activity of selected analogs.

    Science.gov (United States)

    Garsky, V M; Lumma, P K; Freidinger, R M; Pitzenberger, S M; Randall, W C; Veber, D F; Gould, R J; Friedman, P A

    1989-06-01

    Echistatin, a polypeptide from the venom of the saw-scaled viper, Echis carinatus, containing 49 amino acids and 4 cystine bridges was synthesized by solid-phase methodology in 4% yield. In the final step, air oxidation of the octahydroderivative was found to be optimal at pH 8. The synthetic product was shown to be physically and biologically indistinguishable from native material. It inhibits fibrinogen-dependent platelet aggregation stimulated by ADP with IC50 = 3.3 x 10(-8) M and also prevents aggregation initiated by thrombin, epinephrine, collagen, or platelet-activating factor. Reduction of purified synthetic echistatin to octahydroechistatin with dithiothreitol followed by air oxidation regenerated homogeneous echistatin in quantitative yield. This highly specific refolding strongly suggests that the linear sequence of octahydroechistatin contains all of the information that is required for the proper folding of the peptide. The sequence Arg24-Gly-Asp of echistatin occurs also in adhesive glycoproteins that bind to the platelet fibrinogen receptor--a heterodimeric complex composed of glycoproteins IIb and IIIa. In an effort to evaluate the role of this putative binding site we have synthesized analogs of echistatin with substitution of Arg-24. Replacement with ornithine-24 (Orn-24) resulted in an analog having a platelet aggregation inhibitory activity with IC50 = 1.05 x 10(-7) M. Substitution with Ala-24 gave IC50 = 6.1 x 10(-7) M. The inhibitory activity of the corresponding short sequence analogs Arg-Gly-Asp-Phe (IC50 = 6 x 10(-6) M), Orn-Gly-Asp-Phe (IC50 = 1.3 x 10(-4) M), and Ala-Gly-Asp-Phe (IC50 = 5.0 x 10(-4) M) was also determined. These results suggest that arginine plays a more important role in the binding of the tetrapeptide than in that of echistatin. PMID:2726764

  16. 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.

  17. The antidepressant 5-HT2A receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function.

    Directory of Open Access Journals (Sweden)

    Olivia A Lin

    Full Text Available There is considerable interest in defining new agents or targets for antithrombotic purposes. The 5-HT2A receptor is a G-protein coupled receptor (GPCR expressed on many cell types, and a known therapeutic target for many disease states. This serotonin receptor is also known to regulate platelet function. Thus, in our FDA-approved drug repurposing efforts, we investigated the antiplatelet activity of cyproheptadine and pizotifen, two antidepressant 5-HT2A Receptor antagonists. Our results revealed that cyproheptadine and pizotifen reversed serotonin-enhanced ADP-induced platelet aggregation in vitro and ex vivo. And the inhibitory effects of these two agents were found to be similar to that of EMD 281014, a 5-HT2A Receptor antagonist under development. In separate experiments, our studies revealed that these 5-HT2A receptor antagonists have the capacity to reduce serotonin-enhanced ADP-induced elevation in intracellular calcium levels and tyrosine phosphorylation. Using flow cytometry, we also observed that cyproheptadine, pizotifen, and EMD 281014 inhibited serotonin-enhanced ADP-induced phosphatidylserine (PS exposure, P-selectin expression, and glycoprotein IIb-IIIa activation. Furthermore, using a carotid artery thrombosis model, these agents prolonged the time for thrombotic occlusion in mice in vivo. Finally, the tail-bleeding time was investigated to assess the effect of cyproheptadine and pizotifen on hemostasis. Our findings indicated prolonged bleeding time in both cyproheptadine- and pizotifen-treated mice. Notably, the increases in occlusion and bleeding times associated with these two agents were comparable to that of EMD 281014, and to clopidogrel, a commonly used antiplatelet drug, again, in a fashion comparable to clopidogrel and EMD 281014. Collectively, our data indicate that the antidepressant 5-HT2A antagonists, cyproheptadine and pizotifen do exert antiplatelet and thromboprotective effects, but similar to clopidogrel and

  18. CYP-independent inhibition of platelet aggregation in rabbits by a mixed disulfide conjugate of clopidogrel.

    Science.gov (United States)

    Zhang, H; Lauver, D A; Hollenberg, P F

    2014-12-01

    Dual antiplatelet therapy with clopidogrel and aspirin has been the standard of care in the United States for patients with acute coronary syndromes (ACS) and/or undergoing percutaneous coronary interventions (PCI). However, the effectiveness of clopidogrel varies significantly among different sub-populations due to inter-individual variability. In this study we examined the antiplatelet potential of a novel mixed disulfide conjugate of clopidogrel with the aim to overcome the inter-individual variability. In the metabolic studies using human liver microsomes and cDNA-expressed P450s, we confirmed that multiple P450s are involved in the bioactivation of 2-oxoclopidogrel to H4, one of the diastereomers of the pharmacologically active metabolite (AM) possessing antiplatelet activity. Results from kinetic studies demonstrated that 2C19 is the most active in converting 2-oxoclopidogrel to H4 with a catalytic efficiency of 0.027 µM⁻¹min⁻¹ in the reconstituted system. On the basis of this finding, we were able to biosynthesise the conjugate of clopidogrel with 3-nitropyridine-2-thiol, referred to as clopNPT, and examined its antiplatelet activity in male New Zealand white rabbits. After administration as intravenous bolus at 2 mg/kg, the clopNPT conjugate was rapidly converted to the AM leading to the inhibition of platelet aggregation (IPA). Analyses of the blood samples drawn at various time points showed that intravenous administration of clopNPT led to ~70% IPA within 1 hour and the IPA persisted for more than 3 hours. Since the antiplatelet activity of clopNPT does not require bioactivation by P450s, the mixed disulfide conjugate of clopidogrel has the potential to overcome the inter-individual variability in clopidogrel therapy. PMID:25230737

  19. 不稳定性心绞痛患者心理社会因素与血小板聚集功能关系的研究%Relationship between Psychosocial Factors end Platelet Aggregation Function inPatients with Unstable Angina Pectoris

    Institute of Scientific and Technical Information of China (English)

    夏大胜; 刘书坤; 高陆; 曹燕然; 菅练

    2001-01-01

    目的:探讨不稳定性心绞痛(UAP)患者心理社会因素与血小板聚集功能的关系。方法:采用6个心理量表对46例UAP患者和46例健康人进行评定,并测定ADP诱导的血小板聚集率。结果:UAP组负性生活事件刺激量、消极应对、CH、焦虑和抑郁积分及血小板聚集率均高于对照组(均P<0.01),社会支持总分和积极应对分低于对照组(均P<0.01),UAP组A型行为、焦虑及抑郁分别占73.91%、82.6%和71.4%,高于对照组36.96%、34.8%和21.7%(均P<0.01)。UAP患者焦虑、抑郁程度与负性生活事件刺激量、消极应对分、CH分及血小板聚集率正相关(P<0.05或P<0.01),与社会支持总分负相关(均P<0.05),血小板聚集率与负性生活事件刺激量、CH分亦显著正相关(均P<0.01)。结论:UAP患者由于处于心理应激状态,表现焦虑、抑郁情绪障碍,血小板聚集功能增强,对疾病的发展和预后可能产生不利影响。%Objective:To explore the relationship between psychosocial factors and platelet aggregation function in patients withunstable angina pectoris(UAP). Methods:Forty-six UAP patients and 46 healthy subjects were evaluated with 6 psychologi-cal scales,and their adenosine diphosphate(ADP)-induced platelet aggregation function was determined. Results: The scoresof negative life event stimuli,negative coping,CH, anxiety, depression and the rate of platelet aggregation function in UAPgroup were significantly higher than controls, whereas the scores of total social support and positive coping were markedlylower than controls(all P<0.01). The prevalence of type A behavior, anxiety and depression in UAP group(73.91%,82.60% and 71.40% respectively)was higher than controls(36.96% ,34.80% and 21.70%respectively)(all P<0.01).The scores of anxiety or depression in UAP group had a positive correlation with the scores of negative life event stimuli,negative coping

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

    International Nuclear Information System (INIS)

    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. (Author)

  1. Selective and rapid monitoring of dual platelet inhibition by aspirin and P2Y12 antagonists by using multiple electrode aggregometry

    Directory of Open Access Journals (Sweden)

    Lorenz Reinhard

    2010-05-01

    Full Text Available Abstract Background Poor platelet inhibition by aspirin or clopidogrel has been associated with adverse outcomes in patients with cardiovascular diseases. A reliable and facile assay to measure platelet inhibition after treatment with aspirin and a P2Y12 antagonist is lacking. Multiple electrode aggregometry (MEA, which is being increasingly used in clinical studies, is sensitive to platelet inhibition by aspirin and clopidogrel, but a critical evaluation of MEA monitoring of dual anti-platelet therapy with aspirin and P2Y12 antagonists is missing. Design and Methods By performing in vitro and ex vivo experiments, we evaluated in healthy subjects the feasibility of using MEA to monitor platelet inhibition of P2Y12 antagonists (clopidogrel in vivo, cangrelor in vitro and aspirin (100 mg per day in vivo, and 1 mM or 5.4 mM in vitro alone, and in combination. Statistical analyses were performed by the Mann-Whitney rank sum test, student' t-test, analysis of variance followed by the Holm-Sidak test, where appropriate. Results ADP-induced platelet aggregation in hirudin-anticoagulated blood was inhibited by 99.3 ± 1.4% by in vitro addition of cangrelor (100 nM; p 95% and 100 ± 3.2%, respectively (p in vitro or ex vivo. Oral intake of clopidogrel did not significantly reduce AA-induced aggregation, but P2Y12 blockade by cangrelor (100 nM in vitro diminished AA-stimulated aggregation by 53 ± 26% (p Conclusions Selective platelet inhibition by aspirin and P2Y12 antagonists alone and in combination can be rapidly measured by MEA. We suggest that dual anti-platelet therapy with these two types of anti-platelet drugs can be optimized individually by measuring platelet responsiveness to ADP and AA with MEA before and after drug intake.

  2. Platelet-collagen interaction: inhibition by a monoclonal antibody raised against collagen receptor

    International Nuclear Information System (INIS)

    The authors have previously reported that polyclonal antibody raised against the purified platelet collagen receptor cross reacted with glycoprotein IIb-IIIa complex of platelets. In order to study the receptor function further, the authors prepared a monoclonal antibody to the collagen receptor (65K). Platelet collagen receptor was purified as described previously by the authors. Mice were immunized by injection of purified 65K protein emulsified in complete Freund's adjuvant, and hybridomas were obtained from the fusion of spleen cells of immunized mice with myeloma cells (SP 2/0). The assay for antibody was performed with enzyme-linked immunosorbent assay. The hybridoma cells producing specific anti-65K protein were subcloned and the subcloned cells were injected into peritoneal cavity of Pristane-Primed mice. Immunoglobulin G(IgG) was isolated from ascitic fluids by an Affigel Blue chromatography. The Fab' fragments were isolated from papain digested IgG followed by an Affigel Blue chromatography. Immunoblot experiments using the monoclonal IgG of solubilized platelet membrane proteins following NaDodSO4-polyacrylamide gel electrophoresis showed that the monoclonal IgG reacted with the antigen specifically. It did not react with glycoprotein IIb-IIIa. The isolated IgG and Fab' fragments inhibited competitively the binding of radiolabelled α1(I) to washed platelets and soluble collagen- as well as fibrillar collagen-induced but not ADP-induced platelet aggregation. This indicates that collagen-induced platelet aggregation is mediated through interaction of collagen with 65K platelet receptor

  3. Platelet-collagen interaction: inhibition by a monoclonal antibody raised against collagen receptor

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, T.; Jin, A.; Kang, A.

    1986-05-01

    The authors have previously reported that polyclonal antibody raised against the purified platelet collagen receptor cross reacted with glycoprotein IIb-IIIa complex of platelets. In order to study the receptor function further, the authors prepared a monoclonal antibody to the collagen receptor (65K). Platelet collagen receptor was purified as described previously by the authors. Mice were immunized by injection of purified 65K protein emulsified in complete Freund's adjuvant, and hybridomas were obtained from the fusion of spleen cells of immunized mice with myeloma cells (SP 2/0). The assay for antibody was performed with enzyme-linked immunosorbent assay. The hybridoma cells producing specific anti-65K protein were subcloned and the subcloned cells were injected into peritoneal cavity of Pristane-Primed mice. Immunoglobulin G(IgG) was isolated from ascitic fluids by an Affigel Blue chromatography. The Fab' fragments were isolated from papain digested IgG followed by an Affigel Blue chromatography. Immunoblot experiments using the monoclonal IgG of solubilized platelet membrane proteins following NaDodSO/sub 4/-polyacrylamide gel electrophoresis showed that the monoclonal IgG reacted with the antigen specifically. It did not react with glycoprotein IIb-IIIa. The isolated IgG and Fab' fragments inhibited competitively the binding of radiolabelled ..cap alpha..1(I) to washed platelets and soluble collagen- as well as fibrillar collagen-induced but not ADP-induced platelet aggregation. This indicates that collagen-induced platelet aggregation is mediated through interaction of collagen with 65K platelet receptor.

  4. Polymers for the rapid and effective activation and aggregation of platelets.

    Science.gov (United States)

    Hansen, Anne; McMillan, Loraine; Morrison, Alex; Petrik, Juraj; Bradley, Mark

    2011-10-01

    Platelets are responsible for plugging sites of vascular injury, where upon activation they spread out and become cross-linked, preventing further blood loss. It is desirable to control the activation process on demand for applications such as the rapid staunching of blood flow following trauma. Polymers are the material of choice in many biological areas, with physical properties that allow control of morphology as well as ease of functionalisation and production. Herein, polymer microarrays were used to screen a complex human fluid (platelet rich plasma) to identify polyacrylates that could be used to modulate platelet activation. Several polymers were identified which rapidly activated platelets as determined by CD61P binding and subsequent confirmation by scanning electron microcopy analysis. This approach enabled a direct comparison between the natural agonist collagen and synthetic polymers with respect to the activation status of the platelets as well as the number of bound platelets. Further investigations under physiological flow demonstrated that the static microarray experiments gave viable candidates for potential medical applications while specific protein binding to the polymers was identified as a possible mode of action. The approach demonstrates the ability of polymer microarrays to identify new polymers for specific biological activation events and in this case allowed the identification of materials that allowed higher levels of platelets to bind in advanced activation states than the natural standard collagen in static and flow studies. PMID:21719101

  5. A Decreased Responsiveness of Platelet to Nitric Oxide in Cholesterol-Fed Rabbits

    Institute of Scientific and Technical Information of China (English)

    SUNJing; ZHANGAi-xia; LUOChun-xia; WANGWei; SUNYong-jun; ZHUDong-ya

    2004-01-01

    To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis. Sermn NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol. The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Resu/ts.Cholesterol diet significantly increased sermn levels of cholesterol and LDL, caused a remarkable platelet hyperaggregability, and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination. The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNIP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclexosis. :The present study suggests that the endothelial dysfunction caused by enhanced sermn cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.

  6. Comparison of indium 111 oxine-labeled platelet aggregation between sutured and argon laser-assisted vascular anastomoses

    International Nuclear Information System (INIS)

    The thrombogenicity of argon laser-assisted vascular anastomoses (LAVAs) was compared with that of sutured vascular anastomoses (SVAs) by measurement of platelet aggregation at the site of repair in a canine model. Sequential 1 cm longitudinal carotid and femoral arteriotomies (n = 80) or jugular and femoral phlebotomies (n = 80) were performed, with each vessel having two tandem, randomly positioned arteriotomies or phlebotomies separated by a 4 cm length of intact vessel. One incision was repaired by SVA with continuous 6-0 polypropylene sutures and the other by argon LAVA. For the laser fusions, argon laser energy was applied to the adventitial surface of the vessel with a 300 micron fiberoptic probe with 0.5 W power, 1100 joules per square centimeter energy fluence, and 150 second exposure per 1 cm length. The arterial and venous segments of SVAs and LAVAs and an equivalent length of normal vessel were harvested at 48 hours (n = 16, 16, 16), 2 weeks (n = 12, 12, 12), and 4 weeks (n = 12, 12, 12). Autologous indium 111 oxine-labeled platelets were injected intravenously 48 hours before removal of the vascular repairs and the radioactivity of the specimens was determined on removal with a NaI (T1) well-type scintillation counter. Anastomotic platelet adherence index (APAI) was calculated as the ratio of emissions of SVA or LAVA to normal reference vessel

  7. Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in human blood stimulated by atherosclerotic plaque

    OpenAIRE

    Khandoga Anna L; Pandey Dharmendra; Dwivedi Suman; Brandl Richard; Siess Wolfgang

    2010-01-01

    Abstract Background Platelet activation requires rapid remodeling of the actin cytoskeleton which is regulated by small GTP-binding proteins. By using the Rac1-specific inhibitor NSC23766, we have recently found that Rac1 is a central component of a signaling pathway that regulates dephosphorylation and activation of the actin-dynamising protein cofilin, dense and α-granule secretion, and subsequent aggregation of thrombin-stimulated washed platelets. Objectives To study whether NSC23766 inhi...

  8. Enhanced expression of Aggrus (T1alpha/podoplanin), a platelet-aggregation-inducing factor in lung squamous cell carcinoma.

    Science.gov (United States)

    Kato, Yukinari; Kaneko, Mika; Sata, Makoto; Fujita, Naoya; Tsuruo, Takashi; Osawa, Motoki

    2005-01-01

    Aggrus (T1alpha/podoplanin, known as a specific marker for type I alveolar cells or lymphatic endothelial cells) is a transmembrane sialoglycoprotein that aggregates platelets. Previously, we showed that upregulated expression of Aggrus occurs in colorectal tumors or testicular tumors and could be associated with platelet-aggregating activity and metastatic ability. In testicular tumors, Aggrus is specifically expressed in seminoma. The present study investigates Aggrus expression in human primary lung cancer tissues of different types. Microarray analysis demonstrated that aggrus was significantly expressed in squamous cell carcinoma (10/15; 66.7%). Immunohistochemical analysis also showed that the incidence of positive staining in sections of squamous cell carcinoma (7/8; 87.5%) was higher than that in adenocarcinoma (2/13; 15.4%). Furthermore, Aggrus expression was detected in a squamous cell carcinoma cell line, NCI-H226, by real-time PCR. These findings indicated that overexpression of Aggrus occurred in squamous cell carcinoma of the lung. Therefore, Aggrus could be a useful diagnostic marker for squamous cell carcinoma of the lung. PMID:16006773

  9. Significance of detection of the monocyte CD14+CD16+ subsets and monocyte-platelet aggregates in patients with cerebral infarction by FCM

    International Nuclear Information System (INIS)

    Objective: To investigate the mononuclear cell subsets distribution and monocyte-platelet aggregates of the peripheral blood in patients with cerebral infarction and its clinical significance. Methods: In 48 patients with cerebral infarction and 31 normal controls, the expression levels of CD14, CD16, CD41 were measured by flow cytometry. Results: The expression levels of CD14, Cr16 and CD41 on monocyte in group of cerebral infarction patients were significant difference than those in normal control (P+CD16+ subsets and the monocyte-platelet aggregates (PMAs) were helpful for the early diagnosis in patients with cerebral infarction. (authors)

  10. 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

    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...

  11. Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats

    OpenAIRE

    Eunseop Yeom; Hyeokjun Byeon; Sang Joon Lee

    2016-01-01

    Diabetes mellitus with abnormal glucose concentration is associated with changes in hemorheological properties, endothelial function, and platelets hyperactivity. Disturbances may significantly be responsible for diabetes-related vascular complications. In this study, hemorheological and hemodynamic properties were measured according to diabetic duration after streptozotocin treatment in rats. For ex vivo measurements, an extracorporeal model was adopted. Flow rate and blood viscosity were me...

  12. 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.

  13. Effect of a New Antioxidant Enoxifol on Platelet Aggregation and Blood Rheological Properties in Rats with Experimental Diabetes Mellitus.

    Science.gov (United States)

    Kucheryavenko, A F; Spasov, A A; Anisimova, V A

    2016-04-01

    Effect of a new antioxidant enoxifol exhibiting antiplatelet activity in vitro and in vivo on hemostasis parameters was assessed in laboratory rats with experimental diabetes mellitus. Gliclazide, a hypoglycemic agent with antiplatelet properties, and pentoxifylline, a preparation improving blood rheology, were used as the reference drugs. Enoxifol produced a pronounced inhibitory effect on platelet aggregation in rats with experimental diabetes comparable to the effect of gliclazide and decreased blood viscosity thus demonstrating a significant effect comparable to that of pentoxifylline. In view of the fact that oxidative stress is a pathogenetic components of vascular complications in diabetes, it can be assumed that improvement of hemostasis parameters under the effect of enoxifol is determined by its antiplatelet and antioxidant activities. PMID:27165061

  14. 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

    -pretreated patients. BACKGROUND: Clopidogrel, in combination with aspirin, reduces cardiovascular events in patients with acute coronary syndromes (ACS). However, patients with poor inhibition of platelet aggregation with clopidogrel may be less well protected. AZD6140 is a reversible oral P2Y(12) receptor antagonist...

  15. Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Effects on platelet aggregation and thromboxane formation.

    Science.gov (United States)

    Lorenz, R L; Schacky, C V; Weber, M; Meister, W; Kotzur, J; Reichardt, B; Theisen, K; Weber, P C

    1984-06-01

    Prevention of aortocoronary bypass occlusion by aspirin (ASA, 1 X 100 mg per day) was studied in a prospective double-blind trial of 83 patients. 60 (72%) were randomly allocated to ASA or placebo starting 24 h after operation. 90% of grafts in the ASA group and 68% in the placebo group were patent at four months. At least one anastomosis was occluded in 62% of the patients on placebo and in 27% of those on aspirin. Ventricular arrhythmias increased after surgery in more patients on placebo (12/18) than in patients on ASA (5/17). Platelet thromboxane formation on collagen tested before operation was significantly higher in patients in whom bypass occlusion developed (occlusion: 40 +/- 19, no occlusion: 25 +/- 13 ng/ml). A 100 mg dose of ASA per day effectively blocked platelet thromboxane formation and thromboxane-supported aggregation on collagen and was safe in the postoperative phase. No side effects were reported throughout the trial. The reduced toxicity with full efficacy favours a low and infrequent dosage of aspirin. PMID:6144975

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

    International Nuclear Information System (INIS)

    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. 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.

  18. Influence of hirudin and cobra venom factor on the release of 14C-serotonin and 51chromium from human platelets induced by thrombin, collagen, aggregate gammaglobulin and HLA antibody

    International Nuclear Information System (INIS)

    The present work investigates the influence of hirudin and cobra venom factor on thrombin, collagen, aggregate gammaglobulin and HLA-antibody-induced release of 14C-serotonin and 51chromium from human platelets. Besides the platelet-specific release reaction (14C-serotonin) the extent of platelet lysis was determined by measurement of the loss of 51chromium from the platelets. The results showed the thrombin, collagen and aggregate-gammaglobulin-induced platelet alteration to be a non-complement-dependent reaction of the platelets with release of 14C-serotonin. Following long-term incubation small quantities of 51chromium are also released. As this release of 51chromium cannot be inhibited using cobra venom factor and does not occur in washed platelets either, it is most probably a non-complement-dependent reaction. The HLA-antibody-induced, specific platelet alteration is both complement-dependent and complement-independent. Differentiation is possible by inhibition of the complement-dependent lysis. On the other hand thrombin is of no relevance to the collagen, aggregate gammaglobulin, and HLA-antibody-induced platelet alteration as the interactions of these substances with platelets are not inhibited by hirudin. The above results are confirmed by investigation of the 51chromium uptake capacity of washed platelets treated previously with thrombin, collagen and HLA antibody. (orig./MG)

  19. Effect of allicin (diallyl disulfide-oxide) on prostaglandin endoperoxide H2 (PGH2) and arachidonic acid (AA) metabolism and platelet aggregation

    International Nuclear Information System (INIS)

    The authors report here the effects of pure allicin (the antibacterial component of GO), synthesized from diallyl disulfide and hydrogen peroxide, on human platelet aggregation, PGH2 metabolism in microsomes of bovine lung (BL) and bovine coronary artery (BCA), homogenates of human platelet (HP), and on AA metabolism in HP. Allicin at 16 μg/ml to 160 μg/ml produced concentration-dependent inhibition of platelet aggregation to 1.6 mM AA and 2.8 μM U 46619, a stable analog of PGH2 and a TXA2 minic. BL (200 μg protein), BCA (10 μg protein), and HP (1500 μg protein) were incubated with 10 μM (14C) PGH2 +/- allicin. HP (1500 μg protein) were incubated with 20 μM (14C) AA +/- allicin. Products were separated by TLC and quantified by radiochromatographic scan. Allicin in the concentration range of 10-6M-10-3M induced no change in the formation of prostacyclin by BL and BCA or of TXA2 by BL and HP. These data suggest that the platelet antiaggregatory action of allicin is not due to inhibition of cyclooxygenase or TXA2 synthetase in the human platelet, but may be related to interactions at the TXA2 receptor or on cyclic nucleotide levels

  20. Acquired platelet function defect

    Science.gov (United States)

    ... dark black, or tarry bowel movements ; or vomiting blood or material that looks like coffee grounds Nosebleeds ... Tests that may done include: Bleeding time Platelet aggregation test Platelet count PT and PTT

  1. Selective nephroangiography in the dog causing renal platelet aggregation and irregular nephrographic phase

    International Nuclear Information System (INIS)

    Selective renal artery injections of large single doses of the ionic contrast medium metrizoate produced an irregular nephrographic phase, 'patchy contrast medium retention', in 14 of 16 dogs. The irregular nephrographic phase was associated with a transient accumulation of platelets and fibrinogen in the kidney and with microscopically demonstrable transient thrombi in afferent arterioles and glomerular capillary tufts. These effects were followed by tubular damage, which was demonstrated in 4 of 6 dogs examined 48 hours after injection. Formation of thrombi was not demonstrated in 6 dogs given small single doses, which produced a homogeneous nephrographic phase. It is suggested that contrast medium induced endothelial damage is a pathogenetic mechanism in the development of thrombi and patchy contrast medium retention. (orig.)

  2. Platelet size and age determine platelet function independently

    International Nuclear Information System (INIS)

    A study was undertaken to examine the interaction of platelet size and age in determining in vitro platelet function. Baboon megakaryocytes were labeled in vivo by the injection of 75Se-methionine. Blood was collected when the label was predominantly associated with younger platelets (day 2) and with older platelets (day 9). Size-dependent platelet subpopulations were prepared on both days by counterflow centrifugation. The reactivity of each platelet subpopulation was determined on both days by measuring thrombin-induced aggregation. Platelets were fixed after partial aggregation had occurred by the addition of EDTA/formalin. After removal of the aggregated platelets by differential centrifugation, the supernatant medium was assayed for remaining platelets and 75Se radioactivity. Comparing day 2 and day 9, no significant difference was seen in the rate of aggregation of a given subpopulation. However, aggregation was more rapid in the larger platelet fractions than in the smaller ones on both days. A greater percentage of the 75Se radioactivity appeared in the platelet aggregates on day 2 than on day 9. This effect was independent of platelet size, as it occurred to a similar extent in the unfractionated platelets and in each of the size-dependent platelet subpopulations. The data indicate that young platelets are more active than older platelets. This study demonstrates that size and age are both determinants of platelet function, but by independent mechanisms

  3. Evaluation of platelet aggregation in platelet concentrates: storage implications Efeito das catequinas (catequina e epicatequina) na agregação plaquetária

    OpenAIRE

    Teresinha J.C. Neiva; Marcos J. Machado; Monica Hoehn; Elizabeth M. Hermes; Cidônia L. Vituri; Jovino S. Ferreira; Elbio A. D'Amico

    2003-01-01

    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 s...

  4. Platelet aggregation values in patients with cardiovascular risk factors are reduced by verbascoside treatment. A randomized study.

    Science.gov (United States)

    Campo, Gianluca; Pavasini, Rita; Biscaglia, Simone; Ferri, Alessandra; Andrenacci, Elisa; Tebaldi, Matteo; Ferrari, Roberto

    2015-07-01

    Verbascoside, a phenolic compound, showed several favorable biological activities, including an antiplatelet activity. No in vivo studies tested its efficacy and safety in subjects with cardiovascular (CV) factors. The aim of this randomized, single-center, double-blind, phase II study was to assess the efficacy and tolerability of verbascoside intake for the modulation of platelet aggregation (PA) values in subjects with cardiovascular (CV) risk factors. One-hundred subjects with at least one CV risk factor (age >65 years, diabetes mellitus, hypertension, current cigarettes use, hyperlidemia, waist circumference >102 cm in male or >88 cm in female) were enrolled and randomly assigned to receive placebo or verbascoside 50mg or verbascoside 100mg. PA was measured at baseline and after 2 weeks of study drug assumption, with light transmittance aggregometry (arachidonic acid, AA, 1 μM and adenosine diphosphate, ADP, 5 μM). Two weeks of treatment with placebo or verbascoside 50mg did not modify PA values (both after AA and ADP stimuli). On the contrary, after 2 weeks of verbascoside 100mg, PA values decreased significantly (from 51 ± 13% to 39 ± 15%, p<0.01 after AA; from 60 ± 12% to 49 ± 15%, p = 0.01 after ADP). No serious adverse events were reported during the study, and no subjects discontinued the study because of adverse events. We conclude that long-term intake of verbascoside 100mg significantly reduces PA values in subjects with CV risk factors. PMID:25846253

  5. von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans.

    Science.gov (United States)

    Bauer, Alexander T; Suckau, Jan; Frank, Kathrin; Desch, Anna; Goertz, Lukas; Wagner, Andreas H; Hecker, Markus; Goerge, Tobias; Umansky, Ludmila; Beckhove, Philipp; Utikal, Jochen; Gorzelanny, Christian; Diaz-Valdes, Nancy; Umansky, Viktor; Schneider, Stefan W

    2015-05-14

    Tumor-mediated procoagulatory activity leads to venous thromboembolism and supports metastasis in cancer patients. A prerequisite for metastasis formation is the interaction of cancer cells with endothelial cells (ECs) followed by their extravasation. Although it is known that activation of ECs and the release of the procoagulatory protein von Willebrand factor (VWF) is essential for malignancy, the underlying mechanisms remain poorly understood. We hypothesized that VWF fibers in tumor vessels promote tumor-associated thromboembolism and metastasis. Using in vitro settings, mouse models, and human tumor samples, we showed that melanoma cells activate ECs followed by the luminal release of VWF fibers and platelet aggregation in tumor microvessels. Analysis of human blood samples and tumor tissue revealed that a promoted VWF release combined with a local inhibition of proteolytic activity and protein expression of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type I repeats 13) accounts for this procoagulatory milieu. Blocking endothelial cell activation by the low-molecular-weight heparin tinzaparin was accompanied by a lack of VWF networks and inhibited tumor progression in a transgenic mouse model. Our findings implicate a mechanism wherein tumor-derived vascular endothelial growth factor-A (VEGF-A) promotes tumor progression and angiogenesis. Thus, targeting EC activation envisions new therapeutic strategies attenuating tumor-related angiogenesis and coagulation. PMID:25977583

  6. Effect of onion and beet on plasma and liver lipids, platelet aggregation, and erythrocyte Na efflux in simvastatin treated hypercholesterolmic rats

    OpenAIRE

    Kim, Jung Lye; Chae, In Sook; Kang, Young Hee; Kang, Jung Sook

    2008-01-01

    This study was purposed to investigate the effect of onion or beet on plasma and liver lipids, erythrocyte Na efflux channels and platelet aggregation in simvastatin (SIM) treated hypercholesterolemic rats. Forty Sprague Dawley rats were divided into four groups and fed 0.5% cholesterol based diets containing 2 mg/kg BW simvastatin or simvastatin with 5% onion or beet powder. Plasma total cholesterol was significantly increased in SIM group compared with the control (p

  7. Low-affinity platelet factor 4 1H NMR derived aggregate equilibria indicate a physiologic preference for monomers over dimers and tetramers

    International Nuclear Information System (INIS)

    Low-affinity platelet factor 4 (LA-PF4), unlike another related, sequentially homologous platelet specific protein, platelet factor 4 (PF4), is an active mitogenic and chemotactic agent. PF4 exhibits a high binding affinity for heparin, while LA-PF4 does not. Both PF4 and LA-PF4 can exist in dimer and tetramer aggregate states. Equilibrium constants for PF4 aggregation have recently been estimated from fractional populations derived from proton nuclear magnetic resonance (NMR) integrals assigned to resonances in monomer, dimer, and tetramer states. On a 500-MHzNMR time scale, relatively slow exchange among LA-PF4 aggregate species has also allowed Tyr 15 ring proton resonances to be assigned for monomer, dimer, and tetramer states in LA-PF4. As a function of pH and ionic strength, equilibrium association constants for LA-PF4 dimer (KD) and tetramer (KT) formation have been estimated from Tyr 15 ring proton resonance integrals. Analysis of the pH dependence of KD and KT suggests that electrostatic interactions probably among Glu/Asp and Lys/Arg side chains form the predominant force in the monomer-monomer binding process, i.e., KD, while like-charge repulsion due to proximal, intersubunit Glu/Asp residues decreases KT as the pH is raised. At pH 7 and low ionic strength, the dimer state is highly favored over the tetramer state. Elevating the solvent ionic strength at pH 7 destabilizes the dimer state. Under these more physiologic conditions, i.e., pH 7 and 0.1-0.2 M NaCl, LA-PF4 monomers are highly favored over dimers and tetramers. For PF4 under similar solvent conditions, tetramers predominate. Differences in biological activities between these homologous platelet-specific proteins may be the result, at least in part, of differing aggregation properties

  8. Acacia nilotica leave extract and glyburide: comparison of fasting flood glucose, serum insulin, b-thromboglubulin levels and platelet aggregation in treptozotocin induced diabetic rats

    International Nuclear Information System (INIS)

    Objectives: To evaluate the hypoglycaemic and anti-platelet aggregation effect of aqueous methanol extract of Acacia Nilotica (AN) leaves compared with glyburide on streptozotocin induced diabetic rats. Methods: Diabetes mellitus was induced in 90 out of 120 albino rats by administering 50 mg/kg body weight (b.w) streptozotocin and was confirmed by measuring fasting blood glucose level >200 mg/dL on fourth post-induction day. The rats were equally divided into 4 groups, A (normal control), B (diabetic control), C (diabetic rats treated with AN extract) and group D (diabetic rats treated with glyburide). The rats of group C and D were given 300 mg/kg b.w AN extract and 900 mu gm/kg b.w glyburide respectively for 3 weeks. Blood glucose was measured by gluco meter, platelet aggregation by Dia-Med method and insulin and b-thrombo globulin by ELISA technique. Results: A significant increase (p<0.05) in fasting blood glucose, b-thrombo globulin and platelet aggregation and a significant decrease (p<0.05) in insulin levels was observed in streptozotocin induced diabetic rats than the normal controls. The rats treated with AN extract and glyburide showed a significant decrease (p<0.05) in fasting blood glucose and increase (p<0.05) in insulin levels than the diabetic control rats. However, the levels in both the treatment groups remained significantly different than the normal controls. A significant decrease (p<0.05) in b-thrombo globulin levels was seen in diabetic rats treated with glyburide than the diabetic control rats and diabetic rats treated with AN extract. Conclusions: AN leaves extract result into hypoglycaemic and anti-platelet aggregation activity in diabetic rats as that of glyburide. (author)

  9. The effect of two beta-adrenoceptor blockers (mepindolol and atenolol) on blood lipids and platelet aggregation in normal volunteers and essential hypertensive patients.

    OpenAIRE

    Luque Otero, M; Fernandez Pinilla, C; Escriba Polo, A; Rodriguez Vazquez, M; Martell Claros, N; A Fernandez-Cruz

    1984-01-01

    beta-adrenoceptor blocking agents are widely used as treatment of essential hypertension. We studied the action of a new non cardioselective beta-adrenoceptor blocker, mepindolol, comparing its effects on blood pressure, blood lipids and platelet aggregation with those of a cardioselective beta-adrenoceptor blocker, atenolol. Blood pressure fell significantly in the patients treated with both drugs. Triglycerides rose non-significantly only in volunteers treated with mepindolol. We did not fi...

  10. Failure of epoprostenol (prostacyclin, PGI2) to inhibit platelet aggregation and to prevent restenosis after coronary angioplasty: results of a randomised placebo controlled trial.

    OpenAIRE

    Gershlick, A H; Spriggins, D.; Davies, S W; Syndercombe Court, Y D; Timmins, J.; Timmis, A D; Rothman, M. T.; Layton, C; Balcon, R

    1994-01-01

    OBJECTIVE--To study the effect of epoprostenol (prostacyclin, PGI2) given before, during, and for 36 h after coronary angioplasty on restenosis at six months and to evaluate the transcardiac gradient of platelet aggregation before and after percutaneous transluminal coronary angioplasty (PTCA) in treated and placebo groups. DESIGN--Double blind placebo controlled randomised study. PATIENTS--135 patients with successful coronary angioplasty. METHODS--Intravenous infusion of PGI2 (4 ng/kg/ml) o...

  11. 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.

  12. Calcium(II)(3) (3,5-Diisopropylsalicylate)(6)(H(2)O)(6) Activates Nitric Oxide Synthase: An Accounting for its Action in Decreasing Platelet Aggregation.

