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https://www.readbyqxmd.com/read/28345287/contribution-of-platelet-p2y12-receptors-to-chronic-complete-freund-s-adjuvant-induced-inflammatory-pain
#1
K Bekő, B Koványi, F Gölöncsér, G Horváth, Á Dénes, Zs Környei, B Botz, Zs Helyes, C E Müller, B Sperlágh
BACKGROUND: P2Y12 receptor antagonists are widely used in clinical practice to inhibit platelet aggregation. P2Y12 receptors are also known to regulate different forms of pain as well as local and systemic inflammation. However it is not known if platelet P2Y12 receptors contribute to these effects. OBJECTIVES: In this study, we explored the contribution of platelet P2Y12 receptors to chronic inflammatory pain in mice. METHODS: Complete Freund's adjuvant (CFA)-induced chronic inflammatory pain was induced in wild-type and P2ry12 gene-deficient mice (P2ry12-/-), and the potent, direct-acting and reversible P2Y12 receptor antagonists, PSB-0739, and cangrelor were used...
March 27, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28344655/interactions-among-cox-2-gpiiia-and-p2y1-variants-are-associated-with-aspirin-responsiveness-and-adverse-events-in-patients-with-ischemic-stroke
#2
Xingyang Yi, Zhao Han, Qiang Zhou, Jing Lin, Chun Wang
BACKGROUND: The effect of gene variants and their interactions on response to aspirin and clinical adverse outcomes after an acute ischemic stroke (IS) is not fully understood. The aim of this study was to investigate the association of aspirin-relevant gene variants and their interactions with clinical adverse outcomes in IS patients taking aspirin. METHODS: A total of 14 variants from six genes encoding COX enzymes (COX-1, COX-2), platelet membrane receptors (TXAS1, P2Y1, P2Y12) and glycoprotein receptor (GPIIIa) were examined in 850 acute IS patients...
March 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/28344198/radiosensitizing-effect-of-p2x7-receptor-antagonist-on-melanoma-in-vitro-and-in-vivo
#3
Keisuke Tanamachi, Keisuke Nishino, Natsuki Mori, Toshihiro Suzuki, Sei-Ichi Tanuma, Ryo Abe, Mitsutoshi Tsukimoto
Melanoma is highly malignant, and generally exhibits radioresistance, responding poorly to radiation therapy. We previously reported that activation of P2X7, P2Y6, and P2Y12 receptors is involved in the DNA damage response after γ-irradiation of human lung adenocarcinoma A549 cells. However, it is not clear whether these receptors are also involved in the case of melanoma cells, although P2X7 receptor is highly expressed in various cancers, including melanoma. Here, we show that P2X7 receptor antagonist enhances radiation-induced cytotoxicity in B16 melanoma cells in vitro and in vivo...
March 24, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28342632/the-pharmacodynamics-of-low-and-standard-doses-of-ticagrelor-in-patients-with-end-stage-renal-disease-on-hemodialysis
#4
Jin Sug Kim, Jong Shin Woo, Jin Bae Kim, Woo-Shik Kim, Tae Won Lee, Kwon Sam Kim, Chun Gyoo Ihm, Weon Kim, Kyung Hwan Jeong
BACKGROUND: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) respond poorly to clopidogrel. We assessed the utility of low-dose ticagrelor in ESRD patients on maintenance HD. METHODS: In this single-center, prospective, randomized pharmacodynamic study, 52 ESRD patients on HD were prescribed clopidogrel (300mg loading dose [LD], then 75mg daily), standard-dose ticagrelor (180mg LD, then 90mg twice daily), or low-dose ticagrelor (90mg LD, then 90mg daily) for 14days...