    Science.gov (United States)

    Donham, D C; Sorenson, J R

    2000-01-01

    Purposes of these studies were first; to determine whether or not Calcium(II)(3) (3,5- diisopropylsalicylate)(6)(H(2)O)(6) [Ca(II)(3)(3,5-DIPS)(6)], a lipophilic calcium complex, could decrease activated-platelet aggregation, and second; to determine whether or not it is plausible that Ca(II)(3)(3,5-DIPS)(6) decreases activated-platelet aggregation by facilitating the synthesis of Nitric Oxide (NO) by Nitric Oxide Synthase (NOS). The influence of Ca(II)(3)(3,5-DIPS)(6) on the initial rate of activated-platelet aggregation was determined by measuring the decrease in rate of increase in transmission at 550 nm for a suspension of Thrombin-CaCl(2) activated platelets following the addition of 0, 50, 100, 250, or 500 muM Ca(II)(3)(3,5-DIPS)(6). To establish that the Ca(lI)(3)(3,5- DIPS)(6)-mediated decrease in aggregation was due to activation of NOS, the effect of L-NMMA, an inhibitor of NOS, on the inhibition of platelet aggregation by Ca(II)(3)(3,5-DIPS)(6) was determined using a suspension of activated platelets contaimng 0 or 250 muM Ca(II)(3)(3,5-DIPS)(6) without or with 1 mM L-NMMA. An in vitro Bovine Brain NOS reaction mixture, containing CaCl(2) for the activation of Phosphodiesterase-3' ,5'-Cyclic Nucleotide Activator required for the activation of NOS, was used to determine whether or not Ca(II)(3)(3,5-DIPS)(6) could be used as a substitute for the addition of Ca. The decrease in absorbance at 340 nm, lambda maximum for NADPH, was measured to determine NOS activity following the addition of NOS to the complete reaction mixture containing either CaCl(2), Ca(II)(3)(3,5-DIPS)(6), or neither Ca compound. Increasing the concentration of Ca(II)(3)(3,5-DIPS)(6) caused a concentration related decrease in activated platelet aggregation. The addition of L-NMMA to activated platelets, in the absence of Ca(II)(3)(3,5-DIPS)(6), caused a 129% increase in initial rate of platelet aggregation. The initial rate of platelet aggregation decreased 74% with the addition of 250 mu

  13. Balancing Potency of Platelet Inhibition with Bleeding Risk in the Early Treatment of Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Slattery, David E

    2009-08-01

    Full Text Available Objective: To review available evidence and examine issues surrounding the use of advanced antiplatelet therapy in an effort to provide a practical guide for emergency physicians caring for patients with acute coronary syndromes (ACS.Data Sources: American College of Cardiology/American Heart Association (ACC/AHA 2007 guidelines for the management of patients with unstable angina (UA and non-ST-segment elevation myocardial infarction (NSTEMI, AHA/ACC 2007 focused update for the management of patients with STEMI, selected clinical articles identified through the PubMed database (1965-February 2008, and manual searches for relevant articles identified from those retrieved.Study Selection: English-language controlled studies and randomized clinical trials that assessed the efficacy and safety of antiplatelet therapy in treating patients with all ACS manifestations.Data Extraction and Synthesis: Clinical data, including treatment regimens and patient demographics and outcomes, were extracted and critically analyzed from the selected studies and clinical trials. Pertinent data from relevant patient registries were also evaluated to assess current clinical practice.Conclusions: As platelet activation and aggregation are central to ACS pathology, antiplatelet agents are critical to early treatment. A widely accepted first-line treatment is aspirin, which acts to decrease platelet activation via inhibition of thromboxane A2 synthesis. Thienopyridines, which inhibit ADP-induced platelet activation, and glycoprotein (GP receptor antagonists, which bind to platelet GP IIb/IIIa receptors and hinder their role in platelet aggregation and thrombus formation, provide complementary mechanisms of platelet inhibition and are often employed in combination with aspirin. While the higher levels of platelet inhibition that accompany combination therapy improve protection against ischemic and peri-procedural events, the risk of bleeding is also increased. Thus, the

  14. 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.

  15. Isolation of Bioactive Compounds That Relate to the Anti-Platelet Activity of Cymbopogon ambiguus

    Directory of Open Access Journals (Sweden)

    I. Darren Grice

    2011-01-01

    Full Text Available Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in Australia for the treatment of headache, chest infections and muscle cramps. The aim of the present study was to screen and identify bioactive compounds from C. ambiguus that could explain this plant’s anti-headache activity. A dichloromethane extract of C. ambiguus was identified as having activity in adenosine-diphosphate-induced human platelet aggregation and serotonin-release inhibition bioassays. Subsequent fractionation of this extract led to the isolation of four phenylpropenoids, eugenol, elemicin, eugenol methylether and trans-isoelemicin. While both eugenol and elemicin exhibited dose-dependent inhibition of ADP-induced human platelet serotonin release, only eugenol displayed potent inhibitory activity with an IC50 value of 46.6 μM, in comparison to aspirin, with an IC50 value of 46.1 μM. These findings provide evidence to support the therapeutic efficacy of C. ambiguus in the non-conventional treatment of headache and inflammatory conditions.

  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. 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.

  18. 毛葡萄叶水提物抑制血小板聚集的初步研究%Preliminary Study on Effects of Extracts of Vitis Quinquangularis Rehd Leaves on Inhibition of Platelet Aggregation

    Institute of Scientific and Technical Information of China (English)

    任丽洁; 杨飞; 张灿灿; 米辰; 杨林; 朱力; 吴开云

    2011-01-01

    Objective To study the effect of extract of Vitis quinquangularis Rehd leaves ( Gx) on platelet aggregation. Methods Isolated healthy human platelets were incubated with Gx at different concentration for 10 minutes at 37 t ,and were stimulated with collagen and thrombin, then platelet aggregation was performed. After intraperitoneal injection of Gx, isolated mouse platelets were stimulated with ADP to examine the change of platelet aggregation. Results Human platelet aggregation incuced by 2 |xg/ml collagen was dose-dependently inhibited by Gx(P <0. 05) ; but only 0. 01 g/ml Gx was able to inhibit human platelet aggregation induced by 0.1 U/ml thrombin, in a Gx dose-undependent way. And Gx was able to inhibit platelet aggregation induced by ADP in the intraperitoneally injected mice. Conclusion Gx can obviously inhibit platelet aggregation, and it can provide a experimental basis for development of antithrombotic drugs.%目的 探讨毛葡萄叶水提物(Gx)对血小板聚集的影响.方法 分离健康人的血小板,与不同生药浓度的Gx于37℃孵育10 min后,检测胶原(collagen)和凝血酶(thrombin)诱导的人血小板聚集的变化.小鼠腹腔注射Gx后,分离小鼠血小板,检测二磷酸腺苷(ADP)诱导的血小板聚集的变化.结果 Gx对2μg/ml collagen诱导的血小板聚集有显著抑制作用(P<0.05),且呈现Gx的剂量依赖性(P<0.05);只有0.01mg/ml的Gx对0.1 U/mlthrombin诱导的血小板聚集有抑制作用,且不呈现Gx的剂量依赖性.同时,Gx可抑制ADP诱导的腹腔注射Gx的小鼠血小板聚集,且呈现ADP剂量依赖性.结论 Gx具有明显抗血小板聚集作用,为开发抗血栓药物提供了实验依据.

  19. Clinical study on platelet inhibition functions of Puerarin in patients with aspirin resistance%葛根素对阿司匹林抵抗患者血小板功能影响的临床研究

    Institute of Scientific and Technical Information of China (English)

    王晶; 杨俊杰; 田峰; 董静; 周迎; 杨晓波; 陈韵岱

    2012-01-01

    目的 研究葛根素对阿司匹林抵抗患者血小板功能的影响.方法 采用单中心双盲、对照临床试验共入选180例冠心病住院患者,以花生四烯酸诱导的血小板聚集率>50%和二磷酸腺苷诱导的血小板聚集率≥70%作为血小板高反应性的标准,将患者随机分成葛根素+氯吡格雷组(葛根素组)和阿司匹林+氯吡格雷组(阿司匹林组),比较第3天和第7天后患者的血小板功能及相关生化指标.结果 与阿司匹林组比较,葛根素组在第3天和第7天均可明显改善AA途径诱导的血小板抑制率(P 50% and ADP-induced aggregation ≥ 70% with TEG protocol). All patients were divided into two groups including Puerarin+Clopidogrel group (Puerarin group) and Aspirin+Clopidogrel group (Aspirin group). The platelet aggregation functions, as well as relative TXA2 metabolic product biomarker were measured in indicated time. Results On 3rd and 7th day, AA-induced platelet inhibition percentage can be significantly improved in Puerarin group than that in Aspirin group (P < 0.01). Puerarin group could also obtain better ADP-induced platelet inhibition percentage than Aspirin group (P < 0.05) on 3rd day. As to TXA2 metabolite, urinary 11-DH-TXB2 could be significantly reduced in PC group compared with Aspirin group both on 3rd and 7th day (P < 0.05). Conclusion Puerarin can effectively improve high platelet response in patients with Aspirin resistance, and thus help reach an ideal level for platelet inhibition.

  20. Platelet viability (aggregation, migration, recovery) after radiolabelling from hypercholesterolemcis using various tracers (oxine, oxine-sulphate, tropolone, MPO)

    International Nuclear Information System (INIS)

    Earlier results indicated a diminished labelling efficiency and recovery negatively linked to actual cholesterol and lipoprotein values in hyperlipoproteinemics. This study was designed to examine whether other alternative tracers exhibit similar results and to study the influence on platelet viability in the presence or absence of PGI2. We demonstrate that no substantial difference occurs between the four tracers concerning labelling efficiency and recovery in normo and hypercholesterolemics. Cholesterol severely affects the labelling parameters for all the tracers to a comparable extent. The absolute platelet function varies considerably, however, the percent changes in normo and hypercholesterolemics seen before and after the labelling procedure do not differ significantly. PGI2 improves recovery in general, however, without affecting labelling efficiency or in vitro viability testing. As prolonged incubation further increases labelling efficiency, the presence and extent of hyperlipoproteinemia should be known in order to avoid poor labelling and viability and subsequently poor clinical results. (orig.)

  1. Anti-CD31 delays platelet adhesion/aggregation at sites of endothelial injury in mouse cerebral arterioles.

    OpenAIRE

    Rosenblum, W. I.; Murata, S.; Nelson, G. H.; Werner, P K; Ranken, R.; Harmon, R C

    1994-01-01

    The arterioles on the surface of the mouse brain (pial arterioles) were observed by in vivo microscopy. A focus of minor endothelial damage was produced in a single pial arteriole in each mouse by briefly exposing the site to a helium neon laser after an intravenous injection of Evans blue. Mice were injected 10 minutes before injury with a monoclonal antibody (MAb) to mouse CD31, also known as platelet endothelial cell adhesion molecule. This treatment doubled (P < .01) the time required for...

  2. Subpopulations in purified platelets adhering on glass.

    Science.gov (United States)

    Donati, Alessia; Gupta, Swati; Reviakine, Ilya

    2016-01-01

    Understanding how platelet activation is regulated is important in the context of cardiovascular disorders and their management with antiplatelet therapy. Recent evidence points to different platelet subpopulations performing different functions. In particular, procoagulant and aggregating subpopulations have been reported in the literature in platelets treated with the GPVI agonists. How the formation of platelet subpopulations upon activation is regulated remains unclear. Here, it is shown that procoagulant and aggregating platelet subpopulations arise spontaneously upon adhesion of purified platelets on clean glass surfaces. Calcium ionophore treatment of the adhering platelets resulted in one platelet population expressing both the procoagulant and the adherent population markers phosphatidylserine and the activated form of GPIIb/IIIa, while all of the platelets expressed CD62P independently of the ionophore treatment. Therefore, all platelets have the capacity to express all three activation markers. It is concluded that platelet subpopulations observed in various studies reflect the dynamics of the platelet activation process. PMID:27338300

  3. Medicinal flowers. XV. The structures of noroleanane- and oleanane-type triterpene oligoglycosides with gastroprotective and platelet aggregation activities from flower buds of Camellia japonica.

    Science.gov (United States)

    Yoshikawa, Masayuki; Morikawa, Toshio; Asao, Yasunobu; Fujiwara, Emi; Nakamura, Seikou; Matsuda, Hisashi

    2007-04-01

    The methanolic extract from the flowers buds of Camellia japonica L. (Theaceae) were found to exhibit potent inhibitory activities on ethanol- or indomethacin-induced gastric mucosal lesions in rats. Through bioassay-guided separation, 28-noroleanane-type triterpene oligoglycosides, camelliosides A, B, and C, and an oleanane-type triterpene oligoglycoside, camellioside D, were isolated from the methanolic extract together with five known compounds. The absolute stereostructures of camelliosides were determined on the basis of chemical and physicochemical evidence, which included the structure revision of the nortriterpene aglycons (camellenodiol and camelledionol). The principal oligoglycosides, camelliosides A and B, showed platelet aggregation activity in addition to the gastroprotective effects on ethanol- or indomethacin-induced gastric mucosal lesions in rats. PMID:17409556

  4. Purification and characterization of a platelet aggregation inhibitor acidic phospholipase A2 from Indian saw-scaled viper (Echis carinatus) venom.

    Science.gov (United States)

    Kemparaju, K; Krishnakanth, T P; Veerabasappa Gowda, T

    1999-12-01

    An acidic phospholipase A2 (EC-I-PLA2) has been purified from the Indian saw-scaled viper (Echis carinatus) venom through a combination of column chromatography and electrophoresis. EC-I-PLA2 has a molecular weight of 16000 by SDS-PAGE. It was focussed between pH 4.2 and 4.8 by isoelectro focussing. EC-I-PLA2 was non-lethal to mice and devoid of neurotoxicity, myotoxicity, anticoagulant activity and cytotoxicity. It induced mild oedema in the foot pads of mice. The purified PLA2 inhibited ADP, collagen and epinephrine induced human platelet aggregation and the inhibition was both dose and time dependent. PMID:10519645

  5. Hepatic transformation of prostaglandin D2 to a new prostanoid, 9 alpha,11 beta-prostaglandin F2, that inhibits platelet aggregation and constricts blood vessels

    International Nuclear Information System (INIS)

    The metabolic transformation of tritium-labeled prostaglandin D2 ([3H]PGD2) was investigated in the isolated Tyrode's-perfused rabbit liver. One major product was isolated and identified in the perfusate as a new prostanoid. The structure of this metabolite was further confirmed by gas chromatography-mass spectrometry and chemical methods to be 9 alpha,11 beta,15-L-trihydroxyprosta-5-cis, 13-trans-dienoic acid, namely (9 alpha,11 beta-PGF2). This new prostanoid was found to be an inhibitor of platelet aggregation and to cause constriction of canine coronary artery strips. These results suggested that on passage through the hepatic circulation exogenous PGD2 is converted to 9 alpha,11 beta-PGF2, the latter having a biological profile which differs from that of PGD2 and PGF2 alpha

  6. 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

  7. Crystallization and preliminary X-ray diffraction studies of BmooPLA2-I, a platelet-aggregation inhibitor and hypotensive phospholipase A2 from Bothrops moojeni venom

    International Nuclear Information System (INIS)

    BmooPLA2-I, an acidic, catalytic and nontoxic phospholipase A2 from B. moojeni venom that is able to inhibit platelet aggregation and induce a hypotensive effect, has been crystallized. An X-ray diffraction data set was collected to 1.6 Å resolution and a molecular-replacement solution was obtained. Phospholipases A2 (PLA2s) are enzymes that cause the liberation of fatty acids and lysophospholipids by the hydrolysis of membrane phospholipids. In addition to their catalytic action, a wide variety of pharmacological activities have been described for snake-venom PLA2s. BmooPLA2-I is an acidic, nontoxic and catalytic PLA2 isolated from Bothrops moojeni snake venom which exhibits an inhibitory effect on platelet aggregation, an immediate decrease in blood pressure, inducing oedema at a low concentration, and an effective bactericidal effect. BmooPLA2-I has been crystallized and X-ray diffraction data have been collected to 1.6 Å resolution using a synchrotron-radiation source. The crystals belonged to space group C2221, with unit-cell parameters a = 39.7, b = 53.2, c = 89.2 Å. The molecular-replacement solution of BmooPLA2-I indicated a monomeric conformation, which is in agreement with nondenaturing electrophoresis and dynamic light-scattering experiments. A comparative study of this enzyme with the acidic PLA2 from B. jararacussu (BthA-I) and other toxic and nontoxic PLA2s may provide important insights into the functional aspects of this class of proteins

  8. Preliminary studies of a platelet function disorder in Simmental cattle.

    OpenAIRE

    Searcy, G. P.; Sheridan, D; Dobson, K A

    1990-01-01

    A bleeding disorder due to abnormal platelet function occurs in Simmental cattle. Whole blood from these animals underwent good clot retraction. Platelet aggregation in response to adenosine diphosphate (ADP) and collagen in a whole blood aggregation system was markedly impaired. Normal bovine platelets in a whole blood aggregation system showed very little aggregation in response to epinephrine and arachidonic acid. Aggregation in platelet-rich plasma was negligible in response to ADP, colla...

  9. Genetic Determinants of On-Aspirin Platelet Reactivity: Focus on the Influence of PEAR1

    OpenAIRE

    Würtz, Morten; Nissen, Peter H; Grove, Erik Lerkevang; Kristensen, Steen Dalby; Hvas, Anne-Mette

    2014-01-01

    Background Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals. Aim To identify platelet-related single nucleotide polymorphisms (SNPs) influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation...

  10. Effects of fused hirudin on activity of thrombin and function of platelets

    Institute of Scientific and Technical Information of China (English)

    SHEN Li; CHEN Shao-ping; CAI Zai-long; YANG Sheng-sheng; QIN Yong-wen

    2005-01-01

    Objective: To investigate whether fused hirudin peptide has both antithrombin and antiplatelet functions. Methods: The core region of fused hirudin was the C-terminal tail of hirudin(hirudin53-64),which could bind to the anion binding exosite (ABE) of thrombin.Arg-Pro-Pro-Gly-Phe(RPPGF) amino acid sequence,a metabolite of bradykinin,was added to the N-terminus of hirudin53-64.It bound to the active site of thrombin.Additionally,Arg-Gly-Asp(RGD)amino acid sequence,an inibitor of glycoprotein Ⅱb/Ⅲa( GP Ⅱb/Ⅲa) receptor,was linked to C-terminus of hirudin53-64.This 26-animo acid-fused hirudin peptide was artificially synthesized,purified and analysed. Results: Fused hirudin peptide significantly lengthened the activated partial thromboplastin time(APTT),thrombin time(TT)and prothrombin time(PT) and inhibited the amidolytic activity of thrombin.The ADP-induced platelet aggregation was markedly inhibited by fused hirudin peptide. Conclusion: Fused hirudin peptide has activity of antithrombin as well as antiplatelet.Therefore bifunctional anticoagulation peptide has capacity to target various components of haemostatic process and may become more powerful antithrombosis agent.

  11. [THE REFERENCE VALUES OF AGGREGATION OF PLATELETS IN ADULT POPULATION OF THE ASTRAKHAN OBLAST USING AGGREGOMETER MULTIPLATE].

    Science.gov (United States)

    Petrova, O V; Shashin, S A; Tarasov, D G; Jukova, E R; Panova, E V; Gracheva, N P

    2016-01-01

    The modern international standards recommend each laboratory to develop or to confirm available in literature the reference intervalsfor every laboratory indicator In the Astrakhanskaia oblast, sampling of128 healthy males andfemales were examinedfor aggregation function of thrombocytes using impedance technique and applying aggregometer Multiplate ("Verum Diagnostica", Germany). The study used as inductors peptide activating receptor of thrombin; arachidonic and adenosine diphosphoric acids. The reference range of aggregation of thrombocytes with peptide activating receptor of thrombin, at aggregometer Multiplate, in healthy population of theAstrakhanskaia oblast made up to 815.2-1498.4 AU/min, with arachidonic acid--660-1341 AU/min. with adenosine diphosphoric acid--598-1120 AU/min. PMID:27183729

  12. Niacin and biosynthesis of PGD₂ by platelet COX-1 in mice and humans

    DEFF Research Database (Denmark)

    Song, Wen-Liang; Stubbe, Jane; Ricciotti, Emanuela; Alamuddin, Naji; Ibrahim, Salam; Crichton, Irene; Prempeh, Maxwell; Lawson, John A; Wilensky, Robert L; Rasmussen, Lars Melholt; Puré, Ellen; FitzGerald, Garret A

    2012-01-01

    thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD₂ was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD₂, like PGI₂, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular...... during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis....... Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1-derived PGD₂ biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased...

  13. 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.

  14. Approaches to synthetic platelet analogs.

    Science.gov (United States)

    Modery-Pawlowski, Christa L; Tian, Lewis L; Pan, Victor; McCrae, Keith R; Mitragotri, Samir; Sen Gupta, Anirban

    2013-01-01

    Platelet transfusion is routinely used for treating bleeding complications in patients with hematologic or oncologic clotting disorders, chemo/radiotherapy-induced myelosuppression, trauma and surgery. Currently, these transfusions mostly use allogeneic platelet concentrates, while products like lyophilized platelets, cold-stored platelets and infusible platelet membranes are under investigation. These natural platelet-based products pose considerable risks of contamination, resulting in short shelf-life (3-5 days). Recent advances in pathogen reduction technologies have increased shelf-life to ~7 days. Furthermore, natural platelets are short in supply and also cause several biological side effects. Hence, there is significant clinical interest in platelet-mimetic synthetic analogs that can allow long storage-life and minimum side effects. Accordingly, several designs have been studied which decorate synthetic particles with motifs that promote platelet-mimetic adhesion or aggregation. Recent refinement in this design involves combining the adhesion and aggregation functionalities on a single particle platform. Further refinement is being focused on constructing particles that also mimic natural platelet's shape, size and elasticity, to influence margination and wall-interaction. The optimum design of a synthetic platelet analog would require efficient integration of platelet's physico-mechanical properties and biological functionalities. We present a comprehensive review of these approaches and provide our opinion regarding the future directions of this research. PMID:23092864

  15. 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 < 0.001) and 40 mg/kg (P < 0.01). Similar effects were observed in pial venules with 10 mg/kg (P < 0.05) and 40 mg/kg (P < 0.05) 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. PMID:25662827

  16. Platelet Disorders

    Science.gov (United States)

    ... higher risk of blood clots. With other platelet disorders, the platelets do not work as they should. ... This can cause excessive bleeding. Treatment of platelet disorders depends on the cause. NIH: National Heart, Lung, ...

  17. Platelet proteomics in cardiovascular diseases

    OpenAIRE

    Paula Vélez; Ángel García

    2015-01-01

    In recent years, platelet proteomics has been applied successfully to the study of cardiovascular diseases (CVDs). It is very well known that platelets play a pivotal role in the pathophysiological mechanisms underlying many CVDs, especially acute coronary syndromes (ACSs), since they are implied in thrombus formation after atheroma plaque rupture. This is the reason why molecules involved in platelet activation and aggregation are primary targets for treatment of ACSs. Many efforts are aimed...

  18. Platelet proteomics in cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Paula Vélez

    2015-06-01

    Full Text Available In recent years, platelet proteomics has been applied successfully to the study of cardiovascular diseases (CVDs. It is very well known that platelets play a pivotal role in the pathophysiological mechanisms underlying many CVDs, especially acute coronary syndromes (ACSs, since they are implied in thrombus formation after atheroma plaque rupture. This is the reason why molecules involved in platelet activation and aggregation are primary targets for treatment of ACSs. Many efforts are aimed at finding drugs that inhibit platelet activation; however it is difficult to separate the therapeutic benefits from harmful effects because pathological and physiological functions of platelets are due to the same mechanisms. Given that platelets lack a nucleus, proteomics is regarded as an ideal method to approach their biochemistry. Current platelet proteomic studies are focusing on the identification of platelet molecular and functional changes in normal and pathological states, enriching the comprehension of platelet biological function, and screening for new biomarkers and antiplatelet agents. In the present article, we introduce the reader to platelet biology and function, and revise recent advances in platelet proteomics applied to the study of CVDs, including a special emphasis on sample preparation requirements for proteome analysis of platelet clinical samples.

  19. Radiolabeled platelets

    International Nuclear Information System (INIS)

    Initial interest in developing techniques to radiolabel platelets was spurred by the lack of an accurate method for measuring platelet life span in both normals and in thrombocytopenic patients. Early investigators could obtain only rough estimates of platelet life spans by monitoring the platelet counts of thrombocytopenic patients undergoing platelet transfusions. Labels were also sought that would allow imaging of platelets in vivo in order to better understand the pathophysiology of atherosclerosis, thrombophlebitis, and clotting disorders, and to improve the clinical diagnosis of these diseases. Two types of platelet labels were investigated: cohort (pulse) labels and random labels. Cohort labels are taken up by megakaryocytes in the bone marrow and incorporated in the DNA and other components of the forming platelet. In theory, only freshly released platelets of a uniform age are labeled. Random labels, on the other hand, tag platelets in the peripheral blood, labeling platelets of all ages

  20. The Kinetics of Circulating Monocyte Subsets and Monocyte-Platelet Aggregates in the Acute Phase of ST-Elevation Myocardial Infarction

    Science.gov (United States)

    Zhou, Xin; Liu, Xin-Lin; Ji, Wen-Jie; Liu, Jun-Xiang; Guo, Zhao-Zeng; Ren, Dong; Ma, Yong-Qiang; Zeng, Shan; Xu, Zhong-Wei; Li, Hong-Xia; Wang, Peizhong Peter; Zhang, Zhuoli; Li, Yu-Ming; Benefield, Brandon C.; Zawada, Adam M.; Thorp, Edward B.; Lee, Daniel C.; Heine, Gunnar H.

    2016-01-01

    Abstract In experimental myocardial infarction (MI), a rise in cell counts of circulating monocyte subsets contributes to impaired myocardial healing and to atherosclerotic plaque destabilization. In humans, the prognostic role of monocyte subsets in patients suffering ST-elevation MI (STEMI) is still unclear. In the present study, we aimed to determine the kinetics of the 3 monocyte subsets (classical CD14++CD16–, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes), as well as the subset-specific monocyte–platelet aggregates (MPA), in acute STEMI followed by primary percutaneous coronary intervention (PCI), and their relationships with cardiovascular outcomes during a 2-year follow-up. Monocyte subsets and MPA were measured in 100 STEMI patients receiving primary PCI on days 1, 2, 3, 5, and 7 of symptom onset, which were compared with 60 stable coronary heart disease patients and 35 healthy volunteers. From day 1 to day 7, significant increases in the counts of CD14++CD16+ monocytes and CD14++CD16+ MPA were observed, with peak levels on day 2. During a median follow-up of 2.0 years, 28 first cardiovascular events (defined as cardiovascular death, nonfatal ischemic stroke, recurrent MI, need for emergency or repeat revascularization, and rehospitalization for heart failure) were recorded. After adjustment for confounders, CD14++CD16+ monocytosis (day 1 [HR: 3.428; 95% CI: 1.597–7.358; P = 0.002], day 2 [HR: 4.835; 95% CI: 1.106–21.13; P = 0.04], day 3 [HR: 2.734; 95% CI: 1.138–6.564; P = 0.02], and day 7 [HR: 2.647; 95% CI: 1.196–5.861; P = 0.02]), as well as increased levels of CD14++CD16+ MPA measured on all time points (days 1, 2, 3, 5, and 7), had predictive values for adverse cardiovascular events. In conclusion, our data show the expansion of the CD14++CD16+ monocyte subset during acute phase of STEMI has predictive values for 2-year adverse cardiovascular outcomes in patients treated with primary PCI. Future studies

  1. Ethyl Acetate Extract from Tissue-Cultured Mountain Ginseng Adventitious Roots Inhibits In Vitro Platelet Aggregation in Whole Human Blood and Augments Peripheral Blood Flow in Mice

    OpenAIRE

    Lee, In Sun; Kim, Seul-Ki; Jeon, Min Hwa; Jeon, Won Kyung

    2011-01-01

    We previously reported that in vitro anti-platelet activity of tissue-cultured mountain ginseng (TCMG) ethanol extracts show improved efficacy when compared with commercial ginseng products such as Korean red ginseng and Panax ginseng. However, information on the anti-platelet activity of the ethyl acetate fraction from TCMG adventitious roots is limited. Therefore, in this study, we further investigated the effects of an ethyl acetate extract of TCMG (EA-TCMG) adventitious roots on in vitro ...

  2. Nucleolin down-regulation is involved in ADP-induced cell cycle arrest in S phase and cell apoptosis in vascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Wenmeng Wang

    Full Text Available High concentration of extracellular ADP has been reported to induce cell apoptosis, but the molecular mechanisms remain not fully elucidated. In this study, we found by serendipity that ADP treatment of human umbilical vein endothelial cells (HUVEC and human aortic endothelial cells (HAEC down-regulated the protein level of nucleolin in a dose- and time-dependent manner. ADP treatment did not decrease the transcript level of nucloelin, suggesting that ADP might induce nucleolin protein degradation. HUVEC and HAEC expressed ADP receptor P2Y13 receptor, but did not express P2Y1 or P2Y12 receptors. However, P2Y1, 12, 13 receptor antagonists MRS2179, PSB0739, MRS2211 did not inhibit ADP-induced down-regulation of nucleolin. Moreover, MRS2211 itself down-regulated nucleolin protein level. In addition, 2-MeSADP, an agonist for P2Y1, 12 and 13 receptors, did not down-regulate nucleolin protein. These results suggested that ADP-induced nucleolin down-regulation was not due to the activation of P2Y1, 12, or 13 receptors. We also found that ADP treatment induced cell cycle arrest in S phase, cell apoptosis and cell proliferation inhibition via nucleolin down-regulation. The over-expression of nucleolin by gene transfer partly reversed ADP-induced cell cycle arrest, cell apoptosis and cell proliferation inhibition. Furthermore, ADP sensitized HUVEC to cisplatin-induced cell death by the down-regulation of Bcl-2 expression. Taken together, we found, for the first time to our knowledge, a novel mechanism by which ADP regulates cell proliferation by induction of cell cycle arrest and cell apoptosis via targeting nucelolin.

  3. Effect of Indobufen on Platelet Aggregation and Coagulation in Type 2 Diabetic Patients%吲哚布芬对2型糖尿病患者血小板聚集及凝血机制的影响

    Institute of Scientific and Technical Information of China (English)

    林昱; 方懿珊; 黄家庆

    2011-01-01

    [目的]观察吲哚布芬对2型糖尿病患者血小板聚集功能及凝血机制的影响.[方法]分别以比浊法和凝固法检测应用吲哚布芬治疗前后2型糖尿病患者的血小板最大聚集率(MAR)和凝血全套各指标的变化.[结果]经吲哚布芬治疗后,61例2型糖尿病患者活化部分凝血活酶时间(APTT)、纤维蛋白原凝固时间(FIBT)明显延长(P0.05).[结论]吲哚布芬可抑制2型糖尿病患者的血小板聚集及改善其血流动力学,而对PT、TT、INR等无明显影响,是2型糖尿病患者抗血小板治疗的一种安全有效药物.%[Objective] To observe the effect of indobufen on platelet aggregation and coagulation of type 2 diabetic patients. [Methods]The changes of maximal platelet aggregation(MAR) and indices of blood coagula tion were observed before and after indobufen was used for the treatment of type 2 diabetic patients by using turbidimetry and freezing method. [Results] After the treatment with indobufen, activated partial thrombo plastin time(APTT) and fibrinogen clotting time(FIBT) of 61 patients with type 2 diabetes mellitus were pro longed obviously( P 0. 05). [Conclusion[ Indobufen can inhibit platelet aggregation and improve the hemodynamics in type 2 dia betic patients, and has no effect on PT, TT and INR. Therefore, it is safe and effective in anti platelet aggre gation treatment of type 2 diabetic patients.

  4. In vivo anti-platelet aggregation effects of andrographis paniculta lactone%穿心莲内酯在动物体内抗血小板凝聚的实验研究

    Institute of Scientific and Technical Information of China (English)

    冯玉丽; 占葆娥; 张书楠; 李秀玉; 侯智辉; 袁敏

    2013-01-01

    Objective To analyze the anti-platelet aggregation effects of andrographis paniculta lactone in animal body and confirm the exact role to provide reference for clinical medication.Methods 30 healthy rats fed in laboratory were selected and randomly divided into three groups,including control group fed quantitative physiological saline,observation group 1 fed andrographis paniculta lactone for 50 mg/kg and observation group 2 fed andrographis paniculta lactone for 100 mg/kg.Using platelet aggregation and thrombosis instrument to detect the largest platelet aggregation rate and thrombosis time,and comparison and statistical analysis were performed.Results The largest platelet aggregation rate and thrombosis time in observation group 1 and 2 were statistically different with control group(P<0.05) and also with statistical difference between the two observation groups(P<0.05).Conclusion Andrographis paniculta lactone could significantly inhibit the platelet aggregation and thrombosis in rats,and this effects could be enhanced with the increasing of the drug dosage.%目的 对穿心莲内酯在动物体内的抗血小板凝聚作用进行分析,证实其确切的作用,为临床用药提供参考.方法 选取实验室养殖的健康大鼠30只为研究对象,将其随机分为3组:(1)对照组,服用定量的生理盐水;(2)观察1组,按50 mg/kg的剂量服用穿心莲内酯;(3)观察2组,按100 mg/kg的剂量服用穿心莲内酯.使用血小板凝聚仪及血栓形成仪对各组研究对象的血小板最大凝聚率和血栓形成时间进行测定,并进行比较及统计学分析.结果 观察1组、观察2组研究对象的血小板最大凝聚率及血栓形成时间均较对照组有明显优势,经统计学分析,差异具有统计学意义(P<0.05);对观察1组和观察2组的血小板最大凝聚率及血栓形成时间进行组间比较,观察2组有明显优势,经统计学分析,差异具有统计学意义(P<0.05).结论 穿心莲内酯对大鼠体

  5. 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.

  6. Deposition of In-111-labeled platelets after percutaneous transluminal angioplasty

    International Nuclear Information System (INIS)

    Platelet aggregation is presumed to occur at angioplasty sites after intimal disruption. This deposition may lead to acute thromboembolic events and is probably an initial event in recurring arteriosclerotic plaque formation. Thus far the author have studied this process in ten patients undergoing percutaneous transluminal angioplasty (PTA) by labeling the patient's platelets with In-111 on the day prior to PTA. The patient is imaged before the angioplasty procedure and 4 and 24 hours after the procedure. Platelet aggregation at the angioplasty site can be visualized and platelet volume quantified in all patients. The technique is being used in the evaluation of platelet aggregation after PTA. The author attempt to determine the frequency and volume of aggregation, correlate these findings with physical findings, assess the effect of platelet-inhibiting drugs, and assess the anatomic site of angioplasty in terms of predilection for platelet aggregation

  7. Platelet kinetics

    International Nuclear Information System (INIS)

    Recently, the in vivo processes of platelet function and the reaction and interaction of platelets with components of the blood vessel wall and artificial surfaces have received increasing attention. In this article the focus is placed on two aspects of platelet function and kinetics as revealed by 111In-labelled platelets. First the interaction of platelets with foreign prosthetic surfaces is discussed and some interesting facets of platelet functions that have come to light, are pointed out. Secondly, experiences with the development and refinement of an improved technique, namely the dual-isotope subtraction method, which increases the sensitivity of platelet imaging and allows the detection of relatively small areas of platelet deposition with accuracy, are described

  8. 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...

  9. Myeloperoxidase induces the priming of platelets.

    Science.gov (United States)

    Kolarova, H; Klinke, A; Kremserova, S; Adam, M; Pekarova, M; Baldus, S; Eiserich, J P; Kubala, L

    2013-08-01

    The release of myeloperoxidase (MPO) from polymorphonuclear neutrophils is a hallmark of vascular inflammation and contributes to the pathogenesis of vascular inflammatory processes. However, the effects of MPO on platelets as a contributory mechanism in vascular inflammatory diseases remain unknown. Thus, MPO interaction with platelets and its effects on platelet function were examined. First, dose-dependent binding of MPO (between 1.7 and 13.8nM) to both human and mouse platelets was observed. This was in direct contrast to the absence of MPO in megakaryocytes. MPO was localized both on the surface of and inside platelets. Cytoskeleton inhibition did not prevent MPO localization inside the three-dimensional platelet structure. MPO peroxidase activity was preserved upon the MPO binding to platelets. MPO sequestered in platelets catabolized NO, documented by the decreased production of NO (on average, an approximately 2-fold decrease). MPO treatment did not affect the viability of platelets during short incubations; however, it decreased platelet viability after long-term storage for 7 days (an approximately 2-fold decrease). The activation of platelets by MPO was documented by an MPO-mediated increase in the expression of surface platelet receptors P-selectin and PECAM-1 (of about 5 to 20%) and the increased formation of reactive oxygen species (of about 15 to 200%). However, the activation was only partial, as MPO did not induce the aggregation of platelets nor potentiate platelet response to classical activators. Nor did MPO induce a significant release of the content of granules. The activation of platelets by MPO was connected with increased MPO-treated platelet interaction with polymorphonuclear leukocytes (an approximately 1.2-fold increase) in vitro. In conclusion, it can be suggested that MPO can interact with and activate platelets, which can induce priming of platelets, rather than the classical robust activation of platelets. This can contribute to the

  10. Platelet dysfunction and inhibition of multiple electrode platelet aggregometry caused by penicillin

    Directory of Open Access Journals (Sweden)

    von Beckerath Nicolas

    2010-07-01

    Full Text Available Abstract Beta-lactam antibiotics, e.g. penicillin, may inhibit platelet function and lead to reduced response in light transmission aggregometry and adhesion. However, influence on platelet function tests more commonly used in clinical practice, such as multiple electrode platelet aggregometry (MEA, have not been described so far. We report a case of a patient with local streptococcus infection. Treatment with penicillin resulted in mild bleeding tendency after 3 days. While coagulation parameters were normal, assessment of platelet function by MEA revealed strong platelet inhibition of both ADP and arachidonic acid induced platelet aggregation comparable to normal responders to antiplatelet therapy. Change of antibiotic regime resulted in recovery of platelet function. Thus, penicillin therapy may impact on platelet function and consecutively commonly used platelet function assays, e.g. MEA.

  11. Rupture Forces among Human Blood Platelets at different Degrees of Activation.

    Science.gov (United States)

    Nguyen, Thi-Huong; Palankar, Raghavendra; Bui, Van-Chien; Medvedev, Nikolay; Greinacher, Andreas; Delcea, Mihaela

    2016-01-01

    Little is known about mechanics underlying the interaction among platelets during activation and aggregation. Although the strength of a blood thrombus has likely major biological importance, no previous study has measured directly the adhesion forces of single platelet-platelet interaction at different activation states. Here, we filled this void first, by minimizing surface mediated platelet-activation and second, by generating a strong adhesion force between a single platelet and an AFM cantilever, preventing early platelet detachment. We applied our setup to measure rupture forces between two platelets using different platelet activation states, and blockade of platelet receptors. The rupture force was found to increase proportionally to the degree of platelet activation, but reduced with blockade of specific platelet receptors. Quantification of single platelet-platelet interaction provides major perspectives for testing and improving biocompatibility of new materials; quantifying the effect of drugs on platelet function; and assessing the mechanical characteristics of acquired/inherited platelet defects. PMID:27146004

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

    OpenAIRE

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

    2013-01-01

    Background 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 associa...

  13. Papel da curva de agregação plaquetária no controle da antiagregação na prevenção secundária do acidente vascular cerebral isquêmico Platelet aggregation test: application in the control of antiplatelet aggregation in the secondary prevention of stroke

    Directory of Open Access Journals (Sweden)

    Patrícia Regina Piedade

    2003-09-01

    Full Text Available INTRODUÇÃO: O acidente vascular cerebral (AVC é atualmente a primeira causa de morte no Brasil. O risco de recorrência de AVC é de aproximadamente 30% em cinco anos. Agentes antiagregantes plaquetários são frequentemente prescritos para a prevenção de recorrência do AVC, porém sem um parâmetro laboratorial de ajuste terapêutico. OBJETIVO: Determinar a aplicabilidade da curva de agregação plaquetária, no controle do antiagregante, na prevenção secundária do acidente vascular cerebral isquêmico (AVCi. MÉTODO: Estudo retrospectivo de janeiro de 1990 a janeiro de 2001; foram analisados 189 pacientes com diagnóstico de AVCi acompanhados durante este período com curva de agregação plaquetária. Foram excluídos os portadores de doenças cardioembólicas. Consideraram-se hipoagregados os doentes com agregação plaquetária ativada pelo ADP e/ou pela adrenalina menor ou igual a 50%. Os doentes tiveram acompanhamento por 1 a 6 anos e a taxa de recorrência de AVCi foi comparada entre os normoagregados e os hipoagregados. RESULTADOS: Nove doentes apresentaram novo AVCi no período do seguimento. Entre os hipoagregados ocorreu 2,6% de recidiva e entre os normoagregados, 15,1% (0,03INTRODUCTION: Stroke is the leading cause of death in Brazil. The risk of suffering a recurrent stroke is around 30% in 5 years. Antiplatelet therapy has been frequently used to prevent recurrent strokes without laboratory control. OBJECTIVE: To determine the value of the platelet aggregation test in the control of antiplatelet aggregation in the secondary stroke prevention. METHOD: Retrospective study from January 1990 to January 2001 with 189 patients with stroke that were followed up during this period with platelet aggregation curve. Patients with cardioembolic disease were excluded. Low aggregation rates of platelet aggregation activated by ADP and/or epinephrine lower or equal to 50% were considered. Patients were followed up for a period from one

  14. 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.

  15. 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.

    Science.gov (United States)

    Sharma, Vivek; Sharma, Sarang; Dudeja, Pooja; Grover, Shibani

    2016-01-01

    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. PMID:27041904

  16. Hormonal contraception and platelet function.

    Science.gov (United States)

    Saleh, A A; Ginsburg, K A; Duchon, T A; Dorey, L G; Hirata, J; Alshameeri, R S; Dombrowski, M P; Mammen, E F

    1995-05-15

    73 healthy women (29 controls, 25 using OCs, and 19 using Norplant) were selected from the clinic population at North Oakland Medical Center for inclusion in this study after obtaining informed consent. Age, race, height, weight, blood pressure, and cigarette smoking were recorded for each subject. 12 patients were on monophasic OCs while 13 were on triphasic preparations. Both hormonal contraceptive groups had used their particular contraceptive for at least 3 months prior to blood drawing. Platelet tests were performed within 2 hours of sample collection: platelet counts (PLC) and mean platelet volume (MPV) were determined on an Automated Platelet Counter (Baker 810 Platelet Analyzer). Whole blood aggregation was performed on a platelet aggregometer (Chrono-Log, Model 550) using both ADP (ADP, 5 mM) and collagen (COLL, 2 mcg/ml) as inducing agents. Demographic differences were not significant (p 0.05) among the 3 treatment groups, whose average age was 25.3-25.8 years old. Furthermore, no significant differences (p 0.05) in platelet function were detected among controls or subjects receiving either oral contraceptives or Norplant, compared to control patients. The mean platelet counts (X 10/9/L) were 223 for OC users, 231 for Norplant users, and 232 for controls. The respective platelet aggregation (ADP, ohms) values were 12.5, 18.0, and 19.2 as well as (COLL, ohms) 35.6, 40.7, and 39.0. These results demonstrated that there is no evidence for altered platelet function, with the testing methods employed, in women using either Norplant or combination low dose oral contraceptives. To date, several studies have examined this issue, with contradictory reports about the effects of hormonal contraceptives in platelet function. After controlling for differences between various steroid preparations and other such confounding variables, some of these conflicting conclusions could be the result of a lack of uniformity among the methods used to evaluate platelet aggregation

  17. Role of platelets in allergic airway inflammation.

    Science.gov (United States)

    Idzko, Marco; Pitchford, Simon; Page, Clive

    2015-06-01

    Increasing evidence suggests an important role for platelets and their products (e.g., platelet factor 4, β-thromboglobulin, RANTES, thromboxane, or serotonin) in the pathogenesis of allergic diseases. A variety of changes in platelet function have been observed in patients with asthma, such as alterations in platelet secretion, expression of surface molecules, aggregation, and adhesion. Moreover, platelets have been found to actively contribute to most of the characteristic features of asthma, including bronchial hyperresponsiveness, bronchoconstriction, airway inflammation, and airway remodeling. This review brings together the current available data from both experimental and clinical studies that have investigated the role of platelets in allergic airway inflammation and asthma. It is anticipated that a better understanding of the role of platelets in the pathogenesis of asthma might lead to novel promising therapeutic approaches in the treatment of allergic airway diseases. PMID:26051948

  18. 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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Using flow cytometry, platelet-leukocyte aggregate (PLA) formation has previously been documented in dogs with a variety of systemic inflammatory disorders and immune-mediated haemolytic anaemia. Platelet activation and subsequent interaction between platelets and leukocytes are important for reg...

  20. Pseudo grey platelet syndrome--grey platelets due to degranulation in blood collected into EDTA.

    Science.gov (United States)

    Cockbill, S R; Burmester, H B; Heptinstall, S

    1988-10-01

    We have studied a woman with a history of mild bruising and bleeding, with a normal platelet count and normal clotting factors, who had platelets that appeared grey when stained and viewed under the microscope. Unlike the grey platelet syndrome, the abnormality was only evident when blood had been collected into EDTA and not when citrate or heparin was used as anticoagulant. This 'pseudo grey platelet syndrome' was associated with platelet dense body and alpha granule secretion with no aggregation and occurred on removal of extracellular Ca2+. We discovered that a plasma factor was responsible which could be an immunoglobulin but which is clearly different from the EDTA-sensitive antibodies which cause platelet aggregation and agglutination. We were not able to demonstrate a relationship between the mild bleeding tendency and the in vitro abnormality. PMID:3143601

  1. Metabolic Plasticity in Resting and Thrombin Activated Platelets

    OpenAIRE

    Ravi, Saranya; Chacko, Balu; Sawada, Hirotaka; Kramer, Philip A.; Johnson, Michelle S.; Benavides, Gloria A.; O’DONNELL, Valerie; Marques, Marisa B.; Darley-Usmar, Victor M.

    2015-01-01

    Platelet thrombus formation includes several integrated processes involving aggregation, secretion of granules, release of arachidonic acid and clot retraction, but it is not clear which metabolic fuels are required to support these events. We hypothesized that there is flexibility in the fuels that can be utilized to serve the energetic and metabolic needs for resting and thrombin-dependent platelet aggregation. Using platelets from healthy human donors, we found that there was a rapid throm...

  2. 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).

  3. Platelet scintigraphy in atherothrombotic disease

    International Nuclear Information System (INIS)

    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 PGI2 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 99mTc-labelled thrombus imaging agent, if thrombus imaging is to be considered for more generall use for patients with atherosclerosis. (author)

  4. The binding of fibrinogen to platelets in diabetes mellitus

    International Nuclear Information System (INIS)

    Platelets from diabetics are known to be more sensitive in vitro to a variety of aggregating agents, to produce more prostaglandin endoperoxides and thromboxane and to bind more 125I-fibrinogen than platelets from normal controls. Fibrinogen binding to platelets is a pre-requisite for platelet aggregation. Previous studies suggested a role for prostaglandins and/or thrombaxane A2 in the exposure of fibrinogen receptors on platelets. The present study compares fibrinogen binding to hyperaggregable platelets from diabetic patients and to normal platelets when prostaglandin/thromboxane formation is suppressed by aspirin. It was found that pre-treatment with aspirin reduced collagen or thrombin-induced binding to platelets from none-retinopathic diabetics to the values seen in controls. By contrast, aspirin did not normalize binding to platelets obtained from retinopathic diabetics. The combination of aspirin with apyrase (an ADP scavenger) almost completely inhibited binding and aggregation of platelets from normal controls or non-retinophatic diabetics exposed to collagen or thrombin, whereas it only partially affected binding and aggregation of platelets from retinopathics. By using a monoclonal antibody (B59.2) to the platelet receptor for fibrinogen, we determined that this receptor was quantitatively and qualitatively the same on platelets from normal controls and diabetics. We conclude that increased fibrinogen binding and hyperaggregability of platelets from none-retinopathic diabetics is related to their capacity to form more prostaglandin endoperoxides/thromboxane than normal platelets. In contrast, hyperaggregability and increased binding of platelets from retinopathics appear at least partly related to a mechanism independent of ADP release and thromboxane synthesis. (Author)

  5. 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.

  6. Platelet Count

    Science.gov (United States)

    ... or exertion Recovery from excess alcohol consumption and vitamin B12 and folate deficiency Rarely, thrombocytosis is caused by ... have bleeding problems, as the platelets may not function normally. This disorder is often associated with a ...

  7. Influence of shear stress on erythrocyte aggregation.

    Science.gov (United States)

    Kim, Jeong-Ho; Lee, Hoyoon; Lee, Byoung-Kwon; Shin, Sehyun

    2015-09-25

    Shear stress is known to induce platelet activation and aggregation. The red blood cell (RBC) aggregation test requires the application of shear stress for the cells to disaggregate for initialization. We tested the hypothesis that applying shear stress may activate platelets, which can influence RBC aggregation. The present study used a commercial microchip-based aggregometer (RheoSCan-AnD300) with a rotating stirrer for RBC disaggregation. Whole blood samples were exposed to different magnitudes of shear stress with various shearing times. As the rotational speed was increased up to 2800 rpm, the RBC aggregation index (AI) of the whole blood increased by up to 30% (p <  0.05), whereas that of the platelet-excluded blood samples did not show any apparent alteration. The AI also increased in proportion with the stirring time. The data suggest that high shear stress affects RBC aggregation through shear-induced platelet aggregation. PMID:26444600

  8. Dose-dependent platelet stimulation and inhibition induced by anti-PIA1 IgG

    International Nuclear Information System (INIS)

    The PIA1 antibody produces several clinically distinct and severe thrombocytopenias. Investigations have demonstrated divergent effects on platelet function; prior reports demonstrated inhibition, while a conflicting publication showed platelet activation. We have resolved this conflict using anti-PIA1 IgG produced by a patient with posttransfusion purpura. Relatively low concentrations stimulated platelet aggregation and release of adenosine triphosphate (ATP) whereas high concentrations inhibited platelet function, producing a thrombasthenia-like state. The number of molecules of platelet-associated IgG necessary to initiate aggregation and ATP release (2,086 +/- 556) or produce maximum aggregation (23,420 +/- 3,706) or complete inhibition (63,582 +/- 2654) were measured with a quantitative radiometric assay for bound anti-PIA1. Preincubation of platelets with high concentrations of PIA1 antibody inhibited platelet aggregation with 10 mumol/L adenosine diphosphate and blocked 125I-labeled fibrinogen platelet binding. Platelet activation with nonfibrinogen dependent agonist, 1 U/ml thrombin, was not inhibited by this high concentration of PIA1 IgG. In conclusion, anti-PIAI IgG produces (1) stimulation of platelet aggregation and ATP release that is initiated with 2000 molecules IgG per platelet and is associated with an increase of 125I-fibrinogen binding; (2) conversely, inhibition of platelet aggregation is observed with maximum antibody binding, 63,000 molecules IgG per platelet, and is mediated via a blockade of fibrinogen binding

  9. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    International Nuclear Information System (INIS)

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with 14C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A2 (TXA2) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more 14C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p 14C release: 1.5 +/- 0.5%, p 2 formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of 125I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA2 formation, the action of released ADP or increased thrombin binding

  10. Platelet Function Tests in Bleeding Disorders.

    Science.gov (United States)

    Lassila, Riitta

    2016-04-01

    Functional disorders of platelets can involve any aspect of platelet physiology, with many different effects or outcomes. These include platelet numbers (thrombocytosis or thrombocytopenia); changes in platelet production or destruction, or capture to the liver (Ashwell receptor); altered adhesion to vascular injury sites and/or influence on hemostasis and wound healing; and altered activation or receptor functions, shape change, spreading and release reactions, procoagulant and antifibrinolytic activity. Procoagulant membrane alterations, and generation of thrombin and fibrin, also affect platelet aggregation. The above parameters can all be studied, but standardization and quality control of assay methods have been limited despite several efforts. Only after a comprehensive clinical bleeding assessment, including family history, information on drug use affecting platelets, and exclusion of coagulation factor, and tissue deficits, should platelet function testing be undertaken to confirm an abnormality. Current diagnostic tools include blood cell counts, platelet characteristics according to the cell counter parameters, peripheral blood smear, exclusion of pseudothrombocytopenia, whole blood aggregometry (WBA) or light transmission aggregometry (LTA) in platelet-rich plasma, luminescence, platelet function analysis (PFA-100) for platelet adhesion and deposition to collagen cartridges under blood flow, and finally transmission electron microscopy to exclude rare structural defects leading to functional deficits. The most validated test panels are included in WBA, LTA, and PFA. Because platelets are isolated from their natural environment, many simplifications occur, as circulating blood and interaction with vascular wall are omitted in these assays. The target to reach a highly specific platelet disorder diagnosis in routine clinical management can be exhaustive, unless needed for genetic counseling. The elective overall assessment of platelet function disorder

  11. Platelet function in patients with a history of unexplained recurrent miscarriage who subsequently miscarry again.

    LENUS (Irish Health Repository)

    Dempsey, Mark Anthony

    2015-05-01

    This study was designed to evaluate platelet aggregation in pregnant women with a history of unexplained recurrent miscarriage (RM) and to compare platelet function in such patients who go on to have either another subsequent miscarriage or a successful pregnancy.

  12. 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; Bochsen, Louise; Johansson, Pär I

    2011-01-01

    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......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......-, COL-, and TRAP-test. The WB responses decreased at platelet concentration of ≤100 × 10(9)/L (all P <.03), except for heparin-TRAP (50 × 10(9)/L, P = .008) and citrate-ASPI (150 × 10(9)/L, P = .03). In general, WB samples demonstrated higher aggregation than PRP samples at platelet concentrations 200...

  13. 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; Bochsen, Louise; Johansson, Pär I

    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-test. The WB responses decreased at platelet concentration of ≤100 × 10(9)/L (all P <.03), except for heparin-TRAP (50 × 10(9)/L, P = .008) and citrate-ASPI (150 × 10(9)/L, P = .03). In general, WB samples demonstrated higher aggregation than PRP samples at platelet concentrations 200...

  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. PMID:26471595

  15. The effect of centrifugation speed and time on pre-analytical platelet activation

    DEFF Research Database (Denmark)

    Söderström, Anna C; Nybo, Mads; Nielsen, Christian; Vinholt, Pernille J

    2016-01-01

    . METHODS: Citrate- and EDTA-anticoagulated blood from healthy volunteers were centrifuged at 80-10,000 g for 5-15 min to prepare plasma and platelet-rich plasma. Pre-analytical platelet activation was assessed by flow cytometric measurement of platelet P-selectin (CD62p) expression. Blood cell counts, mean...... platelet volume (MPV), immature platelet fraction (IPF), and platelet distribution width (PDW) were measured. Platelet aggregation in platelet-rich plasma induced by arachidonic acid (AA), ADP or thrombin receptor activator peptide-6 (TRAP) was tested by 96-well aggregometry. RESULTS: The median percentage......%-15%), p<0.001. Platelet count in plasma samples decreased with increasing speed but platelets were only completely removed if plasma was re-centrifuged. In platelet-rich plasma, increasing centrifugation speed significantly increased platelet yield but decreased contamination from other blood cells...

  16. A role for prostaglandins and thromboxanes in the exposure of platelet fibrinogen receptors.

    OpenAIRE

    Bennett, J.S.; Vilaire, G; Burch, J W

    1981-01-01

    Exposure of fibrinogen receptors by a variety of agonists is a prerequisite for platelet aggregation. Because the synthesis of prostaglandins and thromboxane A2 also occurs during platelet aggregation we wondered whether these agents participate in the exposure of platelet fibrinogen receptors. Therefore, we measured the binding of human 125I-fibrinogen to gel-filtered normal human platelets after prostaglandin and thromboxane synthesis had been inhibited by aspirin or indomethacin. The fibri...

  17. Ultraviolet irradiation effect on human platelet function

    International Nuclear Information System (INIS)

    Treatment of human blood platelets with ultraviolet light (uv) results in changes of several physiological functions. When uv-treated platelets are stirred in the presence of fibrinogen and calcium ions aggregation occurs. The amount of aggregation is dependent upon the uv dosage and wavelength, the fibrinogen concentration and the calcium concentration. Maximum aggregation occurs with a 250 joule/m2 dosage at 245 nm wavelength in the presence of 0.5 mg/ml fibrinogen and 2 mM calcium ion. Aggregation induced by uv is partially inhibited by apyrase or by metabolic inhibitors. Hirudin, a potent inhibitor of thrombin action, did not inhibit uv-induced aggregation. Pretreatment with uv decreases the ability of platelets to support clot retraction. An action spectrum for the effect has maxima at 210 nm and at 280 nm indicating the chromophore is a protein containing aromatic amino acids. Dosages greater than 120 seconds of exposure to a Hanovia High-Pressure Quartz Mercury-Vapor Lamp render the platelets incapable of supporting retraction of fibrin clots induced by thrombin. Irradiation with 250 nm uv has the ability to stimulate retraction of fibrin clots induced by reptilase. Thrombin-mediated platelet functions, including binding, release and aggregation are also inhibited by uv irradiation. The number of binding sites per platelet is reduced by 43 percent with a 90 second dose of uv. For the same dose, the total amount of serotonin released is decreased from 81 percent to 41 percent while the thrombin-induced aggregation is completely inhibited. An action spectra contains two maxima, at 245 nm and 280 nm. The effect of uv is compared with the effect of dithiothreitol (DTT) as a test of the hypothesis that uv-induced aggregation is mediated by disulfide bond disruption

  18. Regulation of fibrinogen receptor expression on human platelets

    International Nuclear Information System (INIS)

    Platelet aggregation requires the binding of fibrinogen to specific receptors on the plasma membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The authors have developed a monoclonal anti-IIb-IIIa antibody (PAC-1) that binds only to stimulated platelets and only in the presence of Ca. In order to better understand the steps leading to platelet aggregation, the authors used radiolabeled PAC-1 and fibrinogen to examine the effect of the α2-adrenergic agonist, epinephrine, on the expression and function of the fibrinogen receptor. The addition of epinephrine to unstirred platelets caused and immediate increase in PAC-1 and fibrinogen binding that was associated with platelet aggregation once the platelets were stirred. Even after prolonged incubation of the platelets with epinephrine, fibrinogen receptor expression could be reversed by adding EGTA, PGl2, or the α2-adrenergic antagonist, phentolamine. When unstirred platelets were exposed to epinephrine for more than 10 min, the extent of aggregation caused by subsequent stirring was decreased by 70%. Surprisingly, these desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due to a decrease in fibrinogen receptor expression or function. These studies demonstrate that: (1) fibrinogen receptor expression is dependent on extracellular CA; (2) induction of the fibrinogen receptor by epinephrine requires the continued presence of the agonist; and (3) prolonged stimulation of the platelet by epinephrine can lead to a reduced aggregation response by a mechanism that does not involve a loss of either fibrinogen recepor expression or fibrinogen binding

  19. Resveratrol preserves the function of human platelets stored for transfusion.

    Science.gov (United States)

    Lannan, Katie L; Refaai, Majed A; Ture, Sara K; Morrell, Craig N; Blumberg, Neil; Phipps, Richard P; Spinelli, Sherry L

    2016-03-01

    Stored platelets undergo biochemical, structural and functional changes that lead to decreased efficacy and safety of platelet transfusions. Not only do platelets acquire markers of activation during storage, but they also fail to respond normally to agonists post-storage. We hypothesized that resveratrol, a cardioprotective antioxidant, could act as a novel platelet storage additive to safely prevent unwanted platelet activation during storage, while simultaneously preserving normal haemostatic function. Human platelets treated with resveratrol and stored for 5 d released less thromboxane B2 and prostaglandin E2 compared to control platelets. Resveratrol preserved the ability of platelets to aggregate, spread and respond to thrombin, suggesting an improved ability to activate post-storage. Utilizing an in vitro model of transfusion and thromboelastography, clot strength was improved with resveratrol treatment compared to conventionally stored platelets. The mechanism of resveratrol's beneficial actions on stored platelets was partly mediated through decreased platelet apoptosis in storage, resulting in a longer half-life following transfusion. Lastly, an in vivo mouse model of transfusion demonstrated that stored platelets are prothrombotic and that resveratrol delayed vessel occlusion time to a level similar to transfusion with fresh platelets. We show resveratrol has a dual ability to reduce unwanted platelet activation during storage, while preserving critical haemostatic function. PMID:26683619

  20. Procoagulant activity on platelets adhered to collagen or plasma clot.

    Science.gov (United States)

    Ilveskero, S; Siljander, P; Lassila, R

    2001-04-01

    In a new 2-stage assay of platelet procoagulant activity (PCA), we first subjected gel-filtered platelets to adhesion on collagen (as a model of primary hemostasis) or plasma clots (as a model of preformed thrombus) for 30 minutes, and then the adherent platelets were supplemented with pooled, reptilase-treated, diluted plasma. Defibrinated plasma provided coagulation factors for assembly on platelet membranes without uncontrolled binding of thrombin to fibrin(ogen). Platelet adhesion to both surfaces showed modest individual variation, which increased at platelet densities that allowed aggregation. However, adhesion-induced PCA varied individually and surface-independently >3-fold, suggesting a uniform platelet procoagulant mechanism. Permanently adhered platelets showed markedly enhanced PCA when compared with the platelet pool in suspension, even after strong activation. The rate of thrombin generation induced by clot-adherent platelets was markedly faster than on collagen-adherent platelets during the initial phase of coagulation, whereas collagen-induced PCA proceeded slowly, strongly promoted by tissue thromboplastin. Therefore at 10 minutes, after adjustment for adhered platelets, collagen supported soluble thrombin formation as much as 5 times that of the thrombin-retaining clots. Activation of platelets by their firm adhesion was accompanied by formation of microparticles, representing about one third of the total soluble PCA. Collagen-adhered platelets provide soluble thrombin and microparticles, whereas the preformed clot serves to localize and accelerate hemostasis at the injury site, with the contribution of retained thrombin and microparticles. PMID:11304482

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

    International Nuclear Information System (INIS)

    Platelet aggregation has been most commonly studied in vitro by measuring increases in light transmission as platelets aggregate in PRP. Recently, an electrical impedance method for measuring platelet aggregation has been introduced. This method can be used with either PRP or whole blood and measures an increase in impedance across electrodes placed in the blood samples as platelets accumulate on them. We have compared the results obtained by the two methods, using ADP and collagen as aggregating agents, and also have measured the secretion of platelet ATP simultaneously. Although the aggregometry results were similar, recordings obtained by the electrical method did not distinguish two waves of platelet aggregation or correlate with secretion as well as recordings obtained by the optical method. When PGI2 or PGE1 was added to the PRP, both the rate and extent of the increase in light transmittance were inhibited, but the main effect on the increase in impedance was a decrease in its rate and not in its extent. Increases in impedance and secretion of ATP were also measured in whole blood after the platelets had been labeled with a 125I-containing antibody specific for platelet surface glycoproteins. It appeared that the increases in impedance lagged several minutes behind the formation of platelet aggregates and the secretion of platelet ATP. It is suggested that there are advantages and disadvantages to both methods of measurement of platelet aggregation and that the parameters being measured must be clearly understood to properly interpret the results

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

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta; Hagedorn, Ina; Eliautou, Sandra; Bender, Markus; Wu, Xunwei; Lanza, Francois; Gachet, Christian; Brakebusch, Cord; Nieswandt, Bernhard

    2010-01-01

    (ADP)/adenosine triphosphate (ATP) content, increased aggregation at low agonist concentrations, and enhanced aggregate formation on collagen under flow. In vivo, lack of Cdc42 resulted in faster occlusion of ferric chloride-injured arterioles. The life span of Cdc42-deficient platelets was markedly...

  3. Functional aspects of blood platelets in irradiated burros

    International Nuclear Information System (INIS)

    In irradiated burros (Equus asinus), a delayed clinical syndrome characterized by a depletion of megakarocytes and platelets has been observed. To clarify the cause of this syndrome, the functional abilities of platelets in 7 irradiated and 3 control burros were studied in vitro. The irradiated burros were survivors (> 18 years) of total-body exposures to near-lethal doses of γ-radiation. Burro platelet aggregability induced with adenosine diphosphate and thrombin, and with a complex stimulator from burro aortas, was determined by means of a self-calibrating aggregometer. Data indicated that the aggregation responsiveness to adenosine diphosphate and thrombin of platelets from surviving irradiated and unirradiated burros is not defective. An extractible collagen-like stimulator of platelet aggregation was discovered in the aorta of a burro that had survived > 24 years after exposure to a total-body dose of 545 roentgens (R) of tantalum-182 γ-radiation. The platelet-aggregating ability of this stimulator from the vessel wall of the irradiated burro was nearly fourfold greater than that from the aorta of an unirradiated control. Perhaps a delayed radiation effect could be the cause of this vascular agent's high platelet-aggregating ability and could lead to a clinical syndrome marked by depletion of megakaryocytes and platelets

  4. A computerized multichannel platelet aggregometer system.

    Science.gov (United States)

    Kuzara, D; Zoltan, B J; Greathouse, S L; Jordan, C W; Kohler, C A

    1986-08-01

    Commercially available instrumentation for conducting platelet aggregation studies in clinical and research laboratories consists of one-, two-, or four-channel aggregometers used in conjunction with strip chart recorders. These instruments have limited utility in large-scale drug screening and evaluation of the mode of action of drugs or in the clinical diagnosis of platelet disorders. A new instrument, a computerized multichannel aggregometer system (CMPAS) has been developed to collect, display, and analyze platelet aggregation data. The system is comprised of a 24-channel Born-type aggregometer, interfaced to a Rockwell AIM-65 microcomputer through an analogue-to-digital converter and an Epson dot-matrix printer. Each channel is individually calibrated, and aggregation data can be collected on up to 24 different platelet-rich plasma samples simultaneously. Conversational programs written in BASIC prompt the user for the addition of agonists and inhibitors. The tracings for each channel are displayed simultaneously, and a program automatically analyzes the data to generate the following parameters: baseline optical density, maximum aggregation response, positive and negative slopes, time to peak aggregation, and percentage response. Computerized multichannel aggregometer system data outputs are comparable to data generated by a standard Chronolog aggregometer unit. The advantages of the system include multichannel capability, simultaneous display of all channels allowing relative comparisons between control and experimental groups, and time savings and improved efficiency in conducting and analyzing aggregation experiments. PMID:3755779

  5. Does bipolar pacemaker current activate blood platelets?

    DEFF Research Database (Denmark)

    Gjesdal, Grunde; Hansen, Annebirthe Bo; Brandes, Axel

    2009-01-01

    platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets......, to the depolarizing current. Platelet activation may ensue, resulting in aggregation, release reaction, and contraction. In contrast, a unipolar pacemaker system will not depolarize blood, but transmit current directly into the myocardium, and the current afterward passes through other tissues before...

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

    Directory of Open Access Journals (Sweden)

    Ye-Ming Lee

    2012-01-01

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

  7. Platelet content of nitric oxide synthase 3 phosphorylated at Serine 1177 is associated with the functional response of platelets to aspirin.

    Directory of Open Access Journals (Sweden)

    Javier Modrego

    Full Text Available OBJECTIVE: To analyse if platelet responsiveness to aspirin (ASA may be associated with a different ability of platelets to generate nitric oxide (NO. PATIENTS/METHODS: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26 and ASA-resistant (n = 24 using a platelet functionality test (PFA-100. RESULTS: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3 was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2 isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786 → C in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser(1177, an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177 phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018 of NOS3 phosphorylation at Ser(1177. On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177. During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets. CONCLUSIONS: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177.

  8. Vasopressin-induced aggregation of platelets

    Czech Academy of Sciences Publication Activity Database

    Pencheva, N.; Penev, M.; Mladenova, A.; Barthová, J.; Barth, Tomislav

    1999-01-01

    Roč. 6, č. 1 (1999), s. PP036. [Congress of Balkan Clinical Laboratory Federation /7./. 04.11.1999-07.11.1999, Antalya] R&D Projects: GA MPO PP-Z1/24/99 Institutional research plan: CEZ:AV0Z4055905 Subject RIV: CE - Biochemistry

  9. Metabolic plasticity in resting and thrombin activated platelets.

    Directory of Open Access Journals (Sweden)

    Saranya Ravi

    Full Text Available Platelet thrombus formation includes several integrated processes involving aggregation, secretion of granules, release of arachidonic acid and clot retraction, but it is not clear which metabolic fuels are required to support these events. We hypothesized that there is flexibility in the fuels that can be utilized to serve the energetic and metabolic needs for resting and thrombin-dependent platelet aggregation. Using platelets from healthy human donors, we found that there was a rapid thrombin-dependent increase in oxidative phosphorylation which required both glutamine and fatty acids but not glucose. Inhibition of fatty acid oxidation or glutamine utilization could be compensated for by increased glycolytic flux. No evidence for significant mitochondrial dysfunction was found, and ATP/ADP ratios were maintained following the addition of thrombin, indicating the presence of functional and active mitochondrial oxidative phosphorylation during the early stages of aggregation. Interestingly, inhibition of fatty acid oxidation and glutaminolysis alone or in combination is not sufficient to prevent platelet aggregation, due to compensation from glycolysis, whereas inhibitors of glycolysis inhibited aggregation approximately 50%. The combined effects of inhibitors of glycolysis and oxidative phosphorylation were synergistic in the inhibition of platelet aggregation. In summary, both glycolysis and oxidative phosphorylation contribute to platelet metabolism in the resting and activated state, with fatty acid oxidation and to a smaller extent glutaminolysis contributing to the increased energy demand.

  10. Incidence of platelet dysfunction by thromboelastography-platelet mapping in children supported with ECMO: A Pilot Retrospective Study.

    Directory of Open Access Journals (Sweden)

    Arun eSaini

    2016-01-01

    Full Text Available Background: Bleeding complications are common and decrease the odds of survival in children supported with extracorporeal membrane oxygenation (ECMO. The role of platelet dysfunction on ECMO-induced coagulopathy and resultant bleeding complications is not well understood. The primary objective of this pilot study was to determine the incidence and magnitude of platelet dysfunction according to thromboelastography (TEG®-platelet mapping (PM testing. Methods: Retrospective chart review of children <18 years old who required ECMO at a tertiary level hospital. We collected TEG®-PM and conventional coagulation tests data. We also collected demographic, medications, blood products administered, and clinical outcome data. We defined severe platelet dysfunction as less than 50 % aggregation in response to an agonist. Results: We identified 24 out of 46 children on ECMO, who had TEG®-PM performed during the study period. We found the incidence of severe bleeding was 42%, and mortality was 54% in our study cohort. In all samples measured, severe qualitative platelet dysfunction was more common for adenosine diphosphate (ADP-mediated aggregation (92% compared to arachidonic acid (AA-mediated aggregation (75%, (p=0.001. Also, ADP-mediated percent of platelet aggregation was significant lower than AA-mediated platelet aggregation (15% [IQR 2.8-48] vs 49% [IQR 22-82.5], p<0.001. There was no difference in kaolin-activated heparinase TEG® parameters between the bleeding group and the non-bleeding group. Only absolute platelet count and TEG®-PM had increased predictive value on receiver operating characteristics analyses for severe bleeding and mortality compared to ACT. Conclusions: We found frequent and severe qualitative platelet dysfunction on TEG®-PM testing in children on ECMO. Larger studies are needed to determine if the assessment of qualitative platelet function by TEG®-PM can improve prediction of bleeding complications for children on ECMO.

  11. Salvianolic acid B inhibits platelets as a P2Y12 antagonist and PDE inhibitor: evidence from clinic to laboratory.

    Science.gov (United States)

    Liu, Lei; Li, Jian; Zhang, Yan; Zhang, Shenghui; Ye, Jianqin; Wen, Zhichao; Ding, Jianping; Kunapuli, Satya P; Luo, Xinping; Ding, Zhongren

    2014-10-01

    Salviae miltiorrhiza (Danshen) has been used for thousands of years in China and some other Asian countries to treat atherothrombotic diseases. Salvianolate which consists of three water-soluble ingredients purified from Salviae miltiorrhiza, has been approved by Chinese SFDA to treat coronary artery disease. So far, there is no evidence clearly showing the clinical efficiency of salvianolate and the underlying mechanism. This study is to evaluate the effects of salvianolate on platelets in patients with acute coronary syndrome and explore the underlying mechanism. We evaluated the effects of salvianolate on platelets in patients with acute coronary syndrome by measuring ADP-induced PAC-1 binding and P-selectin expression on platelets. Salvianolate significantly potentiated the antiplatelet effects of standard dual antiplatelet therapy. We also investigated the antiplatelet effects of salvianolatic acid B (Sal-B), the major component which composes 85% of salvianolate. Sal-B inhibits human platelet activation induced by multiple agonists in vitro by inhibiting phosphodiesterase (PDE) and antagonizing P2Y12 receptor. For the first time, we show the antiplatelet efficiency of salvianolate in ACS patients undergoing treatment with clopidogrel plus aspirin, and demonstrate that Sal-B, the major component of salvianolate inhibits human platelet activation via PDE inhibition and P2Y12 antagonism which may account for the clinical antiplatelet effects of salvianolate. Our results suggest that Sal-B may substitute salvianolate for clinical use. PMID:25077998

  12. 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...

  13. Platelets and galectins

    OpenAIRE

    Schattner, Mirta

    2014-01-01

    A major function of platelets is keeping the vascular system intact. Platelet activation at sites of vascular injury leads to the formation of a hemostatic plug. Activation of platelets is therefore crucial for normal hemostasis; however, uncontrolled platelet activation may also lead to the formation of occlusive thrombi that can cause ischemic events. Although they are essential for proper hemostasis, platelet function extends to physiologic processes such as tissue repair, wound remodeling...

  14. Current and emerging approaches for evaluating platelet disorders.

    Science.gov (United States)

    Podda, G; Femia, E A; Cattaneo, M

    2016-05-01

    Platelets play a central role in physiological hemostasis and also in pathological thrombosis. It is well established that congenital or acquired abnormalities of platelet function are associated with a heightened risk of bleeding of variable severity and excessive hemorrhage after surgery or trauma. Several kinds of different platelet function tests have been developed over the years to identify or diagnose platelet function disorders. The use of these tests for the assessment of thrombotic risk or for monitoring the effects of drugs inhibiting platelet function is not well established. Light transmission aggregometry (LTA) is the gold standard for the study of patients with defects of platelet function. Its results are affected by several pre-analytical and analytical variables. The Subcommittee on Platelet Physiology of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis published official guidelines for the standardization of the variables affecting LTA, which should be followed to harmonize the procedures across different laboratories worldwide. The lumi-aggregometer, a modification of LTA that measures platelet secretion in parallel with aggregation, is preferable to LTA for diagnosing inherited defects of platelet function, because it is more sensitive to the most common disorders, which are characterized by abnormalities of platelet secretion. LTA (or lumi-aggregometry) is useful as a first screening test of patients with the clinical suspicion of defects of platelet function, because it helps to provide an interim diagnostic hypothesis, which can then be confirmed or discounted using appropriate and specific tests. PMID:27426860

  15. Cigarette smoking inhibits the anti-platelet activity of aspirin in patients with coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    LI Wei-ju; ZHANG Hong-yin; MIAO Cheng-long; TANG Ri-bo; DU Xin; SHI Ji-hui; MA Chang-sheng

    2011-01-01

    Objective Tobacco smoking results in increased platelet aggregability, which suggests that low-dose aspirin used in common clinical practice may not effectively inhibit platelet activity in smokers with coronary heart disease (CHD). This review was performed to assess the effect of aspirin on platelet aggregation in patients with CHD.Data sources We performed an electronic literature search of MEDLINE (starting from the beginning to March 15, 2009)using the term "smoking" or "tobacco" paired with the following: "platelet", "aspirin" or "coronary heart disease".Study selection We looked for review articles regarding the effect of tobacco smoking on platelet activity and on the anti-platelet efficacy of aspirin in healthy people and patients with CHD. The search was limited in "core clinical journal".In total, 1321 relevant articles were retrieved, and 36 articles were ultimately cited.Results Tobacco smoking results in increased platelet aggregability, which can be inhibited by low-dose aspirin in the healthy population. However, in patients with CHD, the increased platelet aggregability can not be effectively inhibited by the same low-dose of aspirin. A recent study indicated that clopidogrel or an increased dose of aspirin can effectively inhibit the increased platelet aggregability induced by tobacco smoking in patients with CHD.Conclusions It is important for patients with CHD to quit smoking. For the current smoker, it may be necessary to take larger doses of aspirin than normal or take an adenosine diphosphate receptor inhibitor along with aspirin to effectively inhibit the increased platelet activity.