March 9, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28336370/purinergic-p2y6-receptors-a-new-therapeutic-target-of-age-dependent-hypertension
#5
REVIEW
Caroline Sunggip, Akiyuki Nishimura, Kakeru Shimoda, Takuro Numaga-Tomita, Makoto Tsuda, Motohiro Nishida
Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertension, although the control rates remain unsatisfactory especially in the elder patients with hypertension. Purinergic receptors, activated by adenine, uridine nucleotides and nucleotide sugars, play pivotal roles in many biological processes, including platelet aggregation, neurotransmission and hormone release, and regulation of cardiovascular contractility...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28335837/potent-p2y12-inhibitors-in-men%C3%A2-versus%C3%A2-women-a%C3%A2-collaborative%C3%A2-meta-analysis%C3%A2-of%C3%A2-randomized%C3%A2-trials
#6
Emily S Lau, Eugene Braunwald, Sabina A Murphy, Stephen D Wiviott, Marc P Bonaca, Steen Husted, Stefan K James, Lars Wallentin, Peter Clemmensen, Matthew T Roe, E Magnus Ohman, Robert A Harrington, Jessica L Mega, Deepak L Bhatt, Marc S Sabatine, Michelle L O'Donoghue
BACKGROUND: Sex-specific differences in response to antiplatelet therapies have been described. Whether women and men derive comparable benefit from intensification of antiplatelet therapy remains uncertain. OBJECTIVES: The study investigated the efficacy and safety of the potent P2Y12 inhibitors in patients with coronary artery disease. METHODS: A collaborative sex-specific meta-analysis was conducted of phase III or IV randomized trials of potent P2Y12 inhibitors, including prasugrel, ticagrelor, and intravenous cangrelor...
March 28, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28335443/pharmacokinetic-and-pharmacodynamic-responses-to-clopidogrel-evidences-and-perspectives
#7
REVIEW
Yan-Jiao Zhang, Mu-Peng Li, Jie Tang, Xiao-Ping Chen
Clopidogrel has significantly reduced the incidence of recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, recurrence events still remain, which may be partly due to inadequate platelet inhibition by standard clopidogrel therapy. Genetic polymorphisms involved in clopidogrel's absorption, metabolism, and the P2Y12 receptor may interfere with its antiplatelet activity. Recent evidence indicated that epigenetic modification may also affect clopidogrel response...
March 14, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28331925/biological-effects-of-ticagrelor-over-clopidogrel-in-patients-with-stable-coronary-artery-disease-and-chronic-obstructive-pulmonary-disease
#8
Gianluca Campo, Francesco Vieceli Dalla Sega, Rita Pavasini, Giorgio Aquila, Francesco Gallo, Francesca Fortini, Elisabetta Tonet, Paolo Cimaglia, Annamaria Del Franco, Gabriele Pestelli, Alessandro Pecoraro, Marco Contoli, Cristina Balla, Simone Biscaglia, Paola Rizzo, Roberto Ferrari
Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin...
March 23, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28329746/genotyping-platelet-activation-and-cardiovascular-outcome-in-patients-after-percutaneous-coronary-intervention-two-pieces-of-the-puzzle-of-clopidogrel-resistance
#9
Gerasimos Siasos, Evangelos Oikonomou, Manolis Vavuranakis, Eleni Kokkou, Konstantinos Mourouzis, Sotiris Tsalamandris, Marina Zaromitidou, Stamatios Kioufis, Vasiliki Tsigkou, Spyridon Deftereos, Christodoulos Stefanadis, Dimitris Tousoulis
OBJECTIVES: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. METHODS: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI...
March 22, 2017: Cardiology
https://www.readbyqxmd.com/read/28329196/diabetic-patients-with-acute-coronary-syndromes-in-contemporary-european-registries-characteristics-and-outcomes
#10
Maddalena Lettino, Pontus Andell, Uwe Zeymer, Petr Widimsky, Nicolas Danchin, Alfredo Bardaji, Jose A Barrabes, Angel Cequier, Marc J Claeys, Leonardo De Luca, Jakob Dörler, David Erlinge, Paul Erne, Patrick Goldstein, Sasha M Koul, Gilles Lemesle, Thomas F Lüscher, Christian M Matter, Gilles Montalescot, Dragana Radovanovic, Jose Lopez Sendón, Petr Tousek, Franz Weidinger, Clive F M Weston, Azfar Zaman, Jin Li, J Wouter Jukema
Aims: Among patients with acute coronary syndromes (ACS), those with diabetes mellitus (DM) are at particularly high risk of recurrent cardiovascular events and premature death. We aimed to provide a descriptive overview of unadjusted analyses of patient characteristics, ACS management, and outcomes up to 1 year after hospital admission for an ACS/index-ACS event, in patients with DM in contemporary registries in Europe. Methods and results: A total of 10 registries provided data in a systematic manner on ACS patients with DM (total n =28 899), and without DM (total n= 97 505)...