  16. Aggregation activity of blood formed elements in patients with type 1 and type 2 diabetes mellitus

    OpenAIRE

    Boris Il'ich Kuznik; Yuriy Antonovich Vitkovskiy; Marina Yur'evna Zakharova; Natal'ya Nikolaevna Klyuchereva; Ol'ga Sergeevna Rodnina; Aleksey Vladimirovich Solpov

    2012-01-01

    Aims. To assess differences in blood formed elements aggregation activity in patients with type 1 (T1) and type 2 (T2) diabetes mellitus (DM). Materials and methods. We studied blood samples from 88 patients with T1 and T2 DM. Platelet aggregation activity was assessed by means of «Biola» aggregometer; we also determined platelet-lymphocyte and leucocyte-erythrocyte adhesion intensity. Results. We show that spontaneous platelet aggregation is markedly increased in patients with T1...

  17. In vitro effect of the herbicide glyphosate on human blood platelet aggregation and coagulation Efeito in vitro do herbicida glifosato na agregação plaquetária e coagulação sanguínea em humanos

    Directory of Open Access Journals (Sweden)

    Teresinha de Jesus C. Neiva

    2010-01-01

    Full Text Available Glyphosate [N-(phosphonomethyl-glycine] is a broad-spectrum, non-selective, post-emergence herbicide that is extensively used in agriculture. Published data referring to the effects of this product on human health are contradictory. We showed previously that long-term treatment of rats with low doses of Glyphosate-Biocarb® may induce hepatic histological changes and bleeding without decreasing platelet counts. The aim of the current study was to investigate, in vitro, the effect of glyphosate on human blood platelet aggregation and coagulation. Materials and methods: Platelet aggregation was determined in the platelet-rich plasma using the agents: 6µM-adenosine diphosphate, 6µM-epinephrine and 4µg/mL-collagen. Pretreatment with 500µg/mL glyphosate showed significant hypofunction of the three aggregating agents. The inhibitory effect was dose-dependent at concentrations from 50 to 500 µg/mL. The release of ATP was lower for glyphosate-treated platelets after stimulation by collagen. On the other hand, glyphosate did not promote any inhibitory effects on prothrombin time, thromboplastin time and thrombin time. In conclusion, the results demonstrate that glyphosate promotes changes in the platelet metabolism with an inhibitory effect on primary hemostasis.O glifosato [N-(phosphonomethyl-glycine] é um herbicida pós-emergente não seletivo de amplo espectro muito utilizado na agricultura. Dados da literatura referentes aos efeitos desse produto na saúde humana são contraditórios. Em estudos prévios demonstramos que ratos previamente tratados com glifosato apresentavam lesões hepáticas e sangramento sem alterações quantitativas de plaquetas. O objetivo do presente estudo é investigar os efeitos in vitro do glifosato (GP na agregação plaquetária e coagulação sanguínea em humanos. A agregação plaquetária foi determinada em plasma rico em plaquetas (PRP usando os agentes adenosina difosfato (ADP 6µM, epinefrina 6µM e col

  18. Platelets and infections—complex interactions with bacteria

    Directory of Open Access Journals (Sweden)

    Hind eHAMZEH-COGNASSE

    2015-02-01

    Full Text Available Platelets can be considered sentinels of vascular system due to their high number in the circulation and to the range of functional immunoreceptors they express. Platelets express a wide range of potential bacterial receptors, including complement receptors, FcγRII, Toll-Like Receptors but also integrins conventionally described in the hemostatic response, such as GPIIb-IIIa or GPIb. Bacteria bind these receptors either directly, or indirectly via fibrinogen, fibronectin, the first complement C1q, the von Willebrand Factor, etc. The fate of platelet bound bacteria is questioned. Several studies reported the ability of activated platelets to internalize bacteria such as Staphylococcus aureus or Porphyromonas gingivalis, though there is no clue on what happens thereafter. Are they sheltered from the immune system in the cytoplasm of platelets or are they lysed? Indeed, while the presence of phagolysosome has not been demonstrated in platelets, they contain antimicrobial peptides that were shown to be efficient on S. aureus. Besides, the fact that bacteria can bind to platelets via receptors involved in hemostasis suggests that they may induce aggregation; this has indeed been described for Streptococcus sanguinis, S. epidermidis or C. pneumoniae. On the other hand, platelets are able to display an inflammatory response to an infectious triggering. We, and others, have shown that platelet release soluble immunomodulatory factors upon stimulation by bacterial components. Moreover, interactions between bacteria and platelets are not limited to only these two partners. Indeed, platelets are also essential for the formation of Neutrophil Extracellular Traps by neutrophils, resulting in bacterial clearance by trapping bacteria and concentrating antibacterial factors but in enhancing thrombosis. In conclusion, the platelet-bacteria interplay is a complex game; its fine analysis is complicated by the fact that the inflammatory component adds to the

  19. Characterization of multiple platelet activation pathways in patients with bleeding as a high-throughput screening option: use of 96-well Optimul assay

    OpenAIRE

    Lordkipanidzé, Marie; Lowe, Gillian C.; Kirkby, Nicholas S.; Chan, Melissa V.; Lundberg, Martina H.; Morgan, Neil V.; Bem, Danai; Nisar, Shaista P.; Leo, Vincenzo C.; Jones, Matthew L.; Warner, Timothy D.; Watson, Steve P.; Mumford, Andrew D.; Mundell, Stuart J.; Gissen, Paul

    2014-01-01

    The Optimul 96-well platelet aggregation assay has high levels of sensitivity and specificity for detecting platelet defects.The requirement for a small volume of blood, straightforward nature, and speed make Optimul a promising screening test in bleeding patients.

  20. Estudo comparativo entre agregação plaquetária por turbidimetria e impedância elétrica em pacientes sob terapia antiplaquetária à base de ácido acetilsalicílico Comparative study of platelet aggregation by turbidimetric and impedance methods in patients under acetylsalicylic acid antiplatelet therapy

    Directory of Open Access Journals (Sweden)

    Leonardo Lorenzo da Silva

    2010-01-01

    Full Text Available INTRODUÇÃO: A hiperagregação (agregação excessiva das plaquetas pode causar a formação de um trombo e a posterior oclusão dos vasos sanguíneos levando à isquemia. Esse fenômeno é responsável por doenças isquêmicas cardiovasculares, como angina pectoris e aterosclerose, bem como outras formas de isquemia, como o acidente vascular cerebral. Visando diminuir a função das plaquetas para reduzir a formação de trombos, o ácido acetilsalicílico vem sendo utilizado para tratamento antitrombótico, com diversos estudos mostrando sua eficácia. Dessa forma faz-se mister o uso de uma ferramenta laboratorial para o monitoramento da efetividade do tratamento, o que é feito por meio do teste de agregação plaquetária. O objetivo desse estudo foi comparar duas metodologias para esse exame (impedância elétrica e turbidimetria em relação a trinta pacientes adultos de ambos os sexos em uso do fármaco. CONCLUSÃO: Os resultados mostraram uma boa correlação entre os métodos, possibilitando o uso concomitante de ambas as técnicas em laboratórios clínicos de rotina.INTRODUCTION: Hyperaggregation of platelets can cause the formation of thrombi and subsequent occlusion of blood vessels leading to ischemia. This phenomenon can be responsible for ischemic cardiovascular diseases such as angina pectoris and atherosclerosis as well as other forms of ischemia such as stroke. To decrease platelet function and reduce the formation of thrombi, acetylsalicylic acid has been used for antithrombotic treatment, with several studies showing its effectiveness. Therefore it is necessary to use a laboratory tool to monitor the effectiveness of treatment, which is achieved through laboratory testing of platelet aggregation. The aim of this study was to compare two different methods (impedance and turbidimetry to test platelet aggregation in 30 adult patients of both genders taking acetylsalicylic acid. CONCLUSION: The results show that there is a

  1. 血小板microRNAs在先天性心脏病患儿中输血导致的血小板激活作用研究%Impact of packed red blood cell transfusion on platelet activation and aggrega-tion in pediatric patients with cardiac disease

    Institute of Scientific and Technical Information of China (English)

    苗晓蕾; 王旭; 刘晋萍; 崔勇丽; 赵明霞; 冯正义; 赵举; 龙村; 李守军; 晏馥霞

    2015-01-01

    Objective The aim of this study is to observe the impact of packed RBC transfusion on platelet activation and ag⁃gregation in vitro in pediatric patients with cardiac disease and to clarity whether circulating platelet microRNAs could be serve as a new indicator of platelet activation. Methods One hundred infant patients were randomly divided into 2 groups, transfusion group and non-transfusion group. Each group has 50 patients. In vitro transfusions were performed by the addition of RBC obtained from transfusion packs into fresh whole blood with a ratio about 1:4 (0.5 ml of RBC mixed with 1.8 ml of whole blood). After 30 min, the expression of P-selectin and the content of platelet microparticle (PMP) were tested by flow cytometry. Light transmission aggregometry was per⁃formed to determine the platelet aggregation. The expression levels of four kinds of circulation platelet microRNAs were detected by Taq⁃man quantitative real-time PCR. Results There were no significant difference in the baseline hemoglobin level between the two groups ( P>0. 05 ) . After RBC transfusion, the Hb level was elevated by 23 ± 6 g/L. Compared with non-transfusion group, platelet aggregation in transfusion group was significantly increased( P<0.05).Platelet activation was also increased by transfusion as confirmed by the elevation of P-selectin and PMP expressions induced by 20μM ADP. Similar results were found with the four kinds of circulat⁃ing platelet microRNAs ( P<0.05) . In the non-transfusion group, the levels of four kinds of microRNAs in the cyanotic subgroup were significantly elevated than the acyanotic subgroup( P<0.05) . Conclusion RBC transfusion increases in vitro platelet activation in pe⁃diatric patients with cardiac disease, providing a possible explanation for the increase in recurrent ischemic event and mortality reported after RBC transfusion in clinical practice. Circulation platelet microRNAs may serve as a new marker of platelet activation.%目的:

  2. Inhibition of platelet thromboxane formation and phosphoinositides breakdown by osthole from Angelica pubescens.

    Science.gov (United States)

    Ko, F N; Wu, T S; Liou, M J; Huang, T F; Teng, C M

    1989-11-24

    Osthole, isolated from Chinese herb Angelica pubescens, inhibited platelet aggregation and ATP release induced by ADP, arachidonic acid, PAF, collagen, ionophore A23187 and thrombin in washed rabbit platelets. It showed a weak activity in platelet-rich plasma. Osthole inhibited the thromboxane B2 formation caused by arachidonic acid, collagen, ionophore A23187 and thrombin in washed platelets, and also the thromboxane B2 formation caused by the incubation of lysed platelet homogenate with arachidonic acid. The generation of inositol phosphates in washed platelets caused by collagen, PAF and thrombin was suppressed by osthole. These data indicate that the inhibitory effect of osthole on platelet aggregation and release reaction was due to the inhibition of thromboxane formation and phosphoinositides breakdown. PMID:2556815

  3. Thrombin-Mediated Platelet Activation of Lysed Whole Blood and Platelet-Rich Plasma: A Comparison Between Platelet Activation Markers and Ultrastructural Alterations.

    Science.gov (United States)

    Augustine, Tanya N; van der Spuy, Wendy J; Kaberry, Lindsay L; Shayi, Millicent

    2016-06-01

    Platelet ultrastructural alterations representing spurious activation have been identified in pathological conditions. A limitation of platelet studies is that sample preparation may lead to artifactual activation processes which may confound results, impacting the use of scanning electron microscopy as a supplemental diagnostic tool. We used scanning electron microscopy and flow cytometry to analyze platelet activation in platelet-rich plasma (PRP) and whole blood (WB) samples. PRP generated using a single high g force centrifugation, and WB samples treated with a red blood cell lysis buffer, were exposed to increasing concentrations of the agonist thrombin. Platelets in lysed WB samples responded to thrombin by elevating the activation marker CD62p definitively, with corresponding ultrastructural changes indicating activation. Conversely, CD62p expression in PRP preparations remained static. Ultrastructural analysis revealed fully activated platelets even under low concentration thrombin stimulation, with considerable fibrin deposition. It is proposed that the method for PRP production induced premature platelet activation, preventable by using an inhibitor of platelet aggregation and fibrin polymerization. Nevertheless, our results show a definitive correspondence between flow cytometry and scanning electron microscopy in platelet activation studies, highlighting the potential of the latter technique as a supplemental diagnostic tool. PMID:27329313

  4. Platelet Dysfunction in Patients with Chronic Myeloid Leukemia: Does Imatinib Mesylate Improve It?

    Directory of Open Access Journals (Sweden)

    Olga Meltem Akay

    2016-05-01

    Full Text Available Objective: The aim of this study was to investigate the effects of imatinib mesylate on platelet aggregation and adenosine triphosphate (ATP release in chronic myeloid leukemia patients. Materials and Methods: Platelet aggregation and ATP release induced by 5.0 mM adenosine diphosphate, 0.5 mM arachidonic acid, 1.0 mg/ mL ristocetin, and 2 µg/mL collagen were studied by whole blood platelet lumi-aggregometer in 20 newly diagnosed chronic myeloid leukemia patients before and after imatinib mesylate treatment. Results: At the time of diagnosis, 17/20 patients had abnormal platelet aggregation results; 8 (40% had hypoactivity, 6 (30% had hyperactivity, and 3 (15% had mixed hypo- and hyperactivity. Repeat platelet aggregation studies were performed after a mean of 19 months (min: 5 months-max: 35 months in all patients who received imatinib mesylate during this period. After therapy, 18/20 (90% patients had abnormal laboratory results; 12 (60% had hypoactive platelets, 4 (20% had mixed hypo- and hyperactive platelets, and 2 (10% had hyperactive platelets. Three of the 8 patients with initial hypoactivity remained hypoactive, while 2 developed a mixed picture, 2 became hyperactive, and 1 normalized. Of the 6 patients with initial hyperactivity, 4 became hypoactive and 2 developed a mixed pattern. All of the 3 patients with initial hypo- and hyperactivity became hypoactive. Finally, 2 of the 3 patients with initial normal platelets became hypoactive while 1 remained normal. There was a significant decrease in ristocetin-induced platelet aggregation after therapy (p0.05. Conclusion: These findings indicate that a significant proportion of chronic myeloid leukemia patients have different patterns of platelet function abnormalities and imatinib mesylate has no effect on these abnormalities, with a significant impairment in ristocetin-induced platelet aggregation.

  5. Effect of ethanol on thrombin-induced platelet phospholipid breakdown and release of [3H]-5-hydroxytryptamine

    International Nuclear Information System (INIS)

    Ethanol has been reported previously to inhibit chemically-induced platelet aggregation and the release of platelet contents. In platelet suspensions the mechanical stimulus of stirring can induce slow aggregation and the loss of endogenous arachidonic acid from phospholipids by activation of platelet phospholipases. These changes are prevented by the presence of ethanol 20-100 mM, whereas, in unstirred suspensions, ethanol alone has no effect on platelet phospholipids. Under similar conditions of reduced platelet: platelet contact, chemical stimuli, such as thrombi, although unable to produce visible aggregation, still cause the release of [3H]-5-hydroxytryptamine from platelets and also initiate the breakdown of platelet phospholipids. Ethanol does not now inhibit the thrombin-induced release of platelet contents and has little effect on phosphatidylinositol breakdown, though it inhibits phosphatidylcholine breakdown. Ethanol may therefore inhibit platelet aggregation by reducing the effect of mechanical and chemical stimuli on the activation of phospholipase A2. In contrast ethanol has rather little effect on the receptor-mediated breakdown of phosphatidylinositol which is apparently sufficient to trigger the release of platelet contents

  6. 新型三唑并[4,5-d]嘧啶类化合物的合成及其抗血小板聚集活性%Synthesis and Anti-platelet Aggregation Activities of Novel Triazolo[ 4,5-d] pyrimidin Compounds

    Institute of Scientific and Technical Information of China (English)

    王兵; 杨静; 姜希明; 刘颖; 刘登科; 王平保

    2016-01-01

    The aminopyrimidines(2) were obtained via the substitution reaction of 4,6-dichloro-2-(pro-pylthio)pyrimidin-5-amine with primary amines.Diazotization and coupling reaction of 2 provided thia-zoles(3).Twenty-six novel triazolo[4,5-d]pyrimidin compounds(6a~6z) were synthesized by the nu-cleophilic subsititution reaction of 3 with substituted amines and hydrolysis orderly.The structures were characterized by 1 H NMR and ESI-MS.The anti-platelet aggregation activities were evaluated by platelet aggregation inhibition tests in rats.The results showed that 6a~6z exhibited certain anti-platelet aggre-gation activities.The inhibition rates of 6d, 6i and 6l were 61.9%, 69.3%and 71.2%, respectively.%以2-丙硫基-4,6-二氯-5-氨基嘧啶为原料,与伯胺类化合物(1)经取代反应制得氨基嘧啶类化合物(2);2经重氮化反应制得三氮唑类化合物(3);3与胺类化合物经亲核取代反应和水解反应合成了26个新型的三唑并[4,5-d]嘧啶类化合物(6a~6z),其结构经1 H NMR和ESI-MS表征。大鼠体内抗血小板聚集模型测试结果表明:26个化合物均具有一定的抗血小板聚集活性,其中,6d,6i和6l的抗血小板聚集活性较强,抑制率分别为61.9%,69.3%和71.2%。

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

    Science.gov (United States)

    Goddard, Amelia; Leisewitz, Andrew L; Kristensen, Annemarie T; Schoeman, Johan P

    2015-09-01

    Using flow cytometry, platelet-leukocyte aggregate (PLA) formation has previously been documented in dogs with a variety of systemic inflammatory disorders and immune-mediated haemolytic anaemia. Platelet activation and subsequent interaction between platelets and leukocytes are important for regulating innate immunity and systemic inflammation. The objective of this study was to investigate PLA formation in canine babesiosis and to determine whether it was associated with outcome. Blood was collected from 36 client-owned dogs diagnosed with Babesia rossi infection and 15 healthy controls using EDTA as anticoagulant. Activated platelets and PLA formation were detected by measuring surface expression of P-selectin (CD62P) on platelets, monocytes and neutrophils. Of the Babesia-infected dogs, 29 survived and seven died. The percentage of CD62P-positive monocytes was significantly higher (P = 0.036) in the Babesia-infected dogs (54%) than in healthy control dogs (35.3%). However, there were no significant differences between the Babesia-infected and control groups for CD62P-positive platelets (4.9% and 1.2%, respectively) and CD62P-positive neutrophils (28.3% and 17.9%, respectively). The percentage of CD62P-positive monocytes was significantly higher (P = 0.019) in the survivors (58.9%) than in healthy control dogs; however, there were no significant differences between the non-survivors (39.2%) and the controls or between survivors and non-survivors. There were no significant differences between groups for the percentage of CD62P-positive platelets (survivors 4.8%; non-survivors 5.3%; controls 1.2%) or CD62P-positive neutrophils (survivors 31.6%; non-survivors 5.6%; controls 17.9%). In conclusion, Babesia-infected dogs, specifically dogs that survived, had a significantly increased percentage of platelet-monocyte aggregates compared to healthy control dogs. PMID:26088270

  8. Cardiac and vascular imaging with labeled platelets and leukocytes

    International Nuclear Information System (INIS)

    The contribution of platelets in atherosclerosis and thrombosis in animal models and in clinical studies has been quantified with 111In-platelet scintigraphy. New in vitro quantitative techniques have been developed using 111In-labeled platelets to determine the number of adherent platelets on deendothelialized surfaces of damaged vessel walls and synthetic vascular grafts. In vivo imaging techniques are semi-quantitative in nature; in these studies 111In radioactivity on thrombotic vessels or graft surfaces of iliac, femoral, or popliteal arteries is compared with contralateral vessels. Background 111In radioactivity in the circulating blood pool of venous and capillary networks and radioactivity in marrow decreases the sensitivity of these techniques. Subtraction of blood pool radioactivity with 99mTc-labeled autologous red cells and calculation of 111In radioactivity associated with platelet thrombus on vessel walls also have been performed for coronary, carotid, and femoral arteries. Although platelet concentrates are used frequently after open heart surgery (one to six per patient), consumption of platelets in the artificial lung or oxygenator, lysis of platelets during pumping, and suction of blood only recently have been quantified with the use of 111In-labeled platelets. These studies also demonstrated far less trauma to platelets with the use of a membrane rather than a bubble oxygenator. Further reduction in platelet consumption and trauma was observed with the use of prostacyclin, a short-acting drug with significant beneficial effect on platelet thrombus reduction and disaggregation of aggregated platelets. The role of polymorphonuclear leukocytes in inflammation, infection and myocardial infarction, and in vivo evaluation with 111In-leukocyte scintigraphy in animals and humans has been described

  9. Platelet turnover in stable coronary artery disease - influence of thrombopoietin and low-grade inflammation.

    Directory of Open Access Journals (Sweden)

    Sanne Bøjet Larsen

    Full Text Available BACKGROUND: Newly formed platelets are associated with increased aggregation and adverse outcomes in patients with coronary artery disease (CAD. The mechanisms involved in the regulation of platelet turnover in patients with CAD are largely unknown. AIM: To investigate associations between platelet turnover parameters, thrombopoietin and markers of low-grade inflammation in patients with stable CAD. Furthermore, to explore the relationship between platelet turnover parameters and type 2 diabetes, prior myocardial infarction, smoking, age, gender and renal insufficiency. METHODS: We studied 581 stable CAD patients. Platelet turnover parameters (immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell-ratio were determined using automated flow cytometry (Sysmex XE-2100. Furthermore, we measured thrombopoietin and evaluated low-grade inflammation by measurement of high-sensitive CRP and interleukin-6. RESULTS: We found strong associations between the immature platelet fraction, immature platelet count, mean platelet volume, platelet distribution width and platelet large cell ratio (r = 0.61-0.99, p<0.0001. Thrombopoietin levels were inversely related to all of the platelet turnover parameters (r = -0.17--0.25, p<0.0001. Moreover, thrombopoietin levels were significantly increased in patients with diabetes (p = 0.03 and in smokers (p = 0.003. Low-grade inflammation evaluated by high-sensitive CRP correlated significantly, yet weakly, with immature platelet count (r = 0.10, p = 0.03 and thrombopoietin (r = 0.16, p<0.001. Also interleukin-6 correlated with thrombopoietin (r = 0.10, p = 0.02. CONCLUSION: In stable CAD patients, thrombopoietin was inversely associated with platelet turnover parameters. Furthermore, thrombopoietin levels were increased in patients with diabetes and in smokers. However, low-grade inflammation did not seem to have a

  10. Erythrocyte aggregation in flowing blood

    International Nuclear Information System (INIS)

    This paper addresses the issue of whether nonionic contrast media (CM) promote thrombosis by the formation of large, irregular red blood cell aggregates with videomicroscopy and a flow chamber, red blood cell aggregates adjacent to an endothelial cell monolayer were imaged at 17 sec-1 in dilute suspensions (hematocrit, --8) at 370C in plasma with 20% CM by non-red blood cell volume. All aggregates were rouleaux (<100 μm) readily dispersed at higher shear rates. Aggregate length in eight experiments was increased 11% by ioxaglate (320 mg of iodine per milliliter), decreased 58% by diatrizoate (370 mg of iodine per milliliter) but reduced similarly (16%) by iohexol (350 mg of iodine per milliliter) and saline. Iohexol did not enhance platelet aggregation on injured monolayers

  11. Platelets in Lung Biology

    Science.gov (United States)

    Weyrich, Andrew S.; Zimmerman, Guy A.

    2013-01-01

    Platelets and the lungs have an intimate relationship. Platelets are anucleate mammalian blood cells that continuously circulate through pulmonary vessels and that have major effector activities in hemostasis and inflammation. The lungs are reservoirs for megakaryocytes, the requisite precursor cell in thrombopoiesis, which is the intricate process by which platelets are generated. Platelets contribute to basal barrier integrity of the alveolar capillaries, which selectively restricts the transfer of water, proteins, and red blood cells out of the vessels. Platelets also contribute to pulmonary vascular repair. Although platelets bolster hemostatic and inflammatory defense of the healthy lung, experimental evidence and clinical evidence indicate that these blood cells are effectors of injury in a variety of pulmonary disorders and syndromes. Newly discovered biological capacities of platelets are being explored in the context of lung defense, disease, and remodeling. PMID:23043249

  12. Multiple signaling pathways mediated by dopamine and calcium ionophore A23187 in human platelets

    International Nuclear Information System (INIS)

    This study was undertaken to investigate the mechanism(s) of platelet aggregation induced by the synergistic action of dopamine (DA) and a Ca/sup +2/-ionophore, A23187. DA showed non significant effect on platelet aggregation over a wide range of concentrations (up to 500 micro M), but did potentiate the aggregation response of A23187. Aggregation induced by A23187 was inhibited by calcium channel blockers (diltiazem and verpamil), receptor blockers (chlorpromazine and haloperidol) and a cyclo-oxygenase inhibitor (indomethacin). However, the inhibitory effect of these blockers was more pronounced (with a selectivity ratio of 1.5-28) in the aggregation induced by synergistic effect of A23187 and DA. A phosphatidylinositol 3-kinase (P1 3-Kinase) inhibitor, wortmanin (1C/sub 50/. 25-30 nM), inhibited aggregation induced by either A23187 or DA and act synergistically. This synergistic effect on platelet aggregation is mediated through multiple signaling pathways. (author)

  13. gamma. -hexachlorocyclohexane (. gamma. -HCH) activates washed rabbit platelets

    Energy Technology Data Exchange (ETDEWEB)

    Lalau-Keraly, C.; Delautier, D.; Benveniste, J.; Puiseux-Dao, S.

    1986-03-01

    In guinea-pig macrophages, ..gamma..-HCH triggers activation of the phosphatidylinositol cycle and Ca/sup 2 +/ mobilization. Since these two biochemical events are also involved in platelet activation, the authors examined the effects of ..gamma..-HCH on washed rabbit platelets. Release of /sup 14/C-serotonin (/sup 14/C-5HT) and ATP from platelets prelabelled with /sup 14/C-5HT was measured simultaneously with aggregation. ..gamma..-HCH induced shape-change, aggregation and release reaction of platelets. Maximal aggregation (89 arbitrary units, AU), was observed using 170 ..mu..M ..gamma..-HCH, and was associated with 38.1 +/- 6.9% and 161 +/- 48 nM for /sup 14/C-5HT and ATP release respectively (mean +/- 1 SD, n=3). Using 80 ..mu..M ..gamma..-HCH yielded 18 AU, 12.8 +/- 1.0% and 27 +/- 14 nM for aggregation, C-5HT and ATP release respectively (n=3). No effect was observed with 40 ..mu.. M ..gamma..-HCH. Aspirin (ASA), a cyclooxygenase blocker, did not affect ..gamma..-HCH-induced platelet activation. Apyrase (APY), an ADP scavenger, inhibited by 90% aggregation induced by 170 ..mu..M ..gamma..-HCH and slightly inhibited (15%) the /sup 14/C-5HT release. In the presence of both ASA and APY, 96% inhibition of aggregation and 48% inhibition of /sup 14/C-5HT release were observed. Thus, ..gamma..-HCH induced platelet activation in a dose-dependent manner ADP, but not cyclooxygenase-dependent arachidonate metabolites, is involved in ..gamma..-HCH-induced aggregation, whereas, both appear to play a role in ..gamma..-HCH-induced release reaction.

  14. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy

    DEFF Research Database (Denmark)

    Poulsen, Tina Svenstrup; Mickley, Hans; Korsholm, Lars;

    2007-01-01

    INTRODUCTION: The aim of the study was to evaluate the test characteristics of the Platelet Function Analyzer-100 (PFA-100) in patients treated with aspirin. METHODS AND RESULTS: The study consisted of two sub-studies. In study 1, 10 patients with ischemic heart disease (IHD) and 10 controls had...... platelet function assessed by optical platelet aggregation and the PFA-100 method in two 5-week periods. Patients with IHD were treated with aspirin 150 mg/day (first 5-week period), and 300 mg/day (second 5-week period), whereas the controls only received aspirin (150 mg/day) during the second 5-week...... period. From the results of study 1, we found that a cut-off value for the PFA-100 collagen/epinephrine cartridge <165 s identified patients not taking aspirin (sensitivity 0.91, specificity 1.00). A good agreement between the PFA-100 method and optical platelet aggregation was found. Within...

  15. 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. PMID:24396535

  16. Evaluation of a BED-SIDE platelet function assay: performance and clinical utility.

    Science.gov (United States)

    Lau, Wei C; Walker, C Ty; Obilby, David; Wash, Mark M; Carville, David G M; Guyer, Kirk E; Bates, Eric R

    2002-01-01

    Platelets have a pivotal role in the initial defense against insult to the vasculature and are also recognized of critical importance in the acute care settings of percutaneous coronary intervention and cardiopulmonary bypass. In these environments both platelet count and function may be markedly compromised. Unfortunately, current assays to evaluate the parameters of platelet count and function are of limited utility for bed-side testing. Moreover, it is suggested that there may be significant inter patient variation in response to antiplatelet therapy that may be exacerbated by other agents (e.g. heparin) that are routinely administered during cardiac intervention. Here we describe a practical, rapid and user-friendly whole blood platelet function assay that has been developed for use in bed-side settings. Platelet agonists were formulated with an anticoagulant and lyophilized in blood collection tubes standardised to receive a l mL fresh whole blood sample. In the presence of an agonist, platelets are activated and interact (aggregate). Using traditional cell counting principles, non-aggregated platelets are counted whereas aggregated platelets are not. The percentage (%) of functional platelets in reference to a baseline tube may then be determined. Results are available within four minutes. Platelet aggregation in whole blood demonstrated good correlation with turbidometric aggregometry for both ADP (r=0.91) and collagen (r=0.88). Moreover, in clinical settings where antiplatelet agents were administered, this rapid, bed-side, platelet function assay demonstrated utility in monitoring patient response to these therapies. This novel bed-side assay of platelet function is extremely suitable for the clinical environment with a rapid turn-around time. In addition, it provides a full haematology profile, including platelet count, and should permit enhancement of transfusion and interventional decisions. PMID:17890800

  17. Platelet inhibition with Ticlopidine in atherosclerotic intermittent claudication.

    OpenAIRE

    Aukland, A; Hurlow, R. A.; George, A J; Stuart, J

    1982-01-01

    Fifty-one men with atherosclerotic intermittent claudication and haemorheological abnormalities completed a double-blind, one-year randomised trial of Ticlopidine (500 mg/day), a new antiplatelet agent. Ticlopidine caused significant inhibition of platelet aggregation but did not fully correct abnormalities of coagulation, viscosity, and fibrinolysis. There was no significant improvement in walking ability, Doppler ankle-pressure indices, or calf blood flow. Sustained platelet inhibition for ...

  18. Thromboembolism in inflammatory bowel disease: role of platelets.

    OpenAIRE

    Webberley, M. J.; M. 't Hart; Melikian, V.

    1993-01-01

    Patients with inflammatory bowel disease are susceptible to thromboembolism and recently small vessel thrombosis has been implicated as an aetiological factor in Crohn's disease. This study therefore investigated platelet function in 104 patients with inflammatory bowel disease of whom eight had previous thromboembolism. Thirty five patients had reproducible spontaneous platelet aggregation of more than 30% (0 in controls) (p < 0.0001). A further 20 patients showed hypersensitivity of platele...

  19. Loss of fibrinogen receptors from the platelet surface during simulated extracorporeal circulation

    International Nuclear Information System (INIS)

    In vitro recirculation of fresh human heparinized blood in an extracorporeal circuit with a membrane oxygenator decreased fibrinogen- induced platelet aggregation and diminished the number of fibrinogen receptors and glycoprotein IIb/IIIa (GPIIb/GPIIIa) antigenic sites on the platelet surface. In seven experiments, the mean +/- SD Km value for fibrinogen (i.e., molar concentration of fibrinogen required to cause 50% of the maximal rate of aggregation) was 1.58 x 10(-7) mol/L +/- 0.68 x 10(-7) mol/L. After recirculation, this value increased to 3.8 x 10(-7) mol/L +/- 1.94 x 10(-7) mol/L. The maximal aggregation rate of chymotrypsin-treated platelets decreased by 40% after 2 hours of recirculation. The number of fibrinogen receptors on platelets, which were treated with chymotrypsin after a recirculation, decreased from 41,370 +/- 24,000 to 13,230 +/- 10,230/platelet under the same conditions. The number of antigenic sites for monoclonal antibody reacting with GPIIb/GPIIIa complex of adenosine diphosphate-stimulated platelets decreased from 34,200 +/- 5,940 to 19,500 +/- 9,680/platelet after recirculation. Prostaglandin E1 (0. 3 mumol/L) in the perfusion circuit preserved the ability of platelets to react with fibrinogen. In conclusion, the loss of fibrinogen receptors from the surface of platelet membranes results from the interaction of platelets with the surfaces of perfusion circuits

  20. The nature of interactions between tissue-type plasminogen activator and platelets

    International Nuclear Information System (INIS)

    To elucidate interactions responsible for inhibition of aggregation of platelets in platelet-rich plasma (PRP) harvested from whole blood preincubated with t-PA, experiments were performed with PRP and washed platelets under diverse conditions of preincubation. Both ADP and collagen induced aggregation were inhibited in PRP unless aprotinin had been added to the preincubated whole blood concomitantly with t-PA. However, in washed platelets prepared after the same exposure aggregation was intact. When washed platelets were supplemented with fibrinogen degradation products (FDPs) in concentrations simulating those in whole blood preincubated with t-PA, aggregation induced with either ADP or collagen was inhibited. Thus, the inhibition in PRP depended on generation of FDPs by activated plasminogen. The functional integrity of surface glycoprotein (GP) IIb/IIIa receptors in washed platelets was documented by autoradiography after SDS-PAGE of surface labeled GPs and by fibrinogen binding despite preincubation of the whole blood or washed platelets themselves with t-PA and plasminogen as long as exogenous calcium (greater than or equal to 0.1 microM) was present. In contrast, when calcium was absent, the platelet GP IIb/IIIa receptor was rendered susceptible to degradation by plasmin, and aggregation was inhibited by preincubation at 37 degrees C even if aprotinin was present when aggregation was being assayed. These observations reconcile disparate results in the literature from studies in vivo and in vitro by demonstrating that inhibition of aggregation of platelets in PRP and in whole blood reflects indirect effects of plasminogen activation rather than direct effects of t-PA or plasmin on the platelets themselves

  1. JUDGMENT AGGREGATION AND PREFERENCE AGGREGATION

    OpenAIRE

    Joanna Ochremiak

    2011-01-01

    In the paper we present an introduction to the theory of judgment aggregation and discuss its relation to the theory of preference aggregation. We compare the formal model of judgment aggregation, based on logic, with the formal model of preference aggregation. Finally, we present a theorem in judgmentaggregation which is an exact analogue of Arrow's theorem for strict preferences.

  2. Reduced serum inhibition of platelet-activating factor activity in preeclampsia.

    Science.gov (United States)

    Benedetto, C; Massobrio, M; Bertini, E; Abbondanza, M; Enrieu, N; Tetta, C

    1989-01-01

    We determined in normal nonpregnant (group 1) women, normal pregnant (group 2) women, and patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity, the presence of detectable amounts of platelet-activating factor in the blood, and platelet responsiveness in vitro to platelet-activating factor, and to other agonists (adenosine diphosphate, collagen, and ristocetin), and prostacyclin (prostaglandin I2). In patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity was significantly lower than that in groups 1 and 2. However, no detectable amounts of platelet-activating factor were observed. The mean values of platelet aggregation induced by platelet-activating factor, adenosine diphosphate, collagen and ristocetin, and the prostaglandin I2-inhibitory concentration of 50% which is inversely correlated with platelet sensitivity to prostaglandin I2, were not significantly different between groups 2 and 3. It is suggested that in preeclampsia the defect in serum inhibitory potential of platelet-activating factor--induced platelet aggregation may contribute to the disturbance in the homeostatic balance between proaggregant and antiaggregant substances. PMID:2912073

  3. Studies on the Biological Effects of Ozone: 10. Release of Factors from Ozonated Human Platelets

    Directory of Open Access Journals (Sweden)

    G. Valacchi

    1999-01-01

    Full Text Available In a previous work we have shown that heparin, in the presence of ozone (O3, promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF, transforming growth factor β1 (TGF-β1 and interleukin-8(IL-8 are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limbischemia treated with O3 autohaemoteraphy (O3-AHT.

  4. Platelet function in stored heparinised autologous blood is not superior to in patient platelet function during routine cardiopulmonary bypass.

    Directory of Open Access Journals (Sweden)

    Rolf C G Gallandat Huet

    Full Text Available BACKGROUND: In cardiac surgery, cardiopulmonary bypass (CPB and unfractionated heparin have negative effects on blood platelet function. In acute normovolemic haemodilution autologous unfractionated heparinised blood is stored ex-vivo and retransfused at the end of the procedure to reduce (allogeneic transfusion requirements. In this observational study we assessed whether platelet function is better preserved in ex vivo stored autologous blood compared to platelet function in the patient during CPB. METHODOLOGY/PRINCIPAL FINDING: We measured platelet aggregation responses pre-CPB, 5 min after the start of CPB, at the end of CPB, and after unfractionated heparin reversal, using multiple electrode aggregometry (Multiplate® with adenosine diphosphate (ADP, thrombin receptor activating peptide (TRAP and ristocetin activated test cells. We compared blood samples taken from the patient with samples taken from 100 ml ex-vivo stored blood, which we took to mimick blood storage during normovolemic haemodilution. Platelet function declined both in ex-vivo stored blood as well as in blood taken from the patient. At the end of CPB there were no differences in platelet aggregation responses between samples from the ex vivo stored blood and the patient. CONCLUSION/SIGNIFICANCE: Ex vivo preservation of autologous blood in unfractionated heparin does not seem to be profitable to preserve platelet function.

  5. Anti-platelet and anti-thrombogenic effects of shikimic acid in sedentary population.

    Science.gov (United States)

    Veach, Daniel; Hosking, Holly; Thompson, Kiara; Santhakumar, Abishek Bommannan

    2016-08-10

    This ex vivo study was performed to evaluate the anti-platelet and anti-thrombogenic potential of shikimic acid (SA), a plant phenolic metabolite. Fasting blood samples were collected from 22 sedentary participants to analyse the effect of varying concentrations of SA (0.1 mM, 0.2 mM, 0.5 mM, 1 mM and 2 mM) on platelet surface-marker expression, platelet aggregation and biomarkers of thrombogenesis. Monocyte-platelet aggregates (CD14/CD42b) and platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31), effective indicators of thrombus formation were evaluated. Procaspase-activating compound 1 (PAC-1) and P-selectin or CD62P were used to assess platelet activation-related thrombogenesis. Adenosine diphosphate (ADP) was used to stimulate the P2Y1/P2Y12 pathway of platelet activation to mimic the in vivo thrombogenic pathway. Platelet aggregation studies utilised both ADP and collagen as exogenous platelet agonists to target both P2Y1/P2Y12 and GPVI pathways of thrombus formation. It was observed with flow cytometry that SA produced a significant antiplatelet effect on PAC-1 (p = 0.03 at 2 mM) and CD62P (p = 0.017, p = 0.036 at 1 mM and 2 mM respectively) expression in addition to lowering monocyte-platelet aggregate formation (p = 0.013, p food intake, could play an important role in reducing platelet activation, aggregation related thrombus formation and biomarkers of thrombogenesis in sedentary individuals. PMID:27480079

  6. Platelets enhance neutrophil transendothelial migration

    Science.gov (United States)

    Platelets are increasingly recognized as important mediators of inflammation in addition to thrombosis. While platelets have been shown to promote neutrophil (PMN) adhesion to endothelium in various inflammatory models, it is unclear whether platelets enhance neutrophil transmigration across inflame...

  7. In vitro screening of Amazonian plants for hemolytic activity and inhibition of platelet aggregation in human blood Testes in vitro de plantas Amazônicas para atividade hemolítica e inibição da agregação plaquetária em sangue humano

    Directory of Open Access Journals (Sweden)

    Viviana Maria Araújo de Oliveira

    2009-01-01

    Full Text Available In the present study, different aerial parts from twelve Amazonian plant species found in the National Institute for Amazon Research's (INPA's Adolpho Ducke Forest Reserve (in Manaus, Amazonas, Brazil were collected. Separate portions of dried, ground plant materials were extracted with water (by infusion, methanol and chloroform (by continuous liquid-solid extraction and solvents were removed first by rotary evaporation, and finally by freeze-drying which yielded a total of seventy-one freeze-dried extracts for evaluation. These extracts were evaluated initially at concentrations of 500 and 100 µg/mL for in vitro hemolytic activity and in vitro inhibition of platelet aggregation in human blood, respectively. Sixteen extracts (23 % of all extracts tested, 42 % of all plant species, representing the following plants: Chaunochiton kappleri (Olacaceae, Diclinanona calycina (Annonaceae, Paypayrola grandiflora (Violaceae, Pleurisanthes parviflora (Icacinaceae, Sarcaulus brasiliensis (Sapotaceae, exhibited significant inhibitory activity towards human platelet aggregation. A group of extracts with antiplatelet aggregation activity having no in vitro hemolytic activity has therefore been identified. Three extracts (4 %, all derived from Elaeoluma nuda (Sapotaceae, exhibited hemolytic activity. None of the plant species in this study has known use in traditional medicine. So, these data serve as a baseline or minimum of antiplatelet and hemolytic activities (and potential usefulness of non-medicinal plants from the Amazon forest. Finally, in general, these are the first data on hemolytic and inhibitory activity on platelet aggregation for the genera which these plant species represent.No presente estudo, partes aéreas obtidas de doze (12 espécies vegetais da Amazônia encontradas na Reserva Florestal Adolpho Ducke (localizada na cidade de Manaus, Estado do Amazonas, Brasil do Instituto Nacional de Pesquisas da Amazônia foram coletadas, secadas e mo

  8. Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation

    Directory of Open Access Journals (Sweden)

    Hou Ssu-Yu

    2010-06-01

    Full Text Available Abstract Background 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA reductase inhibitors (statins have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved. Methods The aim of this study was to systematically examine the detailed mechanisms of simvastatin in preventing platelet activation. Platelet aggregation, flow cytometric analysis, immunoblotting, and electron spin resonance studies were used to assess the antiplatelet activity of simvastatin. Results Simvastatin (20-50 μM exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin. Simvastatin inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i mobilization, thromboxane A2 (TxA2 formation, and phospholipase C (PLCγ2, protein kinase C (PKC, and mitogen-activated protein kinases (i.e., p38 MAPK, JNKs phosphorylation in washed platelets. Simvastatin obviously increased both cyclic AMP and cyclic GMP levels. Simvastatin markedly increased NO release, vasodilator-stimulated phosphoprotein (VASP phosphorylation, and endothelial nitric oxide synthase (eNOS expression. SQ22536, an inhibitor of adenylate cyclase, markedly reversed the simvastatin-mediated inhibitory effects on platelet aggregation, PLCγ2 and p38 MAPK phosphorylation, and simvastatin-mediated stimulatory effects on VASP and eNOS phosphorylation. Conclusion The most important findings of this study demonstrate for the first time that inhibitory effect of simvastatin in platelet activation may involve activation of the cyclic AMP

  9. A Crucial Role of Glycoprotein VI for Platelet Recruitment to the Injured Arterial Wall In Vivo

    OpenAIRE

    Massberg, Steffen; Gawaz, Meinrad; Grüner, Sabine; Schulte, Valerie; Konrad, Ildiko; Zohlnhöfer, Dietlind; Heinzmann, Ulrich; Nieswandt, Bernhard

    2003-01-01

    Platelet adhesion and aggregation at sites of vascular injury is crucial for hemostasis but may lead to arterial occlusion in the setting of atherosclerosis and precipitate diseases such as myocardial infarction. A current hypothesis suggests that platelet glycoprotein (GP) Ib interaction with von Willebrand factor recruits flowing platelets to the injured vessel wall, where subendothelial fibrillar collagens support their firm adhesion and activation. However, so far this hypothesis has not ...

  10. Cell surface thiol isomerases may explain the platelet-selective action of S-nitrosoglutathione

    OpenAIRE

    Xiao, Fang; Gordge, Michael P

    2011-01-01

    S-nitrosoglutathione (GSNO) at low concentration inhibits platelet aggregation without causing vasodilation, suggesting platelet-selective nitric oxide delivery. The mechanism of this selectivity is unknown, but may involve cell surface thiol isomerases, in particular protein disulphide isomerase (csPDI) (EC 5.3.4.1). We have now compared csPDI expression and activity on platelets, endothelial cells and vascular smooth muscle cells, and the dependence on thiol reductase activity of these cell...

  11. Reevaluation of the role of the polar groups of collagen in the platelet-collagen interaction.

    OpenAIRE

    Chesney, C. M.; Pifer, D D; Crofford, L J; Huch, K. M.

    1983-01-01

    Chemical modification of collagen is a tool for exploring the platelet-collagen interaction. Since collagen must polymerize prior to the initiation of platelet aggregation and secretion, modification must be shown to affect platelet-collagen interaction and not collagen-collagen interaction. To address this point, the authors carried out the following chemical modifications on soluble monomeric collagen and preformed fibrillar collagen in parallel: 1) N-and O-acetylation, 2) esterification of...

  12. New 'ex vivo' radioisotopic method of quantitation of platelet deposition

    International Nuclear Information System (INIS)

    We have developed a sensitive and quantitative method of 'ex vivo' evaluation of platelet deposition on collagen strips, from rabbit Achilles tendon, superfused by flowing blood and applied it to four animal species, cat, rabbit, dog and pig. Autologous platelets were labeled with indium-111-tropolone, injected to the animal 24 hr before the superfusion and the number of deposited platelets was quantitated from the tendon gamma-radiation and the blood platelet count. We detected some platelet consumption with superfusion time when blood was reinfused entering the contralateral jugular vein after collagen contact but not if blood was discarded after the contact. Therefore, in order to have a more physiological animal model we decided to discard blood after superfusion of the tendon. In all species except for the cat there was a linear relationship between increase of platelet on the tendon and time of exposure to blood superfusion. The highest number of platelets deposited on the collagen was found in cats, the lowest in dogs. Ultrastructural analysis showed the platelets were deposited as aggregates after only 5 min of superfusion. (orig.)

  13. Anti-platelet therapy in small animal medicine.

    Science.gov (United States)

    Thomason, J; Lunsford, K; Mackin, A

    2016-08-01

    Thromboembolism is a significant complication in many commonly encountered diseases, and can be a devastating sequel to otherwise treatable conditions. Platelets play an essential role in the hemostatic process and, consequently, are associated with thrombus formation. Platelets adhere to denuded vascular subendothelium, recruit additional platelets and cells, aggregate, and provide the catalytic surface for thrombin production and fibrin formation. Therapy to prevent unwanted thrombus formation and thromboembolic crises is essential in the management of hypercoagulable patients. Unfortunately, many of the medications used in veterinary medicine that inhibit or modulate coagulation factors, such as the heparins, are cost prohibitive, only effective when administered by injection or require frequent drug monitoring, and are therefore poor choices for long term at home therapy. While the role of the platelet in pathologic thrombus formation is not fully understood, veterinarians often resort to anti-platelet therapy in the management of patients at risk for thromboembolic complications, because many anti-platelet medications are inexpensive, require minimal drug monitoring, and can be given orally. The aim of this review is to discuss the anti-platelet therapies that are currently being used or being considered for use to inhibit platelet function and reduce thromboembolic complications in hypercoagulable dogs and cats. PMID:26969126

  14. Platelet function in brown bear (Ursus arctos compared to man

    Directory of Open Access Journals (Sweden)

    Särndahl Eva

    2010-06-01

    Full Text Available Abstract Background Information on hemostasis and platelet function in brown bear (Ursus arctos is of importance for understanding the physiological, protective changes during hibernation. Objective The study objective was to document platelet activity values in brown bears shortly after leaving the den and compare them to platelet function in healthy humans. Methods Blood was drawn from immobilized wild brown bears 7-10 days after leaving the den in mid April. Blood samples from healthy human adults before and after clopidogrel and acetylsalicylic acid administration served as control. We analyzed blood samples by standard blood testing and platelet aggregation was quantified after stimulation with various agonists using multiple electrode aggregometry within 3 hours of sampling. Results Blood samples were collected from 6 bears (3 females between 1 and 16 years old and from 10 healthy humans. Results of adenosine diphosphate, aspirin, and thrombin receptor activating peptide tests in bears were all half or less of those in humans. Platelet and white blood cell counts did not differ between species but brown bears had more and smaller red blood cells compared with humans. Conclusion Using three different tests, we conclude that platelet function is lower in brown bears compared to humans. Our findings represent the first descriptive study on platelet function in brown bears and may contribute to explain how bears can endure denning without obvious thrombus building. However, the possibility that our findings reflect test-dependent and not true biological variations in platelet reactivity needs further studies.

  15. Inhibition of rabbit platelet activation in vitro by antagonists of platelet-activating factor (PAF)

    International Nuclear Information System (INIS)

    The authors used washed, [3H]serotonin-labeled rabbit platelets to study the in vitro aggregation and secretion responses induced by graded doses of PAF in the presence or absence of specific antagonists of PAF. These antagonists included CV-3988, L-652,731, triazolam and alprazolam. Platelets were pretreated with either an antagonist or the appropriate diluent for 60 sec prior to the addition of PAF (2 x 10-10 to 2 x 10-7 M). Aggregation was monitored continuously and recorded as the height of the aggregation tracing at 60 sec post-PAF. Secretion of [3H]-serotonin was measured in a sample of the platelets removed at 60 sec post-PAF. When 2 x 10-10 M PAF was used as the stimulus, the concentration of antagonist needed for 50% inhibition (IC50) of secretion was obtained at 0.05 μM, 0.15 μM, 0.6 μM and 2.5 μM, respectively, for L-652,731, CV-3988, triazolam and alprazolam. The corresponding IC50 for aggregation was obtained at 0.2 μM, 0.1 μM, 1.5 μM and 6.5 μM, respectively. The inhibitory effects of these antagonists could be overcome by increasing the dose of PAF used. Although all of the antagonists were capable of completely inhibiting platelet aggregation and secretion, L-652,731 was the most potent PAF antagonist on a molar basis

  16. Clopidogrel discontinuation and platelet reactivity following coronary stenting

    LENUS (Irish Health Repository)

    2011-01-01

    Summary. Aims: Antiplatelet therapy with aspirin and clopidogrel is recommended for 1 year after drug-eluting stent (DES) implantation or myocardial infarction. However, the discontinuation of antiplatelet therapy has become an important issue as recent studies have suggested a clustering of ischemic events within 90 days of clopidogrel withdrawal. The objective of this investigation was to explore the hypothesis that there is a transient ‘rebound’ increase in platelet reactivity within 3 months of clopidogrel discontinuation. Methods and Results: In this prospective study, platelet function was assessed in patients taking aspirin and clopidogrel for at least 1 year following DES implantation. Platelet aggregation was measured using a modification of light transmission aggregometry in response to multiple concentrations of adenosine diphosphate (ADP), epinephrine, arachidonic acid, thrombin receptor activating peptide and collagen. Clopidogrel was stopped and platelet function was reassessed 1 week, 1 month and 3 months later. Thirty-two patients on dual antiplatelet therapy were recruited. Discontinuation of clopidogrel increased platelet aggregation to all agonists, except arachidonic acid. Platelet aggregation in response to ADP (2.5, 5, 10, and 20 μm) and epinephrine (5 and 20 μm) was significantly increased at 1 month compared with 3 months following clopidogrel withdrawal. Thus, a transient period of increased platelet reactivity to both ADP and epinephrine was observed 1 month after clopidogrel discontinuation. Conclusions: This study demonstrates a transient increase in platelet reactivity 1 month after clopidogrel withdrawal. This phenomenon may, in part, explain the known clustering of thrombotic events observed after clopidogrel discontinuation. This observation requires confirmation in larger populations.

  17. Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model

    International Nuclear Information System (INIS)

    Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis. In a new ex vivo whole artery angioplasty model, the authors examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 ± 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 ± 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin. At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation

  18. The influence of platelets, plasma and red blood cells on functional haemostatic assays

    DEFF Research Database (Denmark)

    Bochsen, Louise; Johansson, Pär I.; Kristensen, Annemarie Thuri; Daugaard, Gedske; Ostrowski, Sisse Rye

    2011-01-01

    , removing plasma from platelet concentrates eliminated the TEG response and diminished the Multiplate aggregation response, but readding plasma to the pure platelet concentrates restored the response. Each of the elements in whole blood, plasma, platelets and RBC, affected the Multiplate and TEG results......Functional whole blood haemostatic assays are used increasingly to guide transfusion therapy and monitor medical treatment and are also applied for in-vitro evaluations of the haemostatic potential of stored platelets. We investigated how the cellular and plasmatic elements, both isolated and...... combined, influenced the two methodologically different assays, thrombelastography (TEG) and impedance aggregometry (Multiplate). Platelet-rich plasma (200 × 10/l) or pure plasma (0 platelets), with and without added red blood cells (RBCs), hematocrit 0, 0.15 or 0.29, were produced in vitro from platelet...

  19. Effects of condensation products of biogenic amines on human platelet function

    International Nuclear Information System (INIS)

    Condensation products (CP) are formed by the reaction of biogenic amines with aldehydes and alpha-keto acids. The purpose of this investigation was to examine the effects of CP on platelet function in vitro. The effect of CP on platelet aggregation was examined. Epinephrine-induced aggregation was inhibited, suggesting CP antagonistic activity on the platelet alpha2-adrenergic receptors. Adenosine-diphosphate (ADP), collagen and arachidonic acid induced aggregation was inhibited only at high concentrations. Inhibition of epinephrine and ADP aggregation was reversible, suggesting CP are competitive inhibitors of these agonists. Binding affinities for the platelet alpha2-adrenergic receptor were determined using [3H]-yohimbine, a specific alpha2-receptor antagonist. The order of potency for CP inhibition of [3H]-yohimbine binding paralleled that determined for inhibition of epinephrine-induced aggregation. Platelet uptake of serotonin (5-HT) was competitively inhibited by CP, with the exception of salsolinol, which appears to be stimulatory. Release of 5-HT from platelets was induced by CP, with betacarbolines being more potent than tetrahydroisoquinolines. Evidence suggests that CP cause release by displacement of 5-HT from intraplatelet storage sites since this effect can be inhibited by imipramine, thus preventing accumulation of CP by platelets

  20. Platelet Function Tests

    Science.gov (United States)

    ... of the clotting process in the body ( in vivo ). A person with normal platelet function test results may still experience excessive bleeding or inappropriate clotting during and after a surgery. Most samples for platelet function testing are only stable for a very short period ...

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

    Directory of Open Access Journals (Sweden)

    Véronique Ollivier

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

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

    Directory of Open Access Journals (Sweden)

    Francisco Javier Tovar-Lopez

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

  3. Platelet functional and transcriptional changes induced by intralipid infusion.

    Science.gov (United States)

    Beaulieu, Lea M; Vitseva, Olga; Tanriverdi, Kahraman; Kucukural, Alper; Mick, Eric; Hamburg, Naomi; Vita, Joseph; Freedman, Jane E

    2016-06-01

    Multiple studies have shown the effects of long-term exposure to high-fat or western diets on the vascular system. There is limited knowledge on the acute effects of high circulating fat levels, specifically on platelets, which have a role in many processes, including thrombosis and inflammation. This study investigated the effects of acute, high-fat exposure on platelet function and transcript profile. Twenty healthy participants were given an intravenous infusion of 20% Intralipid emulsion and heparin over 6 hours. Blood samples were taken prior to and the day after infusion to measure platelet function and transcript expression levels. Platelet aggregation was not significantly affected by Intralipid infusion, but, when mitochondria function was inhibited by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) or oligomycin, platelet aggregation was higher in the post-infusion state compared to baseline. Through RNA sequencing, and verified by RT-qPCR, 902 miRNAs and 617 mRNAs were affected by Intralipid infusion. MicroRNAs increased include miR-4259 and miR-346, while miR-517b and miR-517c are both decreased. Pathway analysis identified two clusters significantly enriched, including cell motility. In conclusion, acute exposure to high fat affects mitochondrial-dependent platelet function, as well as the transcript profile. PMID:26940969

  4. Temporal and pharmacological characterization of angiostatin release and generation by human platelets: implications for endothelial cell migration.

    Directory of Open Access Journals (Sweden)

    Aneta Radziwon-Balicka

    Full Text Available Platelets play an important role in thrombosis and in neo-vascularisation as they release and produce factors that both promote and suppress angiogenesis. Amongst these factors is the angiogenesis inhibitor angiostatin, which is released during thrombus formation. The impact of anti-thrombotic agents and the kinetics of platelet angiostatin release are unknown. Hence, our objectives were to characterize platelet angiostatin release temporally and pharmacologically and to determine how angiostatin release influences endothelial cell migration, an early stage of angiogenesis. We hypothesized anti-platelet agents would suppress angiostatin release but not generation by platelets. Human platelets were aggregated and temporal angiostatin release was compared to vascular endothelial growth factor (VEGF. Immuno-gold electron microscopy and immunofluorescence microscopy identified α-granules as storage organelles of platelet angiostatin. Acetylsalicylic acid, MRS2395, GPIIb/IIIa blocking peptide, and aprotinin were used to characterize platelet angiostatin release and generation. An endothelial cell migration assay was performed under hypoxic conditions to determine the effects of pharmacological platelet and angiostatin inhibition. Compared to VEGF, angiostatin generation and release from α-granules occurred later temporally during platelet aggregation. Consequently, collagen-activated platelet releasates stimulated endothelial cell migration more potently than maximally-aggregated platelets. Platelet inhibitors prostacyclin, S-nitroso-glutathione, acetylsalicylic acid, and GPIIb/IIIa blocking peptide, but not a P2Y12 inhibitor, suppressed angiostatin release but not generation. Suppression of angiostatin generation in the presence of acetylsalicylic acid enhanced platelet-stimulated endothelial migration. Hence, the temporal and pharmacological modulation of platelet angiostatin release may have significant consequences for neo

  5. Anti-aggregatory and fibrinolytic effects of time-released garlic powder tablets

    OpenAIRE

    Alexander Orekhov; Vasily Karagodin; Igor Sobenin

    2012-01-01

    The double-blinded placebo-controlled randomized crossover study was performed in 29 atherosclerotic men (35 to 70 years old) suffering from cerebral atherosclerosis and chronic cerebrovascular insufficiency to elucidate the effect of time-released garlic powder tablets Allicor on platelet aggregation and serum fibrinolytic activity. It has been demonstrated that Allicor 14-days treatment significantly inhibited ADP-induced platelet aggregation by 25.4% (p

  6. Micro-scale dynamic simulation of erythrocyte-platelet interaction in blood flow.

    Science.gov (United States)

    AlMomani, T; Udaykumar, H S; Marshall, J S; Chandran, K B

    2008-06-01

    Platelet activation, adhesion, and aggregation on the blood vessel and implants result in the formation of mural thrombi. Platelet dynamics in blood flow is influenced by the far more numerous erythrocytes (RBCs). This is particularly the case in the smaller blood vessels (arterioles) and in constricted regions of blood flow (such as in valve leakage and hinge regions) where the dimensions of formed elements of blood become comparable with that of the flow geometry. In such regions, models to predict platelet motion, activation, aggregation and adhesion must account for platelet-RBC interactions. This paper studies platelet-RBC interactions in shear flows by performing simulations of micro-scale dynamics using a computational fluid dynamics (CFD) model. A level-set sharp-interface immersed boundary method is employed in the computations in which RBC and platelet boundaries are tracked on a two-dimensional Cartesian grid. The RBCs are assumed to have an elliptical shape and to deform elastically under fluid forces while the platelets are assumed to behave as rigid particles of circular shape. Forces and torques between colliding blood cells are modeled using an extension of the soft-sphere model for elliptical particles. RBCs and platelets are transported under the forces and torques induced by fluid flow and cell-cell and cell-platelet collisions. The simulations show that platelet migration toward the wall is enhanced with increasing hematocrit, in agreement with past experimental observations. This margination is seen to occur due to hydrodynamic forces rather than collisional forces or volumetric exclusion effects. The effect of fluid shear forces on the platelets increases exponentially as a function of hematocrit for the range of parameters covered in this study. The micro-scale analysis can be potentially employed to obtain a deterministic relationship between fluid forces and platelet activation and aggregation in blood flow past cardiovascular implants

  7. Rational Aggregation

    OpenAIRE

    Bruce Chapman

    2002-01-01

    In two recent papers, Christian List and Philip Pettit have argued that there is a problem in the aggregation of reasoned judgements that is akin to the aggregation of the preference problem in social choice theory.1 Indeed, List and Pettit prove a new general impossibility theorem for the aggregation of judgements, and provide a propositional interpretation of the social choice problem that suggests it is a special case of their impossibility result.2 Specifically, they show that no judgemen...

  8. In vitro studies with an anti-platelet monoclonal antibody; P256

    International Nuclear Information System (INIS)

    P256 is a platelet-specific monoclonal antibody. It has potential as a diagnostic agent for use in thrombus detection by radioimmunoscintigraphy. However, the whole antibody has been reported to cause platelet aggregation. The object of the present study was to determine the effects of the F(ab')2 and Fab' fragments of P256 on human platelets in vitro. Gel-filtered platelets were prepared from citrated venous blood, and aggregation was studied at 370C using the method of Born. The whole antibody caused aggregation over the concentration range 10-9-10-7 M, with a maximum of 70% aggregation. The F(ab')2 fragment was less potent with a maximum response of only 45%. The monovalent Fab' fragment caused no aggregation at concentrations up to 10-7 M. However, binding studies with 111In-labelled monovalent Fab' fragment demonstrated saturable displaceable binding. Aggregation induced by the divalent forms of the antibody was partially dependent upon added fibrinogen. It is concluded that the monovalent Fab' fragment of P256 may be used in platelet-labelling studies without risk of inducing aggregation irrespective of concentration. The whole antibody, or its divalent F(ab')2 fragment, may also be used provided their concentrations are kept below 10-9 M. (author)

  9. Platelet alloimmunization after transfusion

    DEFF Research Database (Denmark)

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

    1997-01-01

    (17.9%), of whom 18 (15.4%) had had no detectable antibodies before transfusion. There was a positive correlation between the transfused load of immunogenic materials and the frequency of alloimmunization against HLA antigens. In one third of the immunized patients, there was no history of previous......BACKGROUND AND OBJECTIVES: The frequency of platelet-specific antibodies after one series of blood transfusions has not been reported, and in multiply transfused patients is controversial. MATERIALS AND METHODS: We studied the frequency of alloimmunization against platelet antigens in 117 patients......-antibody-specific immobilization of platelet antigen assay. HLA antibodies were detected by the standard lymphocyte cytotoxicity techniques. RESULTS: We found platelet-specific anti-HPA-5b (anti-Bra) in 2 cases (1.7%). One antibody was the result of de novo immunization. We detected lymphocytotoxic HLA antibodies in 21 patients...

  10. Influence of proton pump inhibitors omeprazole on the platelet aggregation rate of clopidogrel in patients with acute coronary syndrome%奥美拉唑对急性冠脉综合征患者氯吡格雷抗血小板聚集率的影响

    Institute of Scientific and Technical Information of China (English)

    洪芳德; 王邦宁

    2014-01-01

    Objective To explore the influence of proton pump inhibitors (PPI)omeprazole on the platelet aggregation rate of clopidogrel in patients with acute coronary syndrome (ACS).Methods A total of 159 patients with ACS were selected,based on the standardized treatment,the patients were divided into the two groups according to the illness.65 cases in the treatment group were given omeprazole (20mg/d).94 cases in the control group were not given omeprazole.Both two groups were given aspirin(100mg/d) and clopidogrel (75mg/d).The platelet reactivity index(PRI) and clopidogrel active metabolites (clopi-H4)were detected five days later.Results After treatment for 5 days,the number of PRI > 50% in the treatment group and control group was 12 cases(18.5%) and 7 cases (7.4%) (x2 =4.431,P < 0.05).The clopi-H4 levels in the treatment group and control group were 332.8 mmol/L (SD 371.8) and 600.3 mmol/L(SD 885.2) (t =-2.298,P < 0.05).Conclusion In patients with ACS,combined omeprazole and clopidogrel can reduce the concentration of clopidogrel active metabolites clopi-H4,inhibition of clopi dogrel platelet aggregation.%目的 观察奥美拉唑对急性冠脉综合征(ACS)患者氯吡格雷抗血小板聚集率(PRI)的影响.方法 选择ACS患者159例,在给予标准化治疗的基础上,根据病情需要分为两组,其中一组给予奥美拉唑(20 mg/d)治疗(治疗组,65例),另一组未使用(对照组,94例),两组均给予阿司匹林(100 mg/d)和氯吡格雷(75 mg/d)维持治疗,5d后检测两组患者PRI和氯吡格雷活性代谢产物浓度(clopi-H4).结果 治疗5d后,治疗组与对照组中患者PRI> 50%分别为12例(18.5%)和7例(7.4%)(x2=4.431,P<0.05),clopi-H4分别为332.8 mmol/L(标准差SD 371.8)和600.3 mmol/L(标准差SD 885.2)(t=-2.298,P<0.05).结论 ACS患者联合使用奥美拉唑及氯吡格雷,可降低clopi-H4,抑制氯吡格雷抗血小板聚集作用.

  11. Antiplatelet aggregation principles from Ephemerantha lonchophylla.

    Science.gov (United States)

    Chen, C C; Huang, Y L; Teng, C M

    2000-05-01

    Bioactivity-directed separation led to the identification of four compounds, viz. denbinobin (1), 3,7-dihydroxy-2,4-dimethoxyphenanthrene (2), 3-methylgigantol (3), and erianthridin (4) from the ethanolic extract of Ephemerantha lonchophylla. Antiplatelet tests were carried out using 4 different aggregation inducers, viz. arachidonic acid (AA), thrombin, collagen and platelet activating factor (PAF). The results indicated that only compounds 2, 3, and 4 exhibited generally significant anti-aggregation activities with that against AA-induced aggregation being most effective. Estimated IC50, values in this regard for 2, 3, and 4 were 24 microM, 30 microM and 9 microM, respectively. PMID:10865460

  12. Weighted aggregation

    Science.gov (United States)

    Feiveson, A. H. (Principal Investigator)

    1979-01-01

    The use of a weighted aggregation technique to improve the precision of the overall LACIE estimate is considered. The manner in which a weighted aggregation technique is implemented given a set of weights is described. The problem of variance estimation is discussed and the question of how to obtain the weights in an operational environment is addressed.

  13. Radioimmunoassay of platelet proteins

    International Nuclear Information System (INIS)

    The radioimmunoassay of platelet-specific proteins has proven to be an excellent way of monitoring platelet activation in vivo. In contrast to earlier methods such as aggregometry, which has been the major tool used in the evaluation of antiplatelet drugs, the RIAs are capable of working with samples which have been subjected to physiological conditions such as haematocrit, oxygen tension, shear rate and ionized calcium concentration. Also, in contrast to aggregometry, no choice of agonist is necessary. Thus, for the first time it has been possible to monitor the effects of therapeutic intervention with drugs upon the platelet release reaction in vivo. It seems reasonable to equate the release reaction in vivo with activation in vivo, though the stimuli necessarily remain unknown. Nevertheless, the fact that a significant number of the compounds mentioned in Table 3 are indeed capable of reducing platelet activation in vivo and that this effect can be measured objectively is a major step forward in our understanding of platelet pharmacology. Two important goals remain to be achieved, however, the establishment of nonhuman animal models for the evaluation of newer compounds in vivo and longer-term goal of proving in the clinical setting the relevance or otherwise of platelet activation per se to the clinical outcome of a particular disease. In this respect, the availability of accurate, reliable and specific radioimmunoassays has a central role

  14. Effects on platelet function of combination etoposide and carboplatin chemotherapy in pediatric oncology patients.

    Science.gov (United States)

    Pignatelli, P; Properzi, E; Pisani, M; Clerico, A; Schiavetti, A; Lenti, L; Pulcinelli, F M; Ferroni, P; Gazzaniga, P P

    1998-01-01

    The effects of a therapeutic course of the combination of carboplatin and etoposide on platelet function have been evaluated in 10 pediatric patients with brain tumors. Platelet count, in vitro aggregation tests, P-selectin expression and agonist-induced ATP release were evaluated before, and 7 and 15 days after one cycle of chemotherapy. The analysis of the results demonstrated the presence of an in vitro platelet aggregation defect in response to collagen and arachidonic acid in all patients 7 days after therapy. A concomitant decrease of collagen- and arachidonic acid-induced ATP release was also observed. Both platelet aggregation and ATP release returned to baseline values 15 days after chemotherapy administration. Conversely, in vitro platelet aggregation and secretion induced by ADP and epinephrine were unaltered by carboplatin and etoposide administration. Furthermore, P-selectin expression was negative at baseline and did not change after chemotherapy. These results support the hypothesis that combination etoposide and carboplatin chemotherapy in pediatric patients is responsible for possible disturbances in biochemical pathways required for platelet secretion and aggregation. PMID:16793755

  15. Fabricating bio-inspired micro/nano-particles by polydopamine coating and surface interactions with blood platelets

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Wei [Jiangsu Provincial Key Lab for Interventional Medical Devices, Huaiyin Institute of Technology, Huaian 223003 (China); State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Shi, Qiang, E-mail: shiqiang@ciac.ac.cn [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Hou, Jianwen; Gao, Jian; Li, Chunming; Jin, Jing; Shi, Hengchong [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Yin, Jinghua, E-mail: yinjh@ciac.ac.cn [State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)

    2015-10-01

    Graphical abstract: The particles or particle aggregations activate the blood platelets and provide the physical adhesive sites for platelets adhesion. - Highlights: • Particles with varied sizes and surface properties were fabricated by facile polydopamine (PDA) coating on polystyrene microsphere. • The direct interaction between PDA particles and blood platelets was qualitatively investigated. • The knowledge on platelet–particle interactions provided the basic principle to select biocompatible micro/nano-particles in biomedical field. - Abstract: Although bio-inspired polydopamine (PDA) micro/nano-particles show great promise for biomedical applications, the knowledge on the interactions between micro/nano-particles and platelets is still lacking. Here, we fabricate PDA-coated micro/nano-particles and investigate the platelet–particle surface interactions. Our strategy takes the advantage of facile PDA coating on polystyrene (PS) microsphere to fabricate particles with varied sizes and surface properties, and the chemical reactivity of PDA layers to immobilize fibrinogen and bovine serum albumin to manipulate platelet activation and adhesion. We demonstrate that PS particles activate the platelets in the size-dependent manner, but PDA nanoparticles have slight effect on platelet activation; PS particles promote platelet adhesion while PDA particles reduce platelet adhesion on the patterned surface; Particles interact with platelets through activating the glycoprotein integrin receptor of platelets and providing physical sites for initial platelet adhesion. Our work sheds new light on the interaction between platelets and particles, which provides the basic principle to select biocompatible micro/nano-particles in biomedical field.

  16. Fabricating bio-inspired micro/nano-particles by polydopamine coating and surface interactions with blood platelets

    International Nuclear Information System (INIS)

    Graphical abstract: The particles or particle aggregations activate the blood platelets and provide the physical adhesive sites for platelets adhesion. - Highlights: • Particles with varied sizes and surface properties were fabricated by facile polydopamine (PDA) coating on polystyrene microsphere. • The direct interaction between PDA particles and blood platelets was qualitatively investigated. • The knowledge on platelet–particle interactions provided the basic principle to select biocompatible micro/nano-particles in biomedical field. - Abstract: Although bio-inspired polydopamine (PDA) micro/nano-particles show great promise for biomedical applications, the knowledge on the interactions between micro/nano-particles and platelets is still lacking. Here, we fabricate PDA-coated micro/nano-particles and investigate the platelet–particle surface interactions. Our strategy takes the advantage of facile PDA coating on polystyrene (PS) microsphere to fabricate particles with varied sizes and surface properties, and the chemical reactivity of PDA layers to immobilize fibrinogen and bovine serum albumin to manipulate platelet activation and adhesion. We demonstrate that PS particles activate the platelets in the size-dependent manner, but PDA nanoparticles have slight effect on platelet activation; PS particles promote platelet adhesion while PDA particles reduce platelet adhesion on the patterned surface; Particles interact with platelets through activating the glycoprotein integrin receptor of platelets and providing physical sites for initial platelet adhesion. Our work sheds new light on the interaction between platelets and particles, which provides the basic principle to select biocompatible micro/nano-particles in biomedical field

  17. P-Selectin-Mediated Adhesion between Platelets and Tumor Cells Promotes Intestinal Tumorigenesis in Apc(Min/+) Mice.

    Science.gov (United States)

    Qi, Cuiling; Li, Bin; Guo, Simei; Wei, Bo; Shao, Chunkui; Li, Jialin; Yang, Yang; Zhang, Qianqian; Li, Jiangchao; He, Xiaodong; Wang, Lijing; Zhang, Yajie

    2015-01-01

    Studies have indicated that platelets play an important role in tumorigenesis, and an abundance of platelets accumulate in the ovarian tumor microenvironment outside the vasculature. However, whether cancer cells recruit platelets within intestinal tumors and how they signal adherent platelets to enter intestinal tumor tissues remain unknown. Here, we unexpectedly found that large numbers of platelets were deposited within human colorectal tumor specimens using immunohistochemical staining, and these platelets were fully associated with tumor development. We further report the robust adhesion of platelet aggregates to tumor cells within intestinal tumors, which occurs via a mechanism that is dependent on P-selectin (CD62P), a cell adhesion molecule that is abundantly expressed on activated platelets. Using spontaneous intestinal tumor mouse models, we determined that the genetic deletion of P-selectin suppressed intestinal tumor growth, which was rescued by the infusion of wild-type platelets but not P-selectin(-/-) platelets. Mechanistically, platelet adhesion to tumor cells induced the secretion of vascular endothelial growth factor (VEGF) to promote angiogenesis and accelerate intestinal tumor cell proliferation. Our results indicate that the adherence of platelets to tumor cells could promote tumor growth and metastasis. By targeting this platelet-tumor cell interaction, recombinant soluble P-selectin may have therapeutic value for the treatment of intestinal tumors. PMID:25999791

  18. Loss of platelet alpha 2-adrenergic receptors during simulated extracorporeal circulation: prevention with prostaglandin E1

    International Nuclear Information System (INIS)

    Cardiopulmonary bypass prolongs bleeding time and increases postoperative blood loss. During in vitro recirculation in an extracorporeal circuit containing a membrane oxygenator and primed with fresh heparinized human blood, the authors previously observed thrombocytopenia, impaired platelet aggregation, and depletion of granular contents, all of which were prevented with prostaglandin E1 (PGE1). To investigate these changes further, they studied the number and affinity of platelet alpha 2-adrenergic receptors by measuring the binding of 3H-yohimbine. Before recirculation, they found 235 alpha 2-adrenergic receptors per platelet, a Kd of 3.37 nmol/L, complete aggregation with 1.04 mumol/L epinephrine, and a platelet count of 281,000 microliters-1. After 2 minutes of recirculation, 9.44 mumol/L epinephrine was required to produce complete aggregation, and the platelet count was 104,000 microliters-1 (44% of control). After 2 hours of recirculation, the platelet count had increased to 123,000 microliters-1. However, epinephrine did not induce platelet aggregation even at 100 mumol/L. Moreover, alpha 2-adrenergic binding sites were not detectable, and affinity for yohimbine could not be calculated. Two minutes after PGE1 0.3 mumol/L was added to the circuit, platelet numbers, response to epinephrine, alpha 2-adrenergic binding sites per platelet, and affinity for yohimbine were not significantly different from control values. At 2 hours, the number of alpha 2-adrenergic sites was not significantly changed from control, but the affinity of yohimbine for platelets was significantly decreased 2.5-fold

  19. 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; Kaltoft, Anne; Hansen, Hans-Henrik Tilsted; Jensen, Lisette Okkels; Hvas, Anne-Mette; Kristensen, Steen Dalby

    when assessed by multiple electrode aggregometry induced by collagen (pcitrated blood = 0.003; phirudinized blood < 0.0001) and by arachidonic acid (pcitrated blood = 0.16; phirudinized blood = 0.04), respectively. Similarly, platelet aggregation assessed by VerifyNow was higher in ST cases (p = 0...... were treated with aspirin 75 mg once daily. Platelet function was assessed by multiple electrode aggregometry in citrated and hirudinized blood and by VerifyNow Aspirin Assay (Accumetrics, San Diego, California). Flow cytometric determination of the immature platelet fraction was performed to evaluate...... platelet turnover. Platelet activation was evaluated by soluble serum P-selectin. Compliance was confirmed by serum thromboxane B2. Results All patients were fully compliant, which was confirmed by suppressed levels of serum thromboxane B2. Platelet aggregation was increased in patients with previous ST...

  20. Indium Labeled Platelet Deposition Following CO2 Laser Or Surgical Endarterectomy

    Science.gov (United States)

    McVicker, John H.; Day, Arthur L.; Seeger, James M.

    1989-09-01

    Endovascular damage from CO2, Nd:YAG, or argon laser can be considerable, causing reduced vascular biosynthesis of prostacyclin and precipitating platelet aggregation. However, the degree of platelet thrombus formation has not been directly quantified. Using Indium labeled platelets, platelet accumulation after low radiant energy CO2 laser endarterectomy was compared to accumulation after standard microsurgical endarterectomy in normal canine carotid arteries. Undisturbed adjacent segments from the same arteries served as controls. Platelet deposition (Indium activity per minute per milligram arterial tissue) was significantly greater on laser treated segments than on surgical (p=0.002) or control (p=0.002) segments. This confirms prior histologic evidence of increased acute platelet deposition after CO2 laser endarterectomy and suggests the need for further investigation of the thrombogenicity of laser angioplasty.

  1. Platelets in Pulmonary Hypertension: a Causative Role or a Simple Association?

    Directory of Open Access Journals (Sweden)

    Keyhan Sayadpour Zanjani

    2012-06-01

    Full Text Available Pathophysiology of pulmonary arterial hypertension is based on three basic mechanisms: thrombotic pulmonary vascular lesions, vasoconstriction and vascular remodeling. Platelets are related to all of these mechanisms by their aggregation, production, storage and release of several mediators. The role of platelets is more prominent in some types of pulmonary arterial hypertension, including those which are secondary to inflammatory and infectious diseases, hemoglobinopathies, essential thrombocythemia, drugs, thromboembolism, and cardiac surgery. Most pulmonary antihypertensive drugs have a negative effect on platelets. In this review, the mechanisms of platelets association with pulmonary arterial hypertension, those types of pulmonary arterial hypertension with greatest platelet contribution to their pathophysiology, and the effects of pulmonary antihypertensive drugs on platelets are summarized.

  2. Adhesion of human platelets to serum amyloid A.

    Science.gov (United States)

    Urieli-Shoval, Simcha; Shubinsky, George; Linke, Reinhold P; Fridkin, Mati; Tabi, Israel; Matzner, Yaacov

    2002-02-15

    Serum amyloid A (SAA) is an acute phase reactant, and its level in the blood is elevated to 1000-fold in response of the body to trauma, infection, inflammation, and neoplasia. SAA was reported to inhibit platelet aggregation and to induce adhesion of leukocytes. This study looked at adhesion of human platelets to SAA. Immobilized SAA supported the adhesion of human washed platelets; level of adhesion to SAA was comparable to fibronectin and lower than to fibrinogen. Adhesion to SAA was further enhanced by Mn(2+) and the physiological agonist, thrombin. Platelet adhesion to SAA was completely abolished by anti-SAA antibody. SAA-induced adhesion was inhibited by antibodies against the integrin receptor alphaIIbbeta3, by the peptide GRGDSP and by SAA-derived peptide containing YIGSR-like and RGD-like adhesion motifs (amino acids 29 to 42). Adhesion was not inhibited by control immunoglobulin G, by antibody against the integrin receptor alphaVbeta3, by the peptide GRGESP, and by SAA-derived peptide that includes incomplete RGD motif. SAA-derived peptide 29 to 42 also inhibited platelet adhesion to fibronectin. Transfected human melanoma cells expressing alphaIIbbeta3 adhered to SAA, whereas transfected cells expressing alphaVbeta3 did not. By using flow cytometry, the alphaIIbbeta3 cells displayed significantly higher levels of binding of soluble SAA than the alphaVbeta3 cells. These data indicate that human platelets specifically adhere to SAA in an RGD- and alphaIIbbeta3-dependent manner. Thus, SAA may play a role in modulating platelet adhesion at vascular injury sites by sharing platelet receptors with other platelet-adhesive proteins. PMID:11830469

  3. A Study on the radiation effects for the function and structure of rabbit blood platelets in various dose rates

    Energy Technology Data Exchange (ETDEWEB)

    Okumura, Kohichi (Nippon Dental Univ., Tokyo (Japan))

    1991-12-01

    Mature peripheral platelets in rabbits were irradiated with a total 10 Gy of {sup 60}Co-{gamma} rays at the average dose rates of 0.2, 0.5, 1.0, 1.5 and 1.7 Gy/min. The effects was evaluated from the functional aspect by determining the ability of platelets to aggregate and replease, and the metabolic aspect by examining the kinetics of prostaglandin in platelets. In addition, platelet structure was compared using an electron microscope. The ability of platelets to aggregate and release was accelerated in all irradiated groups, compared with a non-irradiated group, especially in groups with average dose rates of 0.5 Gy/min and 1.0 Gy/min. The amount of MDA, a final product of prostaglandin in platelets, increased in all irradiated groups in comparison with the non-irradiated group, especially in the 0.5 Gy/min, 1.0 Gy/min and 1.5 Gy/min groups. Observation with a scanning electron microscope revealed a clear rock-like appearance of the surface of aggregates of platelets and a larger number of pseudopodia with longer projections in the 1.0 Gy/min group than in the non-irradiated group. Moreover, the surfaces of the aggregates in the 1.7 Gy/min group, but the adhension between psudopodia of the platelet aggregates was weaker than that of 1.0 Gy/min group. In observation with a transmission electron microscope, dense bodies that released their contents were noticed in platelet aggregates, and a stenopeic appearance between psudopodia and between platelets, and density aggregated platelets were observed in the 1.0 Gy/min irradiated group. Vacuolation of granules in platelets was more marked in aggregates of 1.7 Gy/min group than in that of the non-irradiated group, and large numbers of platelets with uneven surfaces were observed. Therefore, the effects of dose rates were found to be closely related to changes in structures, as well as to the inner function of platelets. (author).

  4. A Study on the radiation effects for the function and structure of rabbit blood platelets in various dose rates

    International Nuclear Information System (INIS)

    Mature peripheral platelets in rabbits were irradiated with a total 10 Gy of 60Co-γ rays at the average dose rates of 0.2, 0.5, 1.0, 1.5 and 1.7 Gy/min. The effects was evaluated from the functional aspect by determining the ability of platelets to aggregate and replease, and the metabolic aspect by examining the kinetics of prostaglandin in platelets. In addition, platelet structure was compared using an electron microscope. The ability of platelets to aggregate and release was accelerated in all irradiated groups, compared with a non-irradiated group, especially in groups with average dose rates of 0.5 Gy/min and 1.0 Gy/min. The amount of MDA, a final product of prostaglandin in platelets, increased in all irradiated groups in comparison with the non-irradiated group, especially in the 0.5 Gy/min, 1.0 Gy/min and 1.5 Gy/min groups. Observation with a scanning electron microscope revealed a clear rock-like appearance of the surface of aggregates of platelets and a larger number of pseudopodia with longer projections in the 1.0 Gy/min group than in the non-irradiated group. Moreover, the surfaces of the aggregates in the 1.7 Gy/min group, but the adhension between psudopodia of the platelet aggregates was weaker than that of 1.0 Gy/min group. In observation with a transmission electron microscope, dense bodies that released their contents were noticed in platelet aggregates, and a stenopeic appearance between psudopodia and between platelets, and density aggregated platelets were observed in the 1.0 Gy/min irradiated group. Vacuolation of granules in platelets was more marked in aggregates of 1.7 Gy/min group than in that of the non-irradiated group, and large numbers of platelets with uneven surfaces were observed. Therefore, the effects of dose rates were found to be closely related to changes in structures, as well as to the inner function of platelets. (author)

  5. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    JonasSDe Jong

    2010-12-01

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

  6. Effect of taurine on platelets and the plasma coagulation system.

    Science.gov (United States)

    Miglis, Mitchell; Wilder, Donna; Reid, Thomas; Bakaltcheva, Irina

    2002-02-01

    It is not yet clear what exact mechanisms are at work in hibernating animals that prevent clot formation and maintain tissue perfusion under conditions of very slow blood flow and increased blood viscosity brought about by the low temperatures. It has been shown that the total amino acid pool increases more then two fold in hibernating animals with taurine accounting for about 50% of this increase [Storey et al., Proc Natl Acad Sci USA 1988; 85(21): 8350-4]. This work investigates the effect of taurine on platelets and the plasma coagulation system. Taurine was added at different concentrations in the range between 5 and 25 mM to donor plasma. Using STA/STA Compact coagulation analyzer the following tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). At the highest concentration tested (25 mM) taurine prolonged TT by 9%. The prolongation was statistically significant but not clinically significant retaining TT within normal limits (16.7-20.7 s). PT and APTT remained unchanged by taurine. The effect of taurine on platelets was assessed by platelet aggregation by thrombin, extent of platelet shape change (ESC) induced by ADP, and thrombelastography. Taurine at 5 mM final concentration inhibited platelet aggregation by 10%. Increasing taurine concentration to 25 mM did not result in a further augmentation of the inhibitory effect. ESC was unaffected by taurine. Clot strength determined by thrombelastography also remained unchanged by taurine. PMID:11918831

  7. Use of 8-methoxypsoralen and long-wavelength ultraviolet radiation for decontamination of platelet concentrates

    International Nuclear Information System (INIS)

    Transmission of viral diseases through blood products remains an unsolved problem in transfusion medicine. We have developed a psoralen photochemical system for decontamination of platelet concentrates in which platelets are treated with long wavelength ultraviolet radiation (UVA, 320-400 nm) in the presence of 8-methoxypsoralen (8-MOP). Bacteria, RNA viruses, and DNA viruses ranging in genome size from 1.2 x 10(6) daltons, encompassing the size range of human pathogens, were inoculated into platelet concentrates and subjected to treatment. This system inactivated 25 to 30 logs/h of bacteria Escherichia coli or Staphylococcus aureus, 6 logs/h of bacteriophage fd, 0.9 log/h of bacteriophage R17 and 1.1 logs/h of feline leukemia virus (FeLV) in platelet concentrates maintained in standard storage bags. Platelet integrity and in vitro function before, immediately following photochemical treatment, and during prolonged storage after treatment, were evaluated by measuring: (1) extracellular pH; (2) platelet yields; (3) extracellular lactate dehydrogenase (LDH) levels; (4) platelet morphology; (5) platelet aggregation responsiveness; (6) thromboxane beta-2 (TXB-2) production; (7) dense body secretion; and (8) alpha granule secretion. These assays demonstrated that this photochemical inactivation system inactivated bacteria and viruses in platelet concentrates with minimal adverse effects on the in vitro function of platelets in comparison to untreated control concentrates maintained under current, standard blood bank conditions

  8. Function and platelet count in thrombocyte concentrate (TC during the storage

    Directory of Open Access Journals (Sweden)

    Elida Marpaung

    2016-01-01

    Full Text Available AbstrakLatar belakang: Evaluasi terhadap pemberian transfusi belum dilakukan secara optimal baik di hulumaupun di hilir. Tujuan penelitian ini untuk mengetahui pengaruh waktu penyimpanan terhadap perubahanpH, jumlah trombosit, dan fungsi agregasi yang terjadi pada trombosit pada beberapa hari penyimpanan.Metode: Disain penelitian potong lintang terhadap sample kantong konsentrat trombosit yang yang telahlolos skrining infeksi penyakit menular melalui transfusi darah. Pengujian yang dilakukan ialah terhadappH, jumlah trombosit dan fungsi agregasi terhadap sampel pada tiga waktu pengujian pada hari ke-0, ketiga, dan ke lima penyimpanan.Hasil: Pada 50 sampel kantong konsentrat trombosit didapatkan kenaikan pH pada hari ke tigapenyimpanan kantong trombosit yang disertai penurunan pada hari ke lima. Hal serupa ditemui pulapada jumlah trombosit. Sementara penurunan fungsi agregasi trombosit ditemukan lebih awal pada harike tiga penyimpanan dan didapatkan nilai rendah pada hampir semua sampel.Kesimpulan: Ketiga parameter yaitu pH, jumlah trombosit, dan fungsi agregasi mengalami penurunanpada hari kelima. (Health Science Journal of Indonesia;2015;6:48-51Kata kunci: thrombocyte, concentrate, pH, agregasi, waktu penyimpanan. AbstractBackground: Evaluation for platelet transfusion is not optimal for this moment even in upstream at theblood center or in downstream at the hospital. The purpose of this study was to determine the effect ofstorage time to changes in pH, platelet count and function that occurs on platelet aggregation duringdifferent time storage.Methods: The study design was cross-sectional on selected bags of platelet concentrates that have passedthe screening for infection transmitted through blood transfusions. The regular assessment in UTDD forPC has been done every month by random sampling with three parameters pH, platelets count and volumein the bag of blood. The testing for pH, platelet count, and aggregation functions for 50 samples

  9. Changes in platelet function, blood coagulation and fibrinolysis during insulin-induced hypoglycaemia in juvenile diabetics and normal subjects

    DEFF Research Database (Denmark)

    Dalsgaard-Nielsen, J; Madsbad, S; Hilsted, J

    1982-01-01

    patients were normoglycaemic for at least 10 hr before the study. Platelet aggregation in vitro was induced by lower adenosine diphosphate (ADP) concentrations in the diabetics than in the controls before hypoglycaemia and 0 and 60 min after insulin infusion. Platelet counts decreased significantly in the...

  10. Human platelet 5HT receptors: characterisation and functional association

    International Nuclear Information System (INIS)

    Normal human blood platelets in plasma were incubated at 20C with tritiated 5-hydroxytryptamine ([3H]5HT), and the specific receptor binding was displaced by the addition of unlabelled 5HT. The kinetic parameters of this binding were established and a two-site model for the platelet 5HT receptor demonstrated. Site A has a Ksub(D) of 0.5-1 nM and capacity of 6-10 fmol/108 platelets, and site B a Ksub(D) of 15-36 nM and a capacity of 100-150 fmol/108 platelets. Non-specific or non-receptor binding of [3H]5HT to platelets at 20C was resolved into a passive linear component and an active saturable component sensitive to metabolic inhibition. Binding to the lower affinity 5HT receptor site was inhibited by drugs of the tricylic antidepressant type with IC50 values similar to those against the active uptake component of non-specific binding as described. Isomers of the neuroleptic drug flupenthixol showed a differential and competitive antagonism of high affinity [3H]5HT binding. The 5HT antagonist methysergide, and pizotifen and mianserin also were competitive inhibitors at this site. The rank order of potency of these drugs correlated with their action as inhibitors of 5HT induced platelet aggregation. It is concluded that binding of [3H]5HT to intact human platelets satisfies all the criteria for specific binding and that the two sites demonstrated, of high and lower affinity, are concerned with the functions of 5HT induced aggregation and 5HT uptake respectively. (Auth.)

  11. Estudo farmacognóstico e atividade in vitro sobre a coagulação sanguínea e agregação plaquetária das folhas de Passiflora nitida Kunth (Passifloraceae Pharmacognostic study and in vitro activity on blood coagulation and platelet aggregation of leaves of Passiflora nitida Kunth (Passifloraceae

    Directory of Open Access Journals (Sweden)

    Maria José de Carvalho

    2010-03-01

    fruits of this species by the local population for gastrointestinal disorders. Considering the pharmacological potential of the genus, this work aimed to carry out study of phytochemical characterization of this species and study the effects of the aqueous (AE, ethanol (EE and hexane (HE extracts from its leaves on blood coagulation and platelet aggregation. Thin-layer chromatography and nuclear magnetic resonance were carried out for the phytochemical characterization. The effect of the extracts on the coagulation was evaluated by prothrombin time (PT and activated partial thromboplastin time (aPTT tests. The effect on the platelet aggregation was evaluated in platelet-rich plasma by spectrophotometric method, using adenosine diphosphate (ADP and adrenaline (ADR as inducers of aggregation. The AE, EE and HE extracts showed coagulant activity by the PT test, and the EE showed anticoagulant activity by the aPTT. When induced by ADP, the AE, EE and HE extracts showed 50% inhibitory concentration values (IC50, µg/mL of 450.5 ± 50.7, 511.2 ± 35.5 and 394.4 ± 8.9, respectively, and when induced by ADR showed values of 438.7 ± 5.2, 21.0 ± 1.9 and 546.9 ± 49.9, respectively. The EE showed inhibitory effect on the aggregation. The phytochemical characterization was suggestive of the presence of flavonoids and coumarins, which can be attributed in part to the biological effects studied.

  12. Receptor-mediated effects of a PGH2 analogue (U 46619) on human platelets

    International Nuclear Information System (INIS)

    The specific effects of U 46619 (9,11-dideoxy,9α-11α-methanoepoxy-prostaglandin F2α), thromboxane A2-prostaglandin H2 (TxA2/PGH2) analogue, on human platelet shape change, myosin light-chain phosphorylation, serotonin release, fibrinogen receptor exposure, and platelet aggregation were measured and compared with binding of [3H]U 46619 to platelets. Shape change and myosin light-chain phosphorylation were found to be saturable and dose dependent. These two effects were competitively inhibited by specific antagonists of TxA2/PGH2 receptors indicating that they are receptor mediated. Binding of [3H]U 46619 showed two components. The authors proposed that a second component represents a second, low-affinity site. Mean EC50 values for U 46619-induced serotonin release platelet aggregation, and fibrinogen receptor exposure were 0.54 ± 0.13, 1.31 ± 0.34, and 0.53 ± 0.21 μM, respectively. Therefore, the platelet release reaction was not directly correlated with occupancy of high-affinity receptors but could be related to the second binding component of U 46619. Fibrinogen receptor exposure and platelet aggregation caused by U 46619 appeared to be events mediated by the release of adenosine diphosphate from platelet-dense granules

  13. Prophylactic platelets in dengue

    DEFF Research Database (Denmark)

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

    2012-01-01

    Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage. As a...... result of this prophylactic platelet transfusions are sometimes advocated for the prevention of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a global survey to assess the different approaches to the use of...... platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity of...

  14. Role of Platelets in Thromboembolism in Patients with Atrial Fibrillation.

    Science.gov (United States)

    Gosk-Bierska, Izabela; Wasilewska, Marta; Wysokiński, Waldemar

    2016-01-01

    Thromboembolic complications of atrial fibrillation (AF) are a major cause of morbidity and mortality but the mechanism of its process remain poorly understood. There are many as yet unanswered questions surrounding the increased thrombotic tendency in AF. One of the crucial questions is what determines the fact that a thrombus remains in the left atrium in situ in some patients, while in others it breaks off and leads to embolic complications. Recent studies indicated an important role of platelets in the left atrial's thrombus formation and suggest that the embolic potential of left atrial thromboses depends on the involvement of platelets in the process of fibrin stabilization rather than aggregation. New methods for investigating platelets function, such as the analysis of transcription activity of RNA coming from platelets contained in thrombi formed in AF, creates an opportunity for studying populations of platelets that are directly involved in homeostatic clot formation. In this paper we present current opinions on the participation of platelets in the pathogenesis of thromboembolism in patients with AF. PMID:26935511

  15. Three-dimensional multi-scale model of deformable platelets adhesion to vessel wall in blood flow.

    Science.gov (United States)

    Wu, Ziheng; Xu, Zhiliang; Kim, Oleg; Alber, Mark

    2014-08-01

    When a blood vessel ruptures or gets inflamed, the human body responds by rapidly forming a clot to restrict the loss of blood. Platelets aggregation at the injury site of the blood vessel occurring via platelet-platelet adhesion, tethering and rolling on the injured endothelium is a critical initial step in blood clot formation. A novel three-dimensional multi-scale model is introduced and used in this paper to simulate receptor-mediated adhesion of deformable platelets at the site of vascular injury under different shear rates of blood flow. The novelty of the model is based on a new approach of coupling submodels at three biological scales crucial for the early clot formation: novel hybrid cell membrane submodel to represent physiological elastic properties of a platelet, stochastic receptor-ligand binding submodel to describe cell adhesion kinetics and lattice Boltzmann submodel for simulating blood flow. The model implementation on the GPU cluster significantly improved simulation performance. Predictive model simulations revealed that platelet deformation, interactions between platelets in the vicinity of the vessel wall as well as the number of functional GPIbα platelet receptors played significant roles in platelet adhesion to the injury site. Variation of the number of functional GPIbα platelet receptors as well as changes of platelet stiffness can represent effects of specific drugs reducing or enhancing platelet activity. Therefore, predictive simulations can improve the search for new drug targets and help to make treatment of thrombosis patient-specific. PMID:24982253

  16. Variability in platelet responses to collagen--comparison between whole blood perfusions, traditional platelet function tests and PFA-100.

    Science.gov (United States)

    Lepäntalo, A; Beer, J H; Siljander, P; Syrjälä, M; Lassila, R

    2001-07-15

    The purpose of this study was to determine if the results obtained in platelet function tests and whole blood perfusions are associated with those in platelet function analyser (PFA)-100. We used collagen type I monomers and fibrils to analyse the distinct roles of glycoprotein (GP) Ia/IIa and other collagen receptors in flowing blood under a high shear rate (1600/s) and in aggregation studies. Also, anticoagulation [citrate vs. D-phenylalanyl-1-prolyl-1 arginine chloromethyl ketone (PPACK)] was varied to enhance the functions of GP Ia/IIa, since it has been shown that the cation-poor environment of citrated blood impairs GP Ia/IIa-dependent platelet recruitment. Large interindividual variability (45-fold) was detected in deposition of platelets in whole blood perfusions over collagen monomers, whereas this variation was only fourfold in fibrils. In PFA, this variation was reduced to 2.5-fold. However, platelet deposition on monomers is associated with epinephrine-enhanced PFA (r=-.49, P<.03), whereas platelet deposition on fibrils is correlated with adenosine diphosphate (ADP)-enhanced PFA (r=-.47, P<.05), suggesting a distinct synergism between epinephrine and monomers (GP Ia/IIa) as well as ADP with fibrils (other collagen receptors). Donors with 807 C/C polymorphism of GP Ia (n=14) had longer lag phase in aggregation experiments compared with C/T (n=7) both by monomers and fibrils (P<.04), but these polymorphisms with their mild impact on GP Ia/IIa activity did not markedly differ in other tests. In conclusion, the results obtained in perfusion studies and PFA experiments correlated, but PFA fails to reveal the large-scale variability related to collagen-induced platelet responses. PMID:11457470

  17. Platelet and monocyte activity markers and mediators of inflammation in Takotsubo cardiomyopathy.

    Science.gov (United States)

    Pirzer, Rainer; Elmas, Elif; Haghi, Dariusch; Lippert, Christiane; Kralev, Stefan; Lang, Siegfried; Borggrefe, Martin; Kälsch, Thorsten

    2012-03-01

    Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t(0)), after 2-4 days (t(1)) and after 4-7 weeks (t(2)), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2-4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC. PMID:21416113

  18. Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species†

    Science.gov (United States)

    Yuan, Hengjie; Houck, Katie L.; Tian, Ye; Bharadwaj, Uddalak; Hull, Ken; Zhou, Zhou; Zhou, Mingzhao; Wu, Xiaoping; Tweardy, David J.; Romo, Daniel; Fu, Xiaoyun; Zhang, Yanjun; Zhang, Jianning; Dong, Jing-fei

    2015-01-01

    Background Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known. Objective We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen. Results PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect. Conclusions PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals. PMID:26645674

  19. Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species.

    Directory of Open Access Journals (Sweden)

    Hengjie Yuan

    Full Text Available Piperlongumine (PL is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known.We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen.PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect.PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals.

  20. Aggregate productivity and aggregate technology

    OpenAIRE

    Susanto Basu; John G. Fernald

    1997-01-01

    Aggregate productivity and aggregate technology are meaningful but distinct concepts. We show that a slightly-modified Solow productivity residual measures changes in economic welfare, even when productivity and technology differ because of distortions such as imperfect competition. We then present a general accounting framework that identifies several new non-technological gaps between productivity and technology, gaps reflecting imperfections and frictions in output and factor markets. Empi...

  1. Clinical significance on changes of platelet aggregation test, von Willebrand factor,antithrombin and D-dimer assayin acute cerebral infarction patients%急性脑梗死患者血小板聚集功能、血管性血友病因子、抗凝血酶及 D-二聚体测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    叶青跃; 程鹏飞; 周有利; 饶汉武; 黄承芳; 周立

    2015-01-01

    目的:探讨急性脑梗死患者血小板聚集功能( PAgT)、血管性血友病因子( vWF)、抗凝血酶( AT)和D-二聚体( D-dimer)水平变化及临床意义。方法选用相应的方法和仪器测定112例脑梗死及80例健康对照者血(浆) PAgT、vWF、AT和D-dimer水平变化,同时对部分患者进行治疗前、后的对比分析。结果脑梗死患者血中PAgT、vWF、D-dimer等指标均明显高于健康对照组,AT活性较对照组显著降低,差异有统计学意义(P<0.05或P<0.01)。选取经治疗效果明显好转的78例脑梗死患者,出院前取空腹静脉血测定PAgT、vWF、AT、D-dimer等指标,并与治疗前对照,结果治疗后PAgT、vWF、D-dimer降低,AT活性升高,差异有统计学意义(P<0.05或P<0.01)。结论脑梗死患者体内存在明显的凝血及纤溶功能异常,与血管内皮损伤、血小板聚集功能增强、凝血及纤溶功能亢进、抗凝功能降低等多因素有关。 PAgT、vWF、AT、D-dimer可以作为脑梗死患者诊断、治疗监测和预后判断的参考指标。%Objective To evaluate the clinical signification of coagulation ,anti-coagulation and fibrinolysis indexes i.e.platelet aggrega-tion test(PAgT),von Willebrand factor(vWF),antithrombin(AT),D-dimer in acute cerebral infarction patients.Methods vWF was as-sayed using ELISA method,AT was determined by chromogenic substances assay,and Latex enhanced immune turbidimetry for D-dimer. vWF,AT and D-dimer all the parameters were finished by SysmexCA-7000 automated blood coagulation analyzer.PAgT was measured sim-ultaneously using a whole-blood Lumi-Aggregometer by CHRMNO-LOG platelet aggregation apparatus.Results PAgT, vWF, D-dimer were significantly higher in acute cerebral infarction patients group,compared with those in the control group(P<0.05 or P<0.01). while AT was significantly lower(P<0.05).After effective treatment,PAgT,vWF,AT,D-dimer Indicators are all

  2. Platelet P2Y12 is involved in murine pulmonary metastasis.

    Directory of Open Access Journals (Sweden)

    Yanhua Wang

    Full Text Available The involvement of platelets in tumor progression is well recognized. The depletion of circulating platelets or pharmacologic inhibitors of platelet activation decreases the metastatic potential of circulating tumor cells in metastasis mouse models. The platelet ADP receptor P2Y12 amplifies the initial hemostatic responses activated by a variety of platelet agonists and stabilizes platelet aggregation, playing a crucial role in granule secretion, integrin activation and thrombus formation. However, the relationship between P2Y12 and tumor progression is not clear. In our study, the Lewis Lung Carcinoma (LLC spontaneous metastatic mouse model was used to evaluate the role of P2Y12 in metastasis. The results demonstrated that P2Y12 deficiency significantly reduced pulmonary metastasis. Further studies indicated that P2Y12 deficiency diminished the ability of LLC cells to induce platelet shape change and release of active TGFβ1 by a non-contact dependent mechanism resulting in a diminished, platelet-induced EMT-like transformation of the LLC cells, and that transformation probably is a prerequisite of LLC cell metastasis. Immunohistochemical analyses indicated an obvious P2Y12 deficiency related attenuation of recruitment of VEGFR1+ bone marrow derived cell clusters, and extracellular matrix fibronectin deposition in lungs, which presumably are required for pre-metastatic niche formation. In contrast to the LLC cells, non-epithelial melanoma B16 cells induced platelet aggregation in a cell number and P2Y12-dependent manner. Also, a platelet induced EMT-like transformation of B16 cells is dependent on P2Y12. In agreement with the LLC cell model, platelet P2Y12 deficiency also results in significantly less lung metastasis in the B16 melanoma experimental metastasis model. These results demonstrate that P2Y12 is a safe drug target for anti-thrombotic therapy, and that P2Y12 may serve as a new target for inhibition of tumor metastasis.

  3. Brazilin isolated from Caesalpinia sappan L. acts as a novel collagen receptor agonist in human platelets

    Directory of Open Access Journals (Sweden)

    Chang Yi

    2013-01-01

    Full Text Available Abstract Background Brazilin, isolated from the heartwood of Caesalpinia sappan L., has been shown to possess multiple pharmacological properties. Methods In this study, platelet aggregation, flow cytometry, immunoblotting analysis, and electron spin resonance (ESR spectrometry were used to investigate the effects of brazilin on platelet activation ex vivo. Moreover, fluorescein sodium-induced platelet thrombi of mesenteric microvessels was also used in in vivo study. Results We demonstrated that relatively low concentrations of brazilin (1 to 10 μM potentiated platelet aggregation induced by collagen (0.1 μg/ml in washed human platelets. Higher concentrations of brazilin (20 to 50 μM directly triggered platelet aggregation. Brazilin-mediated platelet aggregation was slightly inhibited by ATP (an antagonist of ADP. It was not inhibited by yohimbine (an antagonist of epinephrine, by SCH79797 (an antagonist of thrombin protease-activated receptor [PAR] 1, or by tcY-NH2 (an antagonist of PAR 4. Brazilin did not significantly affect FITC-triflavin binding to the integrin αIIbβ3 in platelet suspensions. Pretreatment of the platelets with caffeic acid phenethyl ester (an antagonist of collagen receptors or JAQ1 and Sam.G4 monoclonal antibodies raised against collagen receptor glycoprotein VI and integrin α2β1, respectively, abolished platelet aggregation stimulated by collagen or brazilin. The immunoblotting analysis showed that brazilin stimulated the phosphorylation of phospholipase C (PLCγ2 and Lyn, which were significantly attenuated in the presence of JAQ1 and Sam.G4. In addition, brazilin did not significantly trigger hydroxyl radical formation in ESR analysis. An in vivo mouse study showed that brazilin treatment (2 and 4 mg/kg significantly shortened the occlusion time for platelet plug formation in mesenteric venules. Conclusion To the best of our knowledge, this study provides the first evidence that brazilin acts a novel collagen

  4. Calpain Activity and Toll-Like Receptor 4 Expression in Platelet Regulate Haemostatic Situation in Patients Undergoing Cardiac Surgery and Coagulation in Mice

    Directory of Open Access Journals (Sweden)

    Jui-Chi Tsai

    2014-01-01

    Full Text Available Human platelets express Toll-like receptors (TLR 4. However, the mechanism by which TLR4 directly affects platelet aggregation and blood coagulation remains to be explored. Therefore, in this study, we evaluated the platelet TLR4 expression in patients who underwent CABG surgery; we explored the correlation between platelet TLR4 expression and the early outcomes in hospital of patients. Additionally, C57BL/6 and C57BL/6-TlrLPS−/− mice were used to explore the roles of platelet TLR4 in coagulation by platelet aggregometry and rotation thromboelastometry. In conclusion, our results highlight the important roles of TLR4 in blood coagulation and platelet function. Of clinical relevance, we also explored novel roles for platelet TLR4 that are associated with early outcomes in cardiac surgery.

  5. Dependence of plasmin-mediated degradation of platelet adhesive receptors on temperature and Ca2+

    International Nuclear Information System (INIS)

    The effects of activation of plasminogen by streptokinase and tissue-type-plasminogen activator on platelet activation and the membrane glycoproteins (GPs) that mediate platelet adhesion and aggregation are not yet fully defined. To clarify effects on platelets during activation of plasminogen in vitro, we used monoclonal antibodies (MoAbs), flow cytometry, and platelets surface-labeled with 125I to characterize changes in receptors for fibrinogen (GPIIb-IIIa), von Willebrand factor (GPIb), and collagen (GPIa-IIa). Activation of plasminogen in plasma with pharmacologic concentrations of plasminogen activators did not degrade GPIIb-IIIa or GPIb, and caused only a modest decrease in GPIa. In washed platelets GPIIb-IIIa was extensively degraded by plasmin at 37 degrees C in the absence of exogenous Ca2+, conditions that destabilize the IIb-IIIa complex. Degradation of GPIb in washed platelets displayed a similar although less-marked dependence on temperature and the absence of Ca2+. The binding of activation-specific MoAbs did not increase during activation of plasminogen in plasma. We conclude that during pharmacologic fibrinolysis, reported inhibition of platelet function in plasma is not due to degradation of platelet-adhesive receptors. In addition, platelet activation observed during thrombolytic therapy does not appear to be a direct consequence of plasminogen activation

  6. Lactodifucotetraose, a human milk oligosaccharide, attenuates platelet function and inflammatory cytokine release.

    Science.gov (United States)

    Newburg, David S; Tanritanir, Ayse C; Chakrabarti, Subrata

    2016-07-01

    Human milk strongly quenches inflammatory processes in vitro, and breastfed infants have lower incidence of inflammatory diseases than those fed artificially. Platelets from neonates, in contrast to those from adults, are less responsive to platelet agonists such as collagen, thrombin, ADP, and epinephrine. Breastfed infants absorb oligosaccharides intact from the human milk in their gut to the circulation. This study was to determine whether these oligosaccharides can attenuate platelet function and platelet secretion of pro-inflammatory proteins, and to identify the active component. The natural mixture of oligosaccharides from human milk and pure individual human milk oligosaccharides were tested for their ability to modulate responses of platelets isolated from human blood following exposure to thrombin, ADP, and collagen. Human milk and the natural mixture of human milk oligosaccharides inhibited platelet release of inflammatory proteins. Of the purified human milk oligosaccharides tested, only lactodifucotetraose (LDFT) significantly inhibited thrombin induced release of the pro-inflammatory proteins RANTES and sCD40L. LDFT also inhibited platelet adhesion to a collagen-coated surface, as well as platelet aggregation induced by ADP or collagen. These data indicate that LDFT may help modulate hemostasis by suppressing platelet-induced inflammatory processes in breastfed infants. This activity suggests further study of LDFT for its potential as a therapeutic agent in infants and adults. PMID:26743063

  7. P-selectin-mediated platelet adhesion promotes the metastasis of murine melanoma cells.

    Directory of Open Access Journals (Sweden)

    Cui-Ling Qi

    Full Text Available Studies have indicated that the aggregation of activated platelets with cancer cells facilitates tumor metastasis; the adhesion molecule P-selectin may be an important mediator of this process, but the detailed mechanism is unclear. In the current study, we established a B16F10 (B16 cell metastatic model in P-selectin knockout (P-sel-/- mice to determine the effect of P-selectin-mediated platelet adhesion on metastasis. Compared with C57 mice, P-sel-/- mice developed fewer metastatic foci, and cell proliferation within the metastatic tumors was inhibited by P-selectin deficiency. The platelet refusion assay demonstrated that mice with P-sel-/- platelets developed fewer lung metastatic foci (P<0.01 with a lower microvascular density (MVD than mice with wild-type platelets. A co-culture model of platelets and B16 cells was utilized to determine the difference in VEGF concentration in the supernatants. The results demonstrated that the supernatant from the P-sel-/- platelet/B16 co-culture had a lower concentration of VEGF. Therefore, our findings indicated that P-selectin deficiency inhibited the metastasis of B16 cells and that wild-type platelet refusion reversed this inhibition. The P-selectin-mediated interaction between platelets and B16 cells promoted angiogenesis by up-regulating VEGF.

  8. Aspirin has little additional anti-platelet effect in healthy volunteers receiving prasugrel

    OpenAIRE

    LEADBEATER, P D M; Kirkby, N S; Thomas, S.(Rutgers, The State University of New Jersey, Piscataway, USA); DHANJI, A-R; Tucker, A T; MILNE, G L; Mitchell, J. A.; Warner, T D

    2011-01-01

    Summary Background: Strong P2Y12 blockade, as can be achieved with novel anti-platelet agents such as prasugrel, has been shown in vitro to inhibit both ADP and thromboxane A2-mediated pathways of platelet aggregation, calling into question the need for the concomitant use of aspirin. Objective: The present study investigated the hypothesis that aspirin provides little additional anti-aggregatory effect in a group of healthy volunteers taking prasugrel. Study participants/methods: In all, 9 m...

  9. Effect of the platelet membrane GP Ⅰ a gene polymorphism in the pathogenesis of unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    Yonghui Zhao; Changcong Cui; Yanni Wang; Jiaqing Zhu

    2005-01-01

    Objective: To investigate the effect of platelet membrane glycoprotein(GP) Ⅰ a gene polymorphism in the pathogenesis of unstable angina pectoris (UAP) in Chinese people. Methods: Collagen type Ⅰ -induced platelet aggregation was measured in 33healthy subjects in vitro. Plasma level of α-granule membrane protein (GMP-140) was measured in both the above 33 healthy subjects during fasting and 35 patients with recent onset effort anina during rest onset within 24 h after hospitalization. Furthermore, the platelet membrane GP Ⅰ a gene 807C/T polymorphism was checked in all subjects with polymerase chain reaction-sequence specific primers(PCR-SSP)technique. Results: The lag time before 30% platelet aggregation was significantly longer in healthy subjects with CC genotype than with TC genotype ( P <0.01). However, there was no significant difference in the maximal platelet aggregation between healthy subjects with the above two genotypes. Plasma level of GMP-140 was significantly higher in TC genotypic patients with recent onset effort angina than in CC genotypic patients with the same type of UAP( P < 0.05) and healthy subjects ( P < 0.01), furthermore, there was also significant difference between the latter two groups( P < 0.05). Conclusion: The rapid initiation of collagen-induced platelet aggregation may be associated with platelet membrane GP Ⅰ a T807 allele, which may play an important role in the pathogenesis of UAP.

  10. UVB radiation exposes fibrinogen binding sites on platelets by activating protein kinase C via reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Kooy, M. van M.; Akkerman, J.W.N.; Asbeck, S. van; Borghuis, Lizette; Prooijen, H.C. van (Utrecht Univ. Hospital (Netherlands))

    1993-02-01

    In the present study the authors have further investigated the routes of platelet activation following UVB exposure. Evidence is provided that UVB radiation does not activate the platelets via the classical Phospholipase A[sub 2] and Phospholipase C routes. Despite this observation, UVB-induced fibrinogen binding was found to be correlated with a 40% increase in phosphorylated 47 kD protein. Both findings could be completely inhibited in the presence of staurosporine, a potent inhibitor of protein kinase C (PK-C). In efforts to explain the mechanism of PK-C activation by UV radiation they found that both UV-induced PK-C activation and platelet aggregation were significantly reduced in the presence of specific scavengers for reactive oxygen species including superoxide dismutase and catalase. It is concluded that exposure of platelets to UVB radiation can activate PK-C via oxygen radicals, resulting in exposure of fibrinogen binding sites and subsequent platelet aggregation. (Author).

  11. Effects of Total Flavone of Abelmoschl Manihot L. Medic on the Function of Platelets and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    GUO Yan; FAN Li; DONG Liu-yi; CHEN Zhi-wu

    2005-01-01

    Objective:To study the effects of total flavone of Abelmoschl Manihot L. Medic (TFA) on the function of platelets and to explore its mechanism. Methods: Rat models of artery-veins bypassing thrombus formation were used. The platelets of rabbits were collected. Platelet aggregation was induced by collagen and intracellular calcium ion concentration ([Ca2+ ]i) was assayed by Fura-2 method. Results: TFA (25, 50,100 mg/kg) significantly and dose-dependently reduced the weight of thrombus. TFA (0. 025, 0.05, 0.1 mg/mi) possessed dose-dependant inhibitory effects on rabbits' platelet aggregation induced by collagen. TFA significantly reduced the resting and CaCl2-induced increase of free intracellular calcium concentration ([Ca2+ ]i) in rabbit platelet in vitro. Conclusion: TFA has an antiplatelet effect via the inhibition on the influx of Ca2+ .

  12. Fibrinogen concentrate improves clot strength in patients with haematological malignancies requiring platelet transfusion

    DEFF Research Database (Denmark)

    Munk-Andersen, H; Schenk, B; Larsen, O H;

    2016-01-01

    BACKGROUND: Patients with bone marrow failure secondary to chemotherapy often develop thrombocytopenia and require platelet transfusion. Fibrinogen plays an important role in platelet aggregation and the establishment of the primary haemostatic plug. OBJECTIVES: To compare the effects of in vivo...... platelet transfusion on clot firmness in thrombocytopenic patients with in vitro-performed fibrinogen concentrate substitution. MATERIALS AND METHODS: Thirty patients with haematological malignancy admitted for platelet transfusion were included. Haemostatic effects from platelet transfusion and ex vivo...... addition of fibrinogen concentrate at three different doses were evaluated by thromboelastometry, with clot firmness as the primary endpoint (A30 ExTEM assay). Secondary endpoints were other thromboelastometry parameters, thrombin generation parameters, activated partial thromboplastin time (APTT...

  13. Effect of adhesion proteins and surface chemistry on the procoagulant state of adherent platelets

    Science.gov (United States)

    Grunkemeier, John Mark

    Poor hemocompatibility of a blood contacting device can lead to blood clotting, reduced blood flow, and depletion of platelets from the blood. Improved understanding of the processes by which blood-material contact leads to these responses could result in more hemocompatible materials. Platelets accelerate blood clotting by adhesion, aggregation, secretion of proteins and agonists and acceleration of thrombin generation. Platelets are said to be "procoagulant" after phosphatidylserine residues flip from the cytosolic to the extracellular face of the lipid bilayer. This then allows for the assembly of the prothrombinase complex (Xa, Va and calcium) on the platelet membrane, which can rapidly convert prothrombin to thrombin. In this study, three different methods confirmed that adhesion causes platelets to become procoagulant: shortening of clotting times of recalcified plasma, binding of FITC-annexin V, and generation of thrombin in the presence of Va, Xa and prothrombin by adherent platelets. Adherent platelets were 10--23 times more activated than bulk phase unactivated platelets and 10--24 times less activated than bulk phase platelets activated by calcium ionophore. The role of adsorbed fibrinogen, vWF, mixtures of fibrinogen and vWF, fibronectin, whole and dilute plasma, and plasma deficient in adhesion proteins in stimulating platelet procoagulant activity was investigated. The results of these experiments suggested that adhesion proteins affect procoagulant activation to varying degrees and that surfaces preadsorbed with mixtures of adhesion proteins are more activating that surfaces preadsorbed with single adhesion proteins. The hypothesis that materials that affect tightness of binding of adsorbed adhesion proteins affect platelet procoagulant activity was investigated. These studies showed that increasing fluorine content of RFGD polymerized films caused reduced platelet adhesion, but increased procoagulant activity, possibly due to their ability to adsorb

  14. Thrombocytopenia model with minimal manipulation of blood cells allowing whole blood assessment of platelet function.

    Science.gov (United States)

    Tiedemann Skipper, Mette; Rubak, Peter; Halfdan Larsen, Ole; Hvas, Anne-Mette

    2016-06-01

    In vitro models of thrombocytopenia are useful research tools. Previously published models have shortcomings altering properties of platelets and other blood components. The aim of the present study was to develop a whole blood method to induce thrombocytopenia with minimal manipulation, and to describe platelet function in induced thrombocytopenia in individuals with healthy platelets. Hirudin anticoagulated blood was obtained from 20 healthy volunteers. One part of the blood was gently centrifuged at 130g for 15 minutes. The platelet-rich plasma was replaced with phosphate-buffered saline to establish thrombocytopenia. Various levels of thrombocytopenia were achieved by combining different volumes of baseline whole blood and thrombocytopenic blood. Platelet counts were measured by flow cytometry (Navios, Beckman Coulter) and routine haematological analyser (Sysmex XE-5000). Platelet function was analysed by impedance aggregometry (Multiplate® Analyzer, Roche) and by flow cytometry (Navios, Beckman Coulter) using collagen, adenosine diphosphate, thrombin receptor activating peptide-6 and ristocetin as agonists. Median baseline platelet count was 227×10(9)/l. The in vitro model yielded median platelet counts at 51×10(9)/l (range 26-93×10(9)/l). We observed minor, yet significant, changes in platelet size and maturity from baseline to modelled thrombocytopenia. In the thrombocytopenic samples, significant and positive linear associations were found between platelet count and platelet aggregation across all agonists (all p-valuesblood-based model of thrombocytopenia was established and validated. This new model serves as a useful future tool, particularly to explore platelet function in patients with thrombocytopenia. PMID:26555800

  15. Human platelet calmodulin-binding proteins: identification and Ca/sup 2 +/-dependent proteolysis upon platelet activation

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, R.W.; Tallant, E.A.; McManus, M.C.

    1987-05-19

    Calmodulin-binding proteins have been identified in human platelets by using Western blotting techniques and /sup 125/I-calmodulin. Ten distinct proteins of 245, 225, 175, 150, 90, 82 (2), 60, and 41 (2) kilodaltons (kDa) bound /sup 125/I-calmodulin in a Ca/sup 2 +/-dependent manner; the binding was blocked by ethylene glycol bis(..beta..-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), trifluoperazine, and nonradiolabeled calmodulin. Proteins of 225 and 90 kDa were labeled by antisera against myosin light chain kinase; 60- and 82-kDa proteins were labeled by antisera against the calmodulin-dependent phosphatase and caldesmon, respectively. The remaining calmodulin-binding proteins have not been identified. Calmodulin-binding proteins were degraded upon addition of Ca/sup 2 +/ to a platelet homogenate; the degradation could be blocked by either EGTA, leupeptin, or N-ethylmaleimide which suggests that the degradation was due to a Ca/sup 2 +/-dependent protease. Activation of intact platelets by thrombin, adenosine 5'-diphosphate, and collagen under conditions which promote platelet aggregation also resulted in limited proteolysis of calmodulin-binding proteins including those labeled with antisera against myosin light chain kinase and the calmodulin-dependent phosphatase. Activation by the Ca/sup 2 +/ ionophores A23187 and ionomycin also promoted degradation of the calmodulin-binding proteins in the presence of extracellular Ca/sup 2 +/. The data indicate that limited proteolysis of Ca/sup 2 +//calmodulin-regulated enzymes also occurs in the intact platelet and suggest that the proteolysis is triggered by an influx of extracellular Ca/sup 2 +/ associated with platelet aggregation.

  16. The influence of herbal medicine on platelet function and coagulation: a narrative review.

    Science.gov (United States)

    McEwen, Bradley J

    2015-04-01

    Cardiovascular disease (CVD) is the leading cause of death worldwide. Platelet activation and aggregation play a central role in hemostasis and thrombosis. Herbal medicines have been traditionally used in the management of CVD and can play a role in modifying CVD progression, particularly in platelet function, and have the potential of altering platelet function tests, as well as some coagulation parameters. Herbal medicines, such as feverfew, garlic, ginger, ginseng, motherwort, St John's wort, and willow bark, were found to reduce platelet aggregation. In vitro studies show promise in the reduction of platelet aggregation for Andrographis, feverfew, garlic, ginger, Ginkgo, ginseng, hawthorn, horse chestnut, and turmeric. In addition, cranberry, danshen, dong quai, Ginkgo, ginseng, green tea, and St John's wort were found to have potential interactions with warfarin. Furthermore, St John's wort interacted with clopidogrel and danshen with aspirin. Therefore, repeat testing of platelet function and coagulation studies, particularly for patients on warfarin therapy, may be required after exclusion of herbal medicines that could have possibly affected initial test results. PMID:25839871

  17. Identification of D1-like dopamine receptors on human blood platelets

    International Nuclear Information System (INIS)

    Dopamine is able to inhibit the epinephrine-induced aggregation of human blood platelets, but the mechanism of action has not been elucidated. In this study the authors report that membranes from human blood platelets possess high affinity, saturable and stereoselective binding sites for the D1 dopamine receptor antagonist (3H)SCH 23390. (3H)SCH 23390 appeared to label a single class of binding sites with a B/sub max/ of 18.6 +- 1.6 fmolmg protein and a K/sub D/ of 0.8 nM. The potencies of different dopaminergic antagonists and agonists in displacing (3H)SCH 23390 from blood platelet membranes were similar to those obtained for striatal membranes. Unlike the classically defined D1 receptors, e.g. those in striatum, the D1 receptor sites on platelets appeared no to be coupled to the adenylate cyclase system, hence the term D1-like. The D1 agonist SKF 38393 was more potent than dopamine in inhibiting platelet aggregation induced by epinephrine, and the effects of dopamine and SKF 38393 were prevented by SCH 23390. These results suggest that the inhibitory action of dopamine on the epinephrine-induced platelet aggregation is mediated through these D1-like receptors

  18. A novel role of sesamol in inhibiting NF-κB-mediated signaling in platelet activation

    Directory of Open Access Journals (Sweden)

    Chang Chao-Chien

    2011-12-01

    Full Text Available Abstract Background Platelet activation is relevant to a variety of coronary heart diseases. Our previous studies revealed that sesamol possesses potent antiplatelet activity through increasing cyclic AMP formation. Although platelets are anucleated cells, they also express the transcription factor, NF-κB, that may exert non-genomic functions in platelet activation. Therefore, we further investigated the inhibitory roles of sesamol in NF-κB-mediated platelet function. Methods Platelet aggregation, Fura 2-AM fluorescence, and immunoblotting analysis were used in this study. Results NF-κB signaling events, including IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation, were markedly activated by collagen (1 μg/ml in washed human platelets, and these signaling events were attenuated by sesamol (2.5~25 μM. Furthermore, SQ22536 and ODQ, inhibitors of adenylate cyclase and guanylate cyclase, respectively, strongly reversed the sesamol (25 μM-mediated inhibitory effects of IKKβ phosphorylation, IκBα degradation, and p65 phosphorylation stimulated by collagen. The protein kinase A (PKA inhibitor, H89, also reversed sesamol-mediated inhibition of IκBα degradation. Moreover, BAY11-7082, an NF-κB inhibitor, abolished IκBα degradation, phospholipase C (PLCγ2 phosphorylation, protein kinase C (PKC activation, [Ca2+]i mobilization, and platelet aggregation stimulated by collagen. Preincubation of platelets with the inhibitors, SQ22536 and H89, both strongly reversed sesamol-mediated inhibition of platelet aggregation and [Ca2+]i mobilization. Conclusions Sesamol activates cAMP-PKA signaling, followed by inhibition of the NF-κB-PLC-PKC cascade, thereby leading to inhibition of [Ca2+]i mobilization and platelet aggregation. Because platelet activation is not only linked to hemostasis, but also has a relevant role in inflammation and metastasis, our data demonstrating that inhibition of NF-κB interferes with platelet function may

  19. Dipyridamole: pharmacokinetics and effects on aspects of platelet function in man.

    OpenAIRE

    Gregov, D; Jenkins, A.; Duncan, E.; Siebert, D; Rodgers, S; Duncan, B.; Bochner, F; Lloyd, J.

    1987-01-01

    1. The effect of dipyridamole on platelet function was measured in twelve normal subjects given 150 or 200 mg tablets as single and multiple doses, and in six subjects given single doses of 25, 50 and 100 mg and multiple doses of 50 mg 8 hourly. 2. Platelet aggregation was measured in response to ADP and collagen. In the subjects given 150/200 mg, the platelets were assayed for content of cyclic AMP and for formation of thromboxane after addition of collagen. The responses to ADP and collagen...

  20. Important role of platelets in modulating endotoxin-induced lung inflammation in CFTR-deficient mice.

    Directory of Open Access Journals (Sweden)

    Caiqi Zhao

    Full Text Available Mutation of CFTR (cystic fibrosis transmembrane conductance regulator leads to cystic fibrosis (CF. Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels. Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1, platelet activating factor (PAF, and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF, or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients.

  1. Methods to Determine the Lagrangian Shear Experienced by Platelets during Thrombus Growth

    Science.gov (United States)

    Pinar, Isaac P.; Arthur, Jane F.; Andrews, Robert K.; Gardiner, Elizabeth E.; Ryan, Kris; Carberry, Josie

    2015-01-01

    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. PMID:26660525

  2. Studies on the actin-binding protein HS1 in platelets

    Directory of Open Access Journals (Sweden)

    Auger Jocelyn M

    2007-11-01

    Full Text Available Abstract Background The platelet cytoskeleton mediates the dramatic change in platelet morphology that takes place upon activation and stabilizes thrombus formation. The Arp2/3 complex plays a vital role in these processes, providing the protrusive force for lamellipodia formation. The Arp2/3 complex is highly regulated by a number of actin-binding proteins including the haematopoietic-specific protein HS1 and its homologue cortactin. The present study investigates the role of HS1 in platelets using HS1-/- mice. Results The present results demonstrate that HS1 is not required for platelet activation, shape change or aggregation. Platelets from HS1-/- mice spread normally on a variety of adhesion proteins and have normal F-actin and Arp2/3 complex distributions. Clot retraction, an actin-dependent process, is also normal in these mice. Platelet aggregation and secretion is indistinguishable between knock out and littermates and there is no increase in bleeding using the tail bleeding assay. Conclusion This study concludes that HS1 does not play a major role in platelet function. It is possible that a role for HS1 is masked by the presence of cortactin.

  3. 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.

  4. Procoagulant platelet balloons: evidence from cryopreparation and electron microscopy.

    Science.gov (United States)

    Hess, M W; Siljander, P

    2001-05-01

    Visualisation of the procoagulant transformation of human platelets has recently become possible through use of an in vitro approach combined with fluorescence and phase contrast microscopy. Here, we extended these studies to the ultrastructural level by employing both rapid freezing/freeze-substitution and conventional ambient-temperature chemical fixation for transmission and scanning electron microscopy. Procoagulant transformation was only inducible by adhering platelets to collagen fibrils or to the collagen-related peptide and exposing them to physiological extracellular Ca2+ levels. Under these conditions prominent, 2- to 4-micron-wide balloon-like structures were regularly observed, regardless of the specimen fixation protocol. In strong contrast to normal platelets in their vicinity, the balloons' subcellular architecture proved remarkably poor: dilute cytoplasm, no cytoskeleton, only a few, randomly distributed organelles and/or their remnants. Cryofixed balloons displayed intact and smooth surfaces whereas conventional specimen processing caused plasma membrane perforations and shrinkage of the balloons. Our results clearly show that neither the balloons themselves, nor their simple ultrastructure reflect fixation artefacts caused by inadequate membrane stabilisation. The balloons are interpreted as to be transformed and/or fragmented procoagulant platelets. Thus, the generation of balloons represents a genuine, final stage of platelet ontogenesis, presumably occurring alternatively to aggregate formation. PMID:11449892

  5. Ultraviolet irradiation of platelet concentrates: Feasibility in transfusion practice

    Energy Technology Data Exchange (ETDEWEB)

    Andreu, G.; Boccaccio, C.; Lecrubier, C.; Fretault, J.; Coursaget, J.; LeGuen, J.P.; Oleggini, M.; Fournel, J.J.; Samama, M. (Secteur d' Hemobiologie Transfusion, Paris (France))

    1990-06-01

    Ultraviolet (UV)-B irradiation abolishes lymphocyte functions (the ability to respond and to stimulate) in mixed lymphocyte culture (MLC). This effect may have practical application in the prevention or reduction of transfusion-induced alloimmunization against HLA class I antigens. To study this, platelet concentrates (PCs) were obtained with a cell separator, suspended in autologous plasma in a final volume of 400 mL, and transferred into a large (22 X 30 cm) cell culture bag. This plastic showed a good transmittance of UV-B rays at 310 nm (54%). PCs were placed between two quartz plates (surface of irradiation = 25 X 37 cm), and the two sides were irradiated simultaneously. Energy delivered to the surface of the plastic bag was automatically monitored. The ability to respond (in MLC and to phytohemagglutinin) and to stimulate allogeneic lymphocytes was completely abolished with energy of 0.75 J per cm2 (irradiation time less than 3 min). The temperature increase during irradiation was negligible. Platelet aggregation (collagen, adrenalin, ADP, arachidonic acid, ristocetin) was not impaired if UV-B energy was below 3 J per cm2. Recovery and survival of autologous 111In-labeled platelets were studied in four volunteers; no differences were found between UV-B-treated (1.5 J/cm2) platelets and untreated platelets. These results show that a large-scale clinical trial using UV-B-irradiated PCs to prevent HLA alloimmunization is feasible.

  6. [Effects of lysine clonixinate on platelet function. Comparison with other non-steroidal anti-inflammatory agents].

    Science.gov (United States)

    Kramer, E H; Sassetti, B; Kaminker, A J; De Los Santos, A R; Martí, M L; Di Girolamo, G

    2001-01-01

    One of the mechanisms of action of non steroid antiinflammatory drugs (NSAIDs) consists of inhibition of prostaglandin synthesis. This explains many of the pharmacological effects and adverse events observed in medical practice. Administration of NSAIDs to patients with hemostatic disorders or perioperative conditions entails the risk of bleeding due to inhibition of platelet function. This study deals with platelet changes induced by lysine clonixinate vs diclofenac, ibuprofen and aspirin in classical tests such as platelet count, platelet factor 3 (PF3) activity and platelet aggregation with various inductors and more recent procedures such as P-selectin measurement by flow cytometry. Unlike control drugs, lysine clonixinate did not induce changes in platelet count or function when administered to healthy volunteers at the commonly used therapeutic doses. PMID:11474878

  7. Platelets actively sequester angiogenesis regulators

    OpenAIRE

    Lakka Klement, Giannoula; Yip, Tai-Tung; Cassiola, Flavia; Kikuchi, Lena; Cervi, David; Podust, Vladimir; Italiano, Joseph E.; Wheatley, Erin; Abou-Slaybi, Abdo; Bender, Elise; Almog, Nava; Kieran, Mark W.; Folkman, Judah

    2009-01-01

    Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non–tumor...

  8. The effects of ropivacaine hydrochloride on platelet function: an assessment using the platelet function analyser (PFA-100).

    LENUS (Irish Health Repository)

    Porter, J

    2012-02-03

    Amide local anaesthetics impair blood clotting in a concentration-dependent manner by inhibition of platelet function and enhanced fibrinolysis. We hypothesised that the presence of ropivacaine in the epidural space could decrease the efficacy of an epidural blood patch, as this technique requires that the injected blood can clot in order to be effective. Ropivacaine is an aminoamide local anaesthetic used increasingly for epidural analgesia during labour. The concentration of local anaesthetic in blood achieved in the epidural space during the performance of an epidural blood patch is likely to be the greatest which occurs (intentionally) in any clinical setting. This study was undertaken to investigate whether concentrations of ropivacaine in blood, which could occur: (i) clinically in the epidural space and (ii) in plasma during an epidural infusion of ropivacaine, alter platelet function. A platelet function analyser (Dade PFA-100, Miami) was employed to assess the effects of ropivacaine-treated blood on platelet function. The greater concentrations of ropivacaine studied (3.75 and 1.88 mg x ml(-1)), which correspond to those which could occur in the epidural space, produced significant inhibition of platelet aggregation. We conclude that the presence of ropivacaine in the epidural space may decrease the efficacy of an early or prophylactic epidural blood patch.

  9. Assessment of vascular-platelet hemostasis in patients with hemorrhagic forms of erysipelas

    Directory of Open Access Journals (Sweden)

    R. I. Ratnikova

    2012-01-01

    Full Text Available The article presents the results of the research of vascular-platelet hemostasis in dynamics with the patients with hemorrhagic forms of erysipelas. Found an increase platelet aggregation in the background of a decrease in the total number of the given clinical forms of the disease. The greatest changes were typical for bullosa hemorrhagic process in the study of collagen-induced aggregation. Also revealed the presence of endothelial dysfunction by increased activity of von Willebrand factor.

  10. 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.

  11. Impact of aspirin and clopidogrel interruption on platelet function in patients undergoing major vascular surgery.

    Directory of Open Access Journals (Sweden)

    Yannick Le Manach

    Full Text Available AIMS: To investigate functional platelet recovery after preoperative withdrawal of aspirin and clopidogrel and platelet function 5 days after treatment resumption. METHODS/RESULTS: We conducted an observational study, which prospectively included consecutive patients taking aspirin, taking clopidogrel, and untreated controls (15 patients in each group. The antiplatelet drugs were withdrawn five days before surgery (baseline and were reintroduced two days after surgery. Platelet function was evaluated by optical aggregation in the presence of collagen, arachidonic acid (aspirin and ADP (clopidogrel and by VASP assay (clopidogrel. Platelet-leukocyte complex (PLC level was quantified at each time-point. At baseline, platelet function was efficiently inhibited by aspirin and had recovered fully in most patients 5 days after drug withdrawal. PLC levels five days after aspirin reintroduction were similar to baseline (+4±10%; p = 0.16, in line with an effective platelet inhibition. Chronic clopidogrel treatment was associated with variable platelet inhibition and its withdrawal led to variable functional recovery. PLC levels were significantly increased five days after clopidogrel reintroduction (+10±15%; p = 0.02, compared to baseline. CONCLUSIONS: Aspirin withdrawal 5 days before high-bleeding-risk procedures was associated with functional platelet recovery, and its reintroduction two days after surgery restored antiplaletet efficacy five days later. This was not the case of clopidogrel, and further work is therefore needed to define its optimal perioperative management.

  12. Arsenic trioxide induces apoptosis in human platelets via C-Jun NH2-terminal kinase activation.

    Directory of Open Access Journals (Sweden)

    Yicun Wu

    Full Text Available Arsenic trioxide (ATO, one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL. However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm, up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation, and phosphotidylserine (PS exposure in platelets. ATO did not induce surface expression of P-selectin and PAC-1 binding, whereas, obviously reduced collagen, ADP, and thrombin induced platelet aggregation. ATO dose-dependently induced c-Jun NH2-terminal kinase (JNK activation, and JNK specific inhibitor dicumarol obviously reduced ATO-induced ΔΨm depolarization in platelets. Clinical therapeutic dosage of ATO was intraperitoneally injected into C57 mice, and the numbers of circulating platelets were significantly reduced after five days of continuous injection. The data demonstrate that ATO induces caspase-dependent apoptosis via JNK activation in platelets. ATO does not incur platelet activation, whereas, it not only impairs platelet function but also reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia in patients treated with ATO.

  13. Arsenic trioxide induces apoptosis in human platelets via C-Jun NH2-terminal kinase activation.

    Science.gov (United States)

    Wu, Yicun; Dai, Jin; Zhang, Weilin; Yan, Rong; Zhang, Yiwen; Ruan, Changgeng; Dai, Kesheng

    2014-01-01

    Arsenic trioxide (ATO), one of the oldest drugs in both Western and traditional Chinese medicine, has become an effective anticancer drug, especially in the treatment of acute promyelocytic leukemia (APL). However, thrombocytopenia occurred in most of ATO-treated patients with APL or other malignant diseases, and the pathogenesis remains unclear. Here we show that ATO dose-dependently induces depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax and down-regulation of Bcl-2 and Bcl-XL, caspase-3 activation, and phosphotidylserine (PS) exposure in platelets. ATO did not induce surface expression of P-selectin and PAC-1 binding, whereas, obviously reduced collagen, ADP, and thrombin induced platelet aggregation. ATO dose-dependently induced c-Jun NH2-terminal kinase (JNK) activation, and JNK specific inhibitor dicumarol obviously reduced ATO-induced ΔΨm depolarization in platelets. Clinical therapeutic dosage of ATO was intraperitoneally injected into C57 mice, and the numbers of circulating platelets were significantly reduced after five days of continuous injection. The data demonstrate that ATO induces caspase-dependent apoptosis via JNK activation in platelets. ATO does not incur platelet activation, whereas, it not only impairs platelet function but also reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia in patients treated with ATO. PMID:24466103

  14. Lectin-induced activation of platelets may require only limited phosphorylation of the 47K protein

    International Nuclear Information System (INIS)

    Wheat germ agglutinin (WGA) is an N-acetylglucosamine (Glc-NAc) specific lectin which can activate platelets. Like thrombin, stimulation of platelets by WGA is accompanied by enhanced phosphorylation of two polypeptides of M/sub r/ 47K and 20K. Addition of GlcNAc at different time intervals arrested that aggregation of platelets by WGA and paralleled the modification of phosphorylation of the 47K polypeptide. So, the phosphorylation of the 47K polypeptide may regulate the WGA-receptor mediated stimulation of platelets. However, the ratio of phosphoserine to phosphothreonine in the 47K protein was markedly different in WGA-activated than thrombin-stimulated platelets. Thus, the molecular mechanism of action of thrombin and WGA could be different. To explore this idea, 32P/sub i/-labeled platelets were stimulated with WGA and the activation arrested with N-acetyl-glucosamine at different times. Two-dimensional gel electrophoresis of total protein at 5s showed only two phosphorylated species of 47K protein. At 60s, maximally four phosphorylated species were noted. In contrast, with thrombin using the same technique, seven to nine phosphorylated components have been reported. These results suggest that the different activators of platelets may act by different mechanisms. In addition, activation of platelets may require only limited levels of phosphorylation of the 47K polypeptide

  15. Unique morphology and gradient arrangement of nacre's platelets in green mussel shells

    International Nuclear Information System (INIS)

    Nacre has long served as a classic model in biomineralization and the synthesis of biomimetic materials. However, the morphology and arrangement of its basic building blocks, the aragonite platelets, are still under hot debate. In this study, using a field emission scanning electron microscope (SEM), a high-resolution transmission electron microscope (HRTEM), and an X-ray diffractometer (XRD), we investigate the platelets at the edges and centers of green mussel shells. We find that 1) flat and curved platelets coexist in green mussel shells; 2) the immature platelets at the shell edge are aggregates of aragonite nanoparticles, whereas the immature ones at the shell center are single crystals; and 3) the morphology and thickness of the platelets exhibit a gradient arrangement. Based on these findings, we hypothesize that the gradient in the thickness and curvature of the platelets may probably result from the difference in growth rate between the edge and the center of the shell and from the gradient in compressive stress imposed by the closing of the shells by the adductor muscles or the withdrawal of the periostracum by the mantle. We expect that the presented results will shed new light on the formation mechanisms of natural composite materials. - Highlights: • Flat and curved platelets coexist in green mussel shells. • The immature platelets at the shell edge consist of aragonite nanoparticles. • The immature platelets at the shell center are single crystals. • The morphology and thickness of platelets exhibit a gradient arrangement. • The gradient arrangement of platelets may result from the stress gradient

  16. Unique morphology and gradient arrangement of nacre's platelets in green mussel shells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jun; Zhang, Gangsheng, E-mail: zhanggs@gxu.edu.cn

    2015-07-01

    Nacre has long served as a classic model in biomineralization and the synthesis of biomimetic materials. However, the morphology and arrangement of its basic building blocks, the aragonite platelets, are still under hot debate. In this study, using a field emission scanning electron microscope (SEM), a high-resolution transmission electron microscope (HRTEM), and an X-ray diffractometer (XRD), we investigate the platelets at the edges and centers of green mussel shells. We find that 1) flat and curved platelets coexist in green mussel shells; 2) the immature platelets at the shell edge are aggregates of aragonite nanoparticles, whereas the immature ones at the shell center are single crystals; and 3) the morphology and thickness of the platelets exhibit a gradient arrangement. Based on these findings, we hypothesize that the gradient in the thickness and curvature of the platelets may probably result from the difference in growth rate between the edge and the center of the shell and from the gradient in compressive stress imposed by the closing of the shells by the adductor muscles or the withdrawal of the periostracum by the mantle. We expect that the presented results will shed new light on the formation mechanisms of natural composite materials. - Highlights: • Flat and curved platelets coexist in green mussel shells. • The immature platelets at the shell edge consist of aragonite nanoparticles. • The immature platelets at the shell center are single crystals. • The morphology and thickness of platelets exhibit a gradient arrangement. • The gradient arrangement of platelets may result from the stress gradient.

  17. Human platelets express CAR with localization at the sites of intercellular interaction

    Directory of Open Access Journals (Sweden)

    Othman Maha

    2011-09-01

    Full Text Available Abstract Adenovirus has a wide tissue tropism. The virus attaches to the surface of cells via the fiber protein knob binding to the Coxsackie and Adenovirus receptor known as CAR. Virus entry inside cells is facilitated by integrins αVβ3 and αVβ5. Mice platelets are shown to be the predominant Ad binding blood cell type and the virus is documented inside platelets. CAR was identified on human platelets in one study yet contradicted in another. The presence of CAR appears to be the most reasonable initial step for virus entry into platelets and is a key to the understanding of platelet adenovirus interaction. This study aimed to re investigate the presence of CAR on human platelets. Platelets were tested by indirect immune-fluorescence using rabbit H-300 polyclonal anti-CAR antibody and goat anti-rabbit IgG F(ab'2 Texas Red antibodies, alongside with CAR positive and negative controls. Platelets were found to express CAR on their surface and in contrast to the previous study only 3.5 ± 1.9% of the tested platelets did express CAR. In addition, CAR was seen within intracellular aggregates localized at the sites of cell-cell contacts indicating that CAR expression might be upregulated in response to platelet stimulation. We confirm the presence of CAR on human platelets, we provide explanation to some of the discrepancies in this regards and we add that this receptor is localized at the sites of intercellular interaction.

  18. Involvement of nuclear factor {kappa}B in platelet CD40 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Hachem, Ahmed [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Yacoub, Daniel [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Zaid, Younes [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Mourad, Walid [Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada); Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1 (Canada); Merhi, Yahye, E-mail: yahye.merhi@icm-mhi.org [Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada H1T 1C8 (Canada); Universite de Montreal, Department of Medicine, 2900 boul. Edouard-Montpetit, Montreal, Quebec, Canada H3T 1J4 (Canada)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Given that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo

  19. The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations

    DEFF Research Database (Denmark)

    Thastrup, Ole; Linnebjerg, H; Bjerrum, P J;

    1987-01-01

    We have studied the activation of human blood platelets by the inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin. The effect of thapsigargin was compared with other common agonists (calcium ionophore A23187, phorbol ester TPA and thrombin). Platelet aggregation, serotonin release...

  20. Platelet-activating factor (PAF)-dependent biochemical, morphologic, and physiologic responses of human platelets: Demonstration of translocation of protein kinase C associated with protein phosphorylation

    International Nuclear Information System (INIS)

    Platelet-activating factor (PAF) is a potent stimulus for platelet aggregation and secretion. PAF has been shown to stimulate the phosphatidylinositol (PI) pathway in platelets, which implies that PAF should activate protein kinase C. In this study, measurements of PI metabolites, the elevation of intracellular free calcium concentration, (Ca2+)i, the activation of protein kinase C, and the phosphorylation of platelet proteins (using a two-dimensional gel electrophoretic technique) were performed before and after the addition of 10(-8) M PAF to human platelets. These findings were correlated with morphologic changes in the platelets as determined by immunoelectron microscopic studies on the cytoskeleton and by X-ray analysis of dense bodies. The results show that PAF stimulates the production of PI metabolites and causes an increase in the membrane-associated activity of protein kinase C. These changes are accompanied by a rise in the (Ca2+)i and protein phosphorylation. The increase in protein kinase C activity reaches a maximum at approximately 60 s, a time frame that is consistent with the protein phosphorylation and the subsequent morphologic and secretory events. X-ray analysis revealed two types of dense bodies containing various amounts of calcium which appeared to be released sequentially after PAF activation. These results suggest that the protein phosphorylation that controls the physiologic events resulting from PAF activation of human platelets is catalyzed by protein kinase C

  1. Role of 5-hydroxytryptamine in platelet thrombus formation and mechanisms of inhibition of thrombus formation by 5-hydroxytryptamine2A antagonists in rabbits.

    Science.gov (United States)

    Takano, S

    1995-01-01

    The role of 5-hydroxytryptamine (5-HT) in platelet thrombus formation and in the mechanisms of inhibition of thrombus formation by 5-HT2A antagonists was investigated using a turbidimetric method. Collagen-induced platelet aggregation occurred simultaneously with a release of 5-HT from the platelets. The supernatant of collagen-aggregated platelets induced a further aggregation volume-dependently. This supernatant-induced aggregation was inhibited by either 5-HT2A antagonists or adenosine-diphosphate (ADP) scavenging. 5-Hydroxytryptamine and a small amount of the supernatant shifted the dose-response curves of collagen to the left. The aggregation velocity and the onset of aggregation by collagen were significantly increased by the supernatant, but not by 5-HT. The 5-HT2A antagonists, ketanserin and MCI-9042, returned the dose-response curves of the maximum aggregation and of the aggregation velocity of collagen, which were already amplified by the supernatant, to the original values. The onset of aggregation was delayed by the antagonists, but was not completely returned to the original points. There were distinct differences between the effects of endogenous 5-HT, derived from platelets which were stimulated by collagen, and those of exogenous 5-HT on both extensive platelet activation and amplification of the collagen-induced aggregation. These findings suggest that endogenous 5-HT activates platelets in synergism with ADP. The 5-HT2A antagonists used, block the synergism via 5-HT2A receptors and lead to inhibition of a positive feedback loop of thrombus formation. PMID:8836449

  2. Genomics of platelet disorders.

    Science.gov (United States)

    Westbury, S K; Mumford, A D

    2016-07-01

    Genetic diagnosis in families with inherited platelet disorders (IPD) is not performed widely because of the genetic heterogeneity of this group of disorders and because in most cases, it is not possible to select single candidate genes for analysis using clinical and laboratory phenotypes. Next-generation sequencing (NGS) technology has revolutionized the scale and cost-effectiveness of genetic testing, and has emerged as a valuable tool for IPD. This review examines the potential utility of NGS as a diagnostic tool to streamline detection of causal variants in known IPD genes and as a vehicle for new gene discovery. PMID:27405671

  3. Human platelet calmodulin-binding proteins: Ca/sup 2 +/-dependent proteolysis upon platelet activation

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, R.W.; Tallant, E.A.; McManus, M.C.

    1986-05-01

    Calmodulin (CaM)-binding proteins have been identified in human platelets using Western blotting techniques and /sup 125/I-CaM. Ten distinct proteins with molecular weights of 245, 225K, 175K, 150K, 90K, 82K(2), 60K and 41K(2) bound /sup 125/I-CaM in a Ca/sup 2 +/-dependent manner; the binding was blocked by both trifluoperazine and nonradiolabeled CaM. The 225K and 90K proteins were labeled by antisera against myosin light chain kinase (MLCK); the 60K and one of the 82K proteins were identified as the CaM-dependent phosphatase and caldesmon. The remaining proteins have not yet been identified. Most of the CaM-binding proteins were degraded upon addition of Ca/sup 2 +/ to a platelet homogenate; the degradation could be blocked by either EGTA, leupeptin or N-ethyl-maleimide which suggests that it was due to a Ca/sup 2 +/-dependent protease. Activation of intact platelets by thrombin, ADP, collagen and the Ca/sup 2 +/-ionophores A23187 and ionomycin under conditions which promote platelet aggregation (i.e. stirring with extracellular Ca/sup 2 +/) also resulted in limited proteolysis of CaM-binding proteins including those labeled with anti-MLCK and the phosphatase. Many Ca/sup 2 +//CaM-regulated enzymes have been shown to be irreversibly activated in vitro by limited proteolysis. Their data indicates that limited proteolysis also occurs in vivo; under certain conditions proteolysis may be an important physiological mechanism for irreversibly activating Ca/sup 2 +//CaM-regulated enzymes.

  4. The role of oxidized albumin in blood cell aggregation disturbance in burn disease

    OpenAIRE

    Levin, Grigory Ya; Egorihina, Marpha N

    2013-01-01

    The burn disease is found to be accompanied by increasing of the level of oxidized proteins of blood serum. We studied the influence of albumin oxidation rate on aggregation of platelets and erythrocytes, disaggregation of erythrocytes. The changes of blood cells aggregation associated with oxidation rate of albumin were found. Possible mechanisms of these effects are discussed.

  5. Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans.

    Directory of Open Access Journals (Sweden)

    Lea M Beaulieu

    Full Text Available Diverse and multi-factorial processes contribute to the progression of cardiovascular disease. These processes affect cells involved in the development of this disease in varying ways, ultimately leading to atherothrombosis. The goal of our study was to compare the differential effects of specific stimuli--two bacterial infections and a Western diet--on platelet responses in ApoE-/- mice, specifically examining inflammatory function and gene expression. Results from murine studies were verified using platelets from participants of the Framingham Heart Study (FHS; n = 1819 participants.Blood and spleen samples were collected at weeks 1 and 9 from ApoE-/- mice infected with Porphyromonas gingivalis or Chlamydia pneumoniae and from mice fed a Western diet for 9 weeks. Transcripts based on data from a Western diet in ApoE-/- mice were measured in platelet samples from FHS using high throughput qRT-PCR.At week 1, both bacterial infections increased circulating platelet-neutrophil aggregates. At week 9, these cells individually localized to the spleen, while Western diet resulted in increased platelet-neutrophil aggregates in the spleen only. Microarray analysis of platelet RNA from infected or Western diet-fed mice at week 1 and 9 showed differential profiles. Genes, such as Serpina1a, Ttr, Fgg, Rpl21, and Alb, were uniquely affected by infection and diet. Results were reinforced in platelets obtained from participants of the FHS.Using both human studies and animal models, results demonstrate that variable sources of inflammatory stimuli have the ability to influence the platelet phenotype in distinct ways, indicative of the diverse function of platelets in thrombosis, hemostasis, and immunity.

  6. CV-6209, a highly potent antagonist of platelet activating factor in vitro and in vivo.

    Science.gov (United States)

    Terashita, Z; Imura, Y; Takatani, M; Tsushima, S; Nishikawa, K

    1987-07-01

    2-[N-acetyl-N-(2-methoxy-3-octadecylcarbamoyloxypropoxycarbonyl) aminomethyl]-1-ethylpyridinium chloride (CV-6209) inhibited aggregation of rabbit and human platelets induced by platelet activating factor (PAF) with the IC50 values of 7.5 X 10(-8) and 1.7 X 10(-7) M, respectively, and had little effects on the aggregation induced by arachidonic acid, ADP and collagen. The inhibitory effect of CV-6209 on the PAF-induced rabbit platelet aggregation was 104, 9, 8 and 3 times more potent than the PAF antagonists CV-3988, ONO-6240, Ginkgolide B and etizolam, respectively. CV-6209 inhibited [3H]serotonin release from rabbit platelets stimulated with PAF (3 X 10(-8) M) with a similar potency as the inhibition on the platelet aggregation. CV-6209 inhibited PAF (0.3 microgram/kg i.v.)-induced hypotension in rats (ED50, 0.009 mg/kg i.v.) with no effect on the hypotension induced by arachidonic acid, histamine, bradykinin and isoproterenol. CV-6209 (1 mg/kg) inhibited slightly the acetylcholine-induced hypotension. In rats, post-treatment with CV-6209 reversed the PAF (1 microgram/kg i.v.)-induced hypotension rapidly (ED50, 0.0046 mg/kg i.v.); CV-6209 was 74, 20, 185 and over 2100 times more potent than CV-3988, ONO-6240, Ginkgolide B and etizolam, respectively. Thus, the relative potency of the anti-PAF action of PAF analog (CV-6209, CV-3988 and ONO-6240) differed little between the inhibition of PAF-induced platelet aggregation and the reversal of PAF-induced hypotension, but that of nonPAF analogs (Ginkgolide B and etizolam) differed greatly with these assay systems, when standardized with CV-6209.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3612533

  7. The correlation between clinical neurologic impairment in acute cerebral thrombosis patients and the status of platelet and fibrinogen%急性脑梗死患者临床神经功能缺损程度与血小板及纤维蛋白原状态的相关性

    Institute of Scientific and Technical Information of China (English)

    李秀珍; 殷宇刚; 杨静; 万太玉; 韩恩吉

    2002-01-01

    @@ Large numbers of researches indicate that platelets (PLT) and fibrinogen (FIB)play important roles in the pathogenesis and progress of cerebral thrombosis. In the present study,PLT,platelet mean volume (MPV),platelet aggregation ratio (PtAgt) and FIB concentration were observed,and the pathogenesis and the progress were discussed.

  8. The mojastin mutant Moj-DM induces apoptosis of the human melanoma SK-Mel-28, but not the mutant Moj-NN nor the non-mutated recombinant Moj-WN

    OpenAIRE

    Seoane, Agustin I.; Tran, Victoria L.; Sanchez, Elda E.; White, Stephanie A.; Choi, Jason L.; Gaytán, Brandon; Chavez, Natalie; Reyes, Steven R.; Ramos, Carla J.; Luan H. Tran; Lucena, Sara E.; Sugarek, Maria; Perez, John C.; Mandal, Stephanie A.; Ghorab, Shervin

    2010-01-01

    In this study, three recombinant mojastin peptides (Moj-WN, Moj-NN, and Moj-DM) were produced and compared functionally. Recombinant Moj peptides were purified as GST-fusions. GST-Moj-WN and GST-Moj-NN inhibited ADP-induced platelet aggregation in platelet rich plasma. The GST-Moj-WN had an IC50 of 160 nM, while the GST-Moj-NN had an IC50 of 493 nM. The GST-Moj-DM did not inhibit platelet aggregation. All three GST-Moj peptides inhibited SK-Mel-28 cell adhesion to fibronectin. The GST-Moj-WN ...

  9. Role of platelets in inflammation

    Directory of Open Access Journals (Sweden)

    Kadir Serkan Yalçın

    2012-09-01

    Full Text Available Inflammation, which is extremely useful process for humanbody is the response of living vascular tissues topathological phenomena that removes the pathogens andinitiates the healing procedure. Microorganisms, physicaltrauma, chemical, mechanical, irradiation, or thermal injury,ischemia and immune reactions are most commoncauses of this exceptionally important event for humanbody. Platelets are non-nucleated cells in blood that producedin bone marrow as derived from megakaryocytes.Apart from stop bleeding and achieving hemostasis thereare incredibly important roles of platelets in inflammation.Platelets contain important mediators for inflammationlike neutrophils or macrophages and can alter the courseof mechanism. In this article changing platelet function ininflammation and the effect of these functions to the processof inflammation will be discussed.Key words: Platelet, inflammation, cytokines

  10. 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

  11. Aggregation of Calcium Silicate Hydrate Nanoplatelets.

    Science.gov (United States)

    Delhorme, Maxime; Labbez, Christophe; Turesson, Martin; Lesniewska, Eric; Woodward, Cliff E; Jönsson, Bo

    2016-03-01

    We study the aggregation of calcium silicate hydrate nanoplatelets on a surface by means of Monte Carlo and molecular dynamics simulations at thermodynamic equilibrium. Calcium silicate hydrate (C-S-H) is the main component formed in cement and is responsible for the strength of the material. The hydrate is formed in early cement paste and grows to form platelets on the nanoscale, which aggregate either on dissolving cement particles or on auxiliary particles. The general result is that the experimentally observed variations in these dynamic processes generically called growth can be rationalized from interaction free energies, that is, from pure thermodynamic arguments. We further show that the surface charge density of the particles determines the aggregate structures formed by C-S-H and thus their growth modes. PMID:26859614

  12. Platelet Component of Hemostasis System and the Content of Homocysteine in Blood Serum in Coxarthrosis

    OpenAIRE

    Fedoseeva I.А.; Ezhov I.Y.; Tcharykova I.N.

    2011-01-01

    The aim of the investigation is to study the content of homocysteine in blood serum and the analysis of thrombocyte aggregation activity in patients suffering from degenerative-dystrophic diseases of coxofemoral joint (coxarthrosis). Materials and Methods. There have been examined 155 patients with coxarthrosis and 45 healthy men and women aged 45—65 years old. The platelet aggregation ability has been studied using adenosine diphosphate (ADP) in small doses (1.25 mkg/ml) and collagen (2....

  13. Effects of copper-aspirin complex on platelet-neutrophil interactions

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiang SHEN; Peng CHEN; Ling LI; Peng CHEN; Wei-ping LIU

    2004-01-01

    AIM: To investigate the effects of copper-aspirin complex on rat thrombosis and the interaction between platelets and neutrophils. METHODS: The model of electrically stimulated carotid artery thrombosis in Sprague Dawley rats was used; the effects of copper-aspirin complex on rat platelet-neutrophil adhesion and platelet aggregation stimulated by activated neutrophils were observed by rosette assay and Born's method, respectively. RESULTS:Intragastric copper-aspirin complex (5, 7, and 10 mg/kg) dose-dependently prolonged the occlusion time; it significantly decreased the rosette number formed between thrombin-activated platelets and neutrophils; the 50 % of inhibitory concentration (IC50) was (54.6±4.3) μmol/L. Copper-aspirin complex markedly inhibited rat platelet aggregation induced by either cell free supernatant of activated neutrophils or by activated neutrophil suspension.The values of IC50 were (224.5±16.2) μmol/L and (820.5±21.4) μmol/L, whereas aspirin had no influence.CONCLUSION: Copper-aspirin complex inhibited platelet-neutrophil interactions through a different property from aspirin and resulted in a more potent antithrombotic activity.

  14. Impact of anemia on platelet response to clopidogrel in patients undergoing percutaneous coronary stenting.

    Science.gov (United States)

    Toma, Catalin; Zahr, Firas; Moguilanski, Diego; Grate, Sheree; Semaan, Roy W; Lemieux, Nicole; Lee, Joon S; Cortese-Hassett, Andrea; Mulukutla, Suresh; Rao, Sunil V; Marroquin, Oscar C

    2012-04-15

    High residual platelet reactivity (HRPR) on clopidogrel is a predictor of recurrent ischemic events in patients undergoing percutaneous coronary interventions (PCI). Significant intraindividual variability in platelet aggregation on repeat testing has been reported. To understand factors contributing to the variability in platelet aggregation testing, we examined clinical and laboratory elements linked to HRPR in 255 consecutive patients tested ≥12 hours after PCI using light transmission aggregometry (LTA) in response to adenosine diphosphate 5 μmol/L and VerifyNow P2Y12 assay (VNP2Y12; Accumetrics). HRPR was defined as >46% residual aggregation for LTA and >236 P2Y12 response units (PRUs) for VNP2Y12. On multivariate analysis the only variable independently associated with HRPR with both LTA and VNP2Y12 was laboratory-defined anemia. Prevalences of HRPR by LTA were 34.3% in anemic patients, 15.6% in patients with normal hemoglobin levels, and 59.8% versus 25.9% by VNP2Y12 (p <0.005 for the 2 comparisons). In a subgroup of 50 patients, testing was done before and after the clopidogrel loading dose. At baseline there were no differences in platelet aggregation with either assay; however, absolute decrease in reactivity after the clopidogrel load was significantly less in anemic patients compared to patients with normal hemoglobin (change in residual aggregation by LTA 15.8 ± 5.8% vs 28.8 ± 3.2%, p <0.05; change in PRU by VNP2Y12 56.5 ± 35.5 vs 145.0 ± 14.2 PRUs, p <0.05, respectively). In conclusion, anemia is an important contributor to apparent HRPR on clopidogrel and may explain some of the intraindividual variability of platelet aggregation testing. PMID:22277895

  15. Platelet function during cardiopulmonary bypass using multiple electrode aggregometry: comparison of centrifugal and roller pumps.

    Science.gov (United States)

    Kehara, Hiromu; Takano, Tamaki; Ohashi, Noburo; Terasaki, Takamitsu; Amano, Jun

    2014-11-01

    Blood trauma may be lower with centrifugal pumps (CPs) than with roller pumps (RPs) during cardiopulmonary bypass (CPB), because, unlike RPs, CPs do not compress the tubing, and shear stress is considered lower in CPs than in RPs. However, relative platelet function remains unclear. Using multiple electrode aggregometry (MEA), we compared platelet function with CP and RP. Ten swine underwent CPB for 3 h, with five weaned off using CP and five using RP. Platelet function was measured using MEA, as were hemoglobin concentration and platelet count, before sternotomy, after heparin infusion, 30 min and 3 h after starting CPB, after protamine infusion, and 60 min after stopping CPB. Platelet activation was initiated with adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating protein 6 (TRAP). Fibrinogen, platelet factor 4 (PF4), and β-thromboglobin (β-TG) concentrations were measured before sternotomy and 60 min after stopping CPB. In the CP group and using ADP, aggregation was significantly reduced 30 min (P = 0.019) and 3 h (P = 0.027) after starting CPB, recovering to baseline 60 min after CPB was stopped. In the RP group, aggregation was significantly decreased 30 min (P = 0.007) and 3 h (P = 0.003) after starting CPB and after protamine administration (P = 0.028). With AA, aggregation significantly decreased 30 min after starting CPB in both the CP (P = 0.012) and RP (P = 0.016) groups, slightly increasing 3 h after starting CPB and after protamine infusion, and recovering to baseline 60 min after CPB cessation. With TRAP, aggregation in the CP and RP groups decreased 30 min after starting the pump, although changes were not significant; aggregation gradually recovered after 3 h and returned to baseline 60 min after the pumps were stopped. There were no significant differences at all sampling points of MEA. In both groups, fibrinogen, PF4, and β-TG concentrations were similar 60 min after pump cessation and before sternotomy

  16. Radioimmune assay of human platelet prostaglandin synthetase

    International Nuclear Information System (INIS)

    Normal platelet function depends, in part, on platelet PG synthesis. PG synthetase (cyclo-oxygenase) catalyzes the first step in PG synthesis, the formation of PGH2 from arachidonic acid. Inhibition of the enzyme by ASA results in an abnormality in the platelet release reaction. Patients with pparent congenital abnormalities in the enzyme have been described, and the effects have been referred to as ''aspirin-like'' defects of the platelet function. These patients lack platelet PG synthetase activity, but the actual content of PG synthetase protein in these individuals' platelets is unknown. Therefore an RIA for human platelet PG synthetase would provide new information, useful in assessing the aspirin-like defects of platelet function. An RIA for human platelet PG synthetase is described. The assay utilizes a rabbit antibody directed against the enzyme and [125I]-labelled sheep PG synthetase as antigen. The human platelet enzyme is assayed by its ability to inhibit precipitation of the [125I]antigen. The assay is sensitive to 1 ng of enzyme. By the immune assay, human platelets contain approximately 1200 ng of PG synethetase protein per 1.5 mg of platelet protein (approximately 109 platelets). This content corresponds to 10,000 enzyme molecules per platelet. The assay provides a rapid and convenient assay for the human platelet enzyme, and it can be applied to the assessment of patients with apparent platelet PG synthetase (cyclo-oxygenase) deficiency

  17. Freezing of Apheresis Platelet Concentrates in 6% Dimethyl Sulfoxide: The First Preliminary Study in Turkey

    Directory of Open Access Journals (Sweden)

    Soner Yılmaz

    2016-03-01

    Full Text Available Objective: Transfusion of platelet suspensions is an essential part of patient care for certain clinical indications. In this pioneering study in Turkey, we aimed to assess the in vitro hemostatic functions of platelets after cryopreservation. Materials and Methods: Seven units of platelet concentrates were obtained by apheresis. Each apheresis platelet concentrate (APC was divided into 2 equal volumes and frozen with 6% dimethyl sulfoxide (DMSO. The 14 frozen units of APCs were kept at -80 °C for 1 day. APCs were thawed at 37 °C and diluted either with autologous plasma or 0.9% NaCl. The volume and residual numbers of leukocytes and platelets were tested in both before-freezing and post-thawing periods. Aggregation and thrombin generation tests were used to analyze the in vitro hemostatic functions of platelets. Flow-cytometric analysis was used to assess the presence of frozen treated platelets and their viability. Results: The residual number of leukocytes in both dilution groups was <1x106. The mean platelet recovery rate in the plasma-diluted group (88.1±9.5% was higher than that in the 0.9% NaCl-diluted group (63±10%. These results were compatible with the European Directorate for the Quality of Medicines quality criteria. Expectedly, there was no aggregation response to platelet aggregation test. The mean thrombin generation potential of postthaw APCs was higher in the plasma-diluted group (2411 nmol/L per minute when compared to both the 0.9% NaCl-diluted group (1913 nmol/L per minute and the before-freezing period (1681 nmol/L per minute. The flowcytometric analysis results for the viability of APCs after cryopreservation were 94.9% and 96.6% in the plasma and 0.9% NaCl groups, respectively. Conclusion: Cryopreservation of platelets with 6% DMSO and storage at -80 °C increases their shelf life from 7 days to 2 years. Besides the increase in hemostatic functions of platelets, the cryopreservation process also does not affect their

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

    Directory of Open Access Journals (Sweden)

    Wei Li

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

  19. Platelet Function During Hypothermia in Experimental Mock Circulation.

    Science.gov (United States)

    Van Poucke, Sven; Stevens, Kris; Kicken, Cécile; Simons, Antoine; Marcus, Abraham; Lancé, Marcus

    2016-03-01

    Alterations in platelet function are a common finding in surgical procedures involving cardiopulmonary bypass and hypothermia. Although the combined impact of hypothermia and artificial circulation on platelets has been studied before, the ultimate strategy to safely minimize the risk for bleeding and thrombosis is yet unknown. The aim of this study was to evaluate the use of a mock circulation loop to study the impact of hypothermia for platelet-related hemostatic changes. Venous blood was collected from healthy adult humans (n = 3). Closed mock circulation loops were assembled, each consisting of a centrifugal pump, an oxygenator with integrated heat exchanger, and a hardshell venous reservoir. The experiment started with the mock circulation temperature set at 37°C (T0 [0 h]). Cooling was then initiated at T1 (+2 h), where temperature was adjusted from 37°C to 32°C. Hypothermia was maintained from T2 (+4 h) to T3 (+28 h). From that point in time, rewarming from 32°C to 37°C was initiated with similar speed as cooling. From time point T4 (+30 h), normothermia (37°C) was maintained until the experiment ended at T5 (+32 h). Blood samples were analyzed in standard hematological tests: light transmission aggregometry (LTA) (arachidonic acid [AA], adenosine diphosphate [ADP], collagen [COL], thrombin-receptor-activating-peptide-14 [TRAP]), multiple electrode aggregometry (MEA) (AA, ADP, COL, TRAP), and rotational thromboelastometry (ROTEM) (EXTEM, FIBTEM, PLTEM). Hemoglobin, hematocrit, and platelet count decrease more substantially during temperature drop (37-32°C) than during hypothermia maintenance. Hb and Hct continue to follow this trend during active rewarming (32-37°C). PC increase from the moment active rewarming was initiated. None of the values return to the initial values. LTA values demonstrate a similar decrease in aggregation after stimulation with the platelet agonists between the start of the mock circulation and the start of

  20. Aggregation of Scale Efficiency

    OpenAIRE

    Valentin Zelenyuk

    2012-01-01

    In this article we extend the aggregation theory in efficiency and productivity analysis by deriving solutions to the problem of aggregation of individual scale efficiency measures, primal and dual, into aggregate primal and dual scale efficiency measures of a group. The new aggregation result is coherent with aggregation framework and solutions for the other related efficiency measures that already exist in the literature.

  1. Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin clot lysis time in patients with mild hypertension

    DEFF Research Database (Denmark)

    Fonitz, Gitte (Gleerup); Petersen, J R; Mehlsen, J; Winther, Kaj

    1996-01-01

    Thirteen patients with mild hypertension (untreated diastolic blood pressure of 95 to 114 mmHg) received, in random order, three successive treatments of four weeks with placebo, spirapril (6 mg daily), or hydrochlorothiazide (HCT2) (24 mg daily). At the end of each treatment, blood samples for...... assessment of platelet aggregation and platelet release of platelet factor 4 (PF4) and for assessment of fibrinolysis, estimated by tissue plasminogen activator (t-PA), plasminogen activator inhibitor-type 1 (PAI-1), and euglobulin clot lysis time (ECLT), were taken, first at rest, then immediately after...... five to ten minutes of vigorous exercise, and finally after the subsequent hour of recovery rest. Platelet aggregation induced in vitro by adrenaline significantly decreased during treatment with HCT2, the threshold rising to 10 microM as compared with 1.0 with placebo (P <0.05) at rest, and the...

  2. Chloride channels of platelets%血小板氯通道

    Institute of Scientific and Technical Information of China (English)

    陈晓琳; 尹松梅

    2004-01-01

    Chloride channels distribute widely in the body, and participate in many physiological actions and regulatory processes. Based on their physiological roles and molecular structures, six kinds of chloride channels have been identified: (1) The chloride channels family; (2) Cystic fibrosis transmembrane conductance regulator; (3) Swelling-activated chloride channels; (4) Calcium-activated chloride channels; (5) The p64 (CLIC) gene family; (6) γ-aminobutyric acid and glycine receptors. The chloride channels do exist in platelets, and their appearances are dependent on the presence of intracellular calcium. Blocking agents of chloride channels inhibit the thrombin-activated platelet aggregation and the elevation of the intracellular calcium concentration in a dose-dependent manner. It is suggested that chloride channels play a role in the activation of platelets. In addition, chloride channels act on both the cell volume regulation and the intracellular pH regulation in platelets.

  3. P2Y12 Platelet Receptors: Importance in Percutaneous Coronary Intervention

    International Nuclear Information System (INIS)

    Apart from their role in hemostasis and thrombosis, platelets are involved in many other biological processes such as wound healing and angiogenesis. Percutaneous coronary intervention is a highly thrombogenic procedure inducing platelets and monocytes activation through endothelial trauma and contact activation by intravascular devices. Platelet P2Y12 receptor activation by adenosine diphosphate facilitates non-ADP agonist-mediated platelet aggregation, dense granule secretion, procoagulant activity, and the phosphorylation of several intraplatelet proteins, making it an ideal drug target. However, not all compounds that target the P2Y12 receptor have similar efficacy and safety profiles. Despite targeting the same receptor, the unique pharmacologic properties of each of these P2Y12 receptor-directed compounds can lead to very different clinical effects

  4. P2Y{sub 12} Platelet Receptors: Importance in Percutaneous Coronary Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Falcão, Felipe Jose de Andrade, E-mail: felipejaf@gmail.com [Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP (Brazil); Carvalho, Leonardo; Chan, Mark [National University of Singapore - Yong Loo Lin School of Medicina (Singapore); Alves, Cláudia Maria Rodrigues; Carvalho, Antônio Carlos Camargo; Caixeta, Adriano Mendes [Universidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP (Brazil)

    2013-09-15

    Apart from their role in hemostasis and thrombosis, platelets are involved in many other biological processes such as wound healing and angiogenesis. Percutaneous coronary intervention is a highly thrombogenic procedure inducing platelets and monocytes activation through endothelial trauma and contact activation by intravascular devices. Platelet P2Y{sub 12} receptor activation by adenosine diphosphate facilitates non-ADP agonist-mediated platelet aggregation, dense granule secretion, procoagulant activity, and the phosphorylation of several intraplatelet proteins, making it an ideal drug target. However, not all compounds that target the P2Y{sub 12} receptor have similar efficacy and safety profiles. Despite targeting the same receptor, the unique pharmacologic properties of each of these P2Y{sub 12} receptor-directed compounds can lead to very different clinical effects.

  5. New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects

    Directory of Open Access Journals (Sweden)

    Derya Özsavcı

    2010-06-01

    Full Text Available Objective: We aimed to detect novel in vitro effects of clopidogrel on platelets by assessment of the following parameters: malondialdehyde, glutathione, nitrite, aggregation response, and expressions of P-selectin, fibrinogen, apolipoprotein A1, apolipoprotein B, and phosphatidylserine.Materials and Methods: Platelets were obtained from healthy (n: 9 and hyperlipidemic (n: 9 volunteers. Expressions of P-selectin, fibrinogen, apolipoproteins A1/B and phosphatidylserine with and without clopidogrel were assayed by flow cytometry. Malondialdehyde, glutathione, aggregation and nitrite levels were also assayed. Results: Without clopidogrel, the baseline values of platelet aggregation, malondialdehyde, and expressions of P-selectin, fibrinogen and phosphatidylserine were significantly higher, whereas nitrite and expression of apolipoproteins A1/B were significantly lower in hyperlipidemics than in the healthy group. In both groups, clopidogrel significantly reduced aggregation and expression of fibrinogen, but it elevated nitrite levels. Clopidogrel significantly decreased P-selectin and phosphatidylserine expression and malondialdehyde but increased expressions of apolipoproteins A1/B only in hyperlipidemics. Conclusion: It seems that clopidogrel has some new in vitro antiplatelet effects. The present study is a basic in vitro study to suggest new insights into the effects of clopidogrel on platelet functions.

  6. The effects of post coronary stenting triple antiplatelet therapies on platelet functions

    Institute of Scientific and Technical Information of China (English)

    韩雅玲

    2006-01-01

    Objective To explore the effects of triple antiplatelet therapy on platelet aggregation and activation in patients who underwent coronary stenting. Methods 120 inhospital coronary heart disease patients with coronary stenting were randomized into two groups receiving either triple antiplatelet drugs of aspirin and clopidogrel combined with cilostazol or dual antiplatelet drugs of aspirin and clopidogrel. On the first day after stenting cilostazol

  7. Platelet storage pool deficiency associated with inherited abnormalities of the inner ear in the mouse pigment mutants muted and mocha.

    Science.gov (United States)

    Swank, R T; Reddington, M; Howlett, O; Novak, E K

    1991-10-15

    Several inherited human syndromes have combined platelet, auditory, and/or pigment abnormalities. In the mouse the pallid pigment mutant has abnormalities of the otoliths of the inner ear together with a bleeding abnormality caused by platelet storage pool deficiency (SPD). To determine if this association is common, two other mouse pigment mutants, muted and mocha, which are known to have inner ear abnormalities, were examined for hematologic abnormalities. Both mutants had prolonged bleeding times accompanied by abnormalities of dense granules as determined by whole mount electron microscopy of platelets and by labeling platelets with mepacrine. When mutant platelets were treated with collagen, there was minimal secretion of adenosine triphosphate and aggregation was reduced. Lysosomal enzyme secretion in response to thrombin treatment was partially reduced in muted platelets and markedly reduced in mocha platelets. Similar reductions in constitutive lysosomal enzyme secretion from kidney proximal tubule cells were noted in the two mutants. These studies show that several mutations that cause pigment dilution and platelet SPD are associated with abnormalities of the inner ear. Also, these mutants, like previously described mouse pigment mutants, are models for human Hermansky-Pudlak syndrome and provide additional examples of single genes that simultaneously affect melanosomes, lysosomes, and platelet dense granules. PMID:1912584

  8. Involvement of platelet-tumor cell interaction in immune evasion. Potential role of podocalyxin-like protein 1

    Directory of Open Access Journals (Sweden)

    SusanaLarrucea

    2014-09-01

    Full Text Available Besides their essential role in hemostasis and thrombosis, platelets are involved in the onset of cancer metastasis by interacting with tumor cells. Platelets release secretory factors that promote tumor growth, angiogenesis, and metastasis. Furthermore, the formation of platelet-tumor cell aggregates in the bloodstream provides cancer cells with an immune escape mechanism by protecting circulating malignant cells from immune-mediated lysis by natural killer (NK cells. Platelet-tumor cell interaction is accomplished by specific adhesion molecules, including integrins, selectins, and their ligands. Podocalyxin-like protein 1 (PCLP1 is a selectin ligand protein which overexpression has been associated with several aggressive cancers. PCLP1 expression enhances cell adherence to platelets in an integrin-dependent process and through the interaction with P-selectin expressed on activated platelets. However, the involvement of PCLP1-induced tumor-platelet interaction in tumor immune evasion still remains unexplored. The identification of selectin ligands involved in the interaction of platelets with tumor cells may provide help for the development of effective therapies to restrain cancer cell dissemination. This article summarizes the current knowledge on molecules that participate in platelet-tumor cell interaction as well as discusses the potential role of PCLP1 as a molecule implicated in tumor immune evasion.

  9. Comparison of common platelet receptors between the chacma baboon (Papio ursinus) and human for use in pre-clinical human-targeted anti-platelet studies.

    Science.gov (United States)

    Janse van Rensburg, Walter J

    2016-06-01

    Anti-platelet agents play a central part in the treatment and prevention of acute thrombotic events. Discriminating animal models are needed for the development of novel agents. The chacma baboon has been extensively used as a model to evaluate anti-platelet agents. However, limited data exist to prove the translatability of this species to humans. We aimed to determine the suitability of the chacma baboon in preclinical human targeted GPIIb/IIIa, GPIbα and P2Y12 studies. Light-transmission platelet aggregometry (LTA), whole blood impedance aggregometry, receptor number quantification and genomic DNA sequencing were performed. Baboon ADP and arachidonic acid-induced LTA aggregation results differed significantly from human values, even at increased concentrations. LTA ristocetin-induced agglutination was comparable between species, but baboon platelets needed twice the concentration of ristocetin to elicit a similar response. Citrated baboon blood had significantly less aggregation than humans when evaluated with impedance aggregometry. However, hirudinised baboon whole blood gave similar aggregation as humans at the same agonist concentrations. GPIIb, GPIIIa and GPIbα numbers were significantly more on the baboon platelets. None of the amino acids deemed vital for receptor function, ligand binding or receptor inhibition, were radically different between the species. However, a conservative change in a calcium-binding region of GPIIb may render the baboon platelets more sensitive to calcium-binding agents. The chacma baboon may be used for the evaluation of human-targeted GPIIb/IIIa-, GPIbα- and P2Y12-inhibiting agents. However, the best anticoagulant, optimal agonist concentrations, increase in receptor number and sequence differences must be considered for any future studies. PMID:26559117

  10. A monoclonal antibody to the platelet membrane IIb-IIIa glycoprotein complex

    International Nuclear Information System (INIS)

    A hybridoma that secretes monoclonal mouse anti-platelet antibody has been produced by fusing spleen cells from immunized Balb/c mice with NS-1 myeloma cells using polyethylene glycol. Bulk production of the antibody was accomplished in vivo by injecting the cloned hybridoma cells intraperitoneally into pristane-primed mice. The antibody was purified from the ascitic fluid and characterised as belonging to the IgG1 sub-class by straphylococcal protein A-sepharose affinity chromatography. Purity was ascertained by SDS PAGE and isoelectric focusing. The antibody inhibited clot retraction of normal human blood and platelet aggregation induced by ADP, thrombin or epinephrine. Equilibrium binding studies revealed that the number of antibody molecules bound per platelet varied between 21 000 and 67 000 with an average of 42 000. Immunoprecipitation experiments with radioactively labelled platelets showed that the antibody bound the IIb-IIa glycoprotein complex. Platelets of patients with Glanzmann's thrombasthenia (a hereditary defect in which these glycoproteins are deficient) failed to bind the antibody. Immunofluorescent techniques showed that the antigen was present on megakaryocytes and platelets but not on the other cells from defibrinated peripheral blood. The antibody was also able to inhibit specifically the binding of radiolabelled human fibrinogen to ADP-stimulated platelets

  11. Cell surface thiol isomerases may explain the platelet-selective action of S-nitrosoglutathione.

    Science.gov (United States)

    Xiao, Fang; Gordge, Michael P

    2011-10-30

    S-nitrosoglutathione (GSNO) at low concentration inhibits platelet aggregation without causing vasodilation, suggesting platelet-selective nitric oxide delivery. The mechanism of this selectivity is unknown, but may involve cell surface thiol isomerases, in particular protein disulphide isomerase (csPDI) (EC 5.3.4.1). We have now compared csPDI expression and activity on platelets, endothelial cells and vascular smooth muscle cells, and the dependence on thiol reductase activity of these cell types for NO uptake from GSNO. csPDI expression was measured by flow cytometry and its reductase activity using the pseudosubstrate dieosin glutathione disulphide. This activity assay was adapted and validated for 96-well plate format. Flow cytometry revealed csPDI on all three cell types, but percentage positivity of expression was higher on platelets than on vascular cells. Consistent with this, thiol isomerase-related reductase activity was higher on platelets (Pionomycin) increased csPDI activity on both platelets and smooth muscle cells, but not on endothelium. Intracellular NO delivery from GSNO was greater in platelets than in vascular cells (Pselective actions of GSNO and help define its antithrombotic potential. PMID:21642008

  12. Platelet-tumor cell interaction with the subendothelial extracellular matrix: relationship to cancer metastasis

    International Nuclear Information System (INIS)

    Dissemination of neoplastic cells within the body involves invasion of blood vessels by tumor cells. This requires adhesion of blood-borne cells to the luminal surface of the vascular endothelium, invasion through the endothelial cell layer and local dissolution of the subendothelial basement membrane. The authors studied the interaction of platelets and tumor cells with cultured vascular endothelial cells and their secreted basement membrane-like extracellular matrix (ECM). Interaction of platelets with this ECM was associated with platelet activation, aggregation and degradation of heparan sulfate in the ECM by means of the platelet heparitinase. Biochemical and scanning electron microscopy (SEM) studies have demonstrated that platelets may detect even minor gaps between adjacent endothelial cells and degrade the ECM heparan sulfate. Platelets were also shown to recruit lymphoma cells into minor gaps in the vascular endothelium. It is suggested that the platelet heparitinase is involved in the impairment of the integrity of the vessel wall and thus play a role in tumor cell metastasis. (Auth.)

  13. Lactate is a possible mediator of the glucose effect on platelet inhibition.

    Science.gov (United States)

    Kobzar, Gennadi; Mardla, Vilja; Samel, Nigulas

    2014-01-01

    Abstract Glucose has been found to impair the inhibition of platelets with aspirin and alter the basal activity of nitric oxide synthase (NOS) in platelets. The aim of this work was to study the effects of glucose on the inhibitory pathways in activated platelets. A short-term incubation of glucose impaired the inhibition of platelet aggregation induced by agents activating an NOS-dependent pathway, such as l-arginine, adenosine and α-tocopherol. However, glucose had no effect on the inhibition induced by iloprost and BW245C, agents that activate the cyclic adenosine monophosphate (cAMP) signaling pathway. Potassium lactate attenuated the effects of the same inhibitors as glucose did. The inhibitors of glucose transport prevented the effect of glucose. Dichloroacetate, known to prevent the conversion of pyruvate to lactate and to decrease lactate in platelets, significantly attenuated the effect of glucose in platelets. The data support the suggestion that the effect of glucose on the inhibition of platelets by agents activating an NOS-dependent pathway is mediated by glucose metabolite lactate. PMID:23909711

  14. Omega-3 Polyunsaturated Fatty Acids in Treatment of Patients with Coronary Heart Disease and Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Aisulu T. Mussagalieva, MD, PhD

    2012-03-01

    Full Text Available Increased platelet aggregation is one of the major risk factors for cardiovascular events. However, recent studies have demonstrated the inhibition of platelet aggregation by omega-3 PUFAs. The aim of this work was to study the effect of the addition of omega-3 PUFAs to the combination of aspirin and clopidogrel on the platelet aggregation in patients with coronary heart disease. In all, 40 patients with coronary heart disease and diabetes mellitus type 2 undergoing PCI with stent implantation were included in the study. Clopidogrel in a 300 mg loading dose was given after drawing blood for baselinemeasurement of ADP-induced platelet aggregation. Patients were randomized into two groups. The first group included 20 patients who received 75 mg clopidogrel once daily, 100 mg aspirin once daily and 1000 mg omega-3 PUFAs daily. The second group included 20 patients who received 75 mg clopidogrel once daily and 100 mg aspirin daily. The ADP– induced platelet aggregation was performed twice, once before clopidogrel administration and once after one month. All the patients were genotyped for CYP2C19 polymorphism. No significant differences were noted among the genotype and allele frequencies of the cytochrome CYP2C19 gene between the two groups. The addition of omega-3 PUFAs to the standard dual antiplatelet therapy of aspirin and clopidogrel significantly decreased the ADP-induced platelet aggregation.

  15. [Platelet hyperreactivity and antiaggregatory properties of nootropic drugs under conditions of alloxan-induced diabetes in rats].

    Science.gov (United States)

    Zhiliuk, V I; Levykh, A É; Mamchur, V I

    2012-01-01

    The effects of nootropic drugs (noopept, pentoxifylline, piracetam, pramiracetam, Ginkgo biloba extract, entrop, cerebrocurin and citicoline) on platelet aggregation in rats with experimental diabetes have been studied. It is established that all these drugs exhibit an inhibitory action of various degrees against platelet hyperreactivity under conditions of chronic hyperglycemia. The maximum universality of the antiaggregatory action is characteristic of pramiracetam, entrop and Ginkgo biloba extract. PMID:22702111

  16. Proteinase-activated receptors 1 and 4 counter-regulate endostatin and VEGF release from human platelets

    OpenAIRE

    Ma, Li; Perini, Rafael; McKnight, Webb; Dicay, Michael; Klein, Andre; Hollenberg, Morley D.; Wallace, John L

    2004-01-01

    The roles of proteinase-activated receptors (PARs) in platelet functions other than aggregation are not well understood. Among these is the release of factors that regulate the process of angiogenesis, such as endostatin and VEGF, which, respectively, inhibit and promote angiogenesis. PAR1 and PAR4 are expressed on the surface of human platelets and can be activated by thrombin. In the present study, we have attempted to determine the roles of PAR1 and PAR4 in regulating release of endostatin...

  17. Structure-guided creation of AcAP5-derived and platelet targeted factor Xa inhibitors.

    Science.gov (United States)

    Zhu, Yuanjun; Lin, Yuan; Liu, Aihua; Shui, Mengyang; Li, Ruyi; Liu, Xiaoyan; Hu, Wenhui; Wang, Yinye

    2015-06-15

    Anticoagulants and anti-platelet agents are simultaneously administrated in clinical practice (i.e. percutaneous coronary intervention), which cause significant risk of systemic bleeding. Targeted delivery of anticoagulants to the activated platelets at sites of vascular injuries may condense the site-specific anticoagulant effect and reduce the hemorrhage side effects in uninjured vessels. To this end, we prepared three ancylostoma caninum anticoagulant peptide 5 (AcAP5) variants NR1, NR2 and NR3 engineered with a platelet-binding Arg-Gly-Asp (RGD) motif and eva