March 10, 2017: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/28325638/clinically-significant-bleeding-with-low-dose-rivaroxaban-versus-aspirin-in-addition-to-p2y12-inhibition-in-acute-coronary-syndromes-gemini-acs-1-a-double-blind-multicentre-randomised-trial
#11
E Magnus Ohman, Matthew T Roe, P Gabriel Steg, Stefan K James, Thomas J Povsic, Jennifer White, Frank Rockhold, Alexei Plotnikov, Hardi Mundl, John Strony, Xiang Sun, Steen Husted, Michal Tendera, Gilles Montalescot, M Cecilia Bahit, Diego Ardissino, Héctor Bueno, Marc J Claeys, Jose C Nicolau, Jan H Cornel, Shinya Goto, Róbert Gábor Kiss, Ümit Güray, Duk-Woo Park, Christoph Bode, Robert C Welsh, C Michael Gibson
BACKGROUND: Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2·5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months...
March 17, 2017: Lancet
https://www.readbyqxmd.com/read/28322086/viability-of-sh-sy5y-cells-is-associated-with-purinergic-p2-receptor-expression-alterations
#12
Arda Örçen, Vuslat Yilmaz, Murat Giriş, Uğur Akcan, Erdem Tüzün, Gaye Erten
To investigate the role of metabotrophic purinergic P2Y receptors in neuroblastoma cell survival, expression of P2 receptors by normal mouse (C57BL/6) brain and human neuroblastoma SH-SY5Y cells was investigated by Western blot and real time PCR studies. Viability of SH-SY5Y cells treated with purinergic receptor antagonists suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS) was evaluated by MTT assay and flow cytometry. In the brain samples of C57BL/6 mice, expressions of P2Y4 and P2X7 were significantly reduced, whereas that of P2Y1 was significantly elevated in an age-dependent manner...
March 2017: Acta Biologica Hungarica
https://www.readbyqxmd.com/read/28322016/haemostatic-effects-of-the-ticagrelor-antidote-medi2452-in-pigs-treated-with-ticagrelor-on-a-background-of-aspirin
#13
Susanne Pehrsson, Karin J Johansson, Annika Janefeldt, Ann-Sofie Sandinge, Sufyan Maqbool, Joanne Goodman, José Sanchez, Joachim Almquist, Peter Gennemark, Sven Nylander
BACKGROUND: Ticagrelor, a P2Y12 antagonist, is approved for the prevention of thromboembolic events. However, antiplatelet therapies carry a risk of bleeding. OBJECTIVE: To explore the haemostatic effects of MEDI2452, an antidote for ticagrelor. METHODS: Pigs, pre-treated with aspirin, were given an intravenous infusion of ticagrelor or vehicle. After stop of infusion, a piece of a liver lobe was cut off, and a bolus of MEDI2452 or vehicle was administered intravenously...
March 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28321022/administration-of-ticagrelor-and-double-dose-clopidogrel-based-on-platelet-reactivity-determined-by-verifynow-p2y12-for-chinese-subjects-after-elective-pci
#14
Xi Wu, Gang Liu, Jie Lu, Xin-Xin Zheng, Jin-Gang Cui, Xue-Yan Zhao, Xiao-Hong Huang
Previous studies have identified high on treatment platelet reactivity (HTPR) as a potent factor predicting ischemic events for patients with coronary heart disease. We assessed the efficacy and safety of ticagrelor (90 mg twice-daily) and double-dose of clopidogrel (150 mg once-daily) among Chinese patients for elective percutaneous coronary intervention. We enrolled 40 patients with HTPR from among 317 patients with non-ST-segment elevation acute coronary syndromes after a successful elective percutaneous coronary intervention (PCI)...
March 17, 2017: International Heart Journal
https://www.readbyqxmd.com/read/28296036/targeting-of-c-type-lectin-like-receptor-2-or-p2y12-for-the-prevention-of-platelet-activation-by-immunotherapeutic-cpg-oligodeoxynucleotides
#15
C Delierneux, N Donis, L Servais, O Wéra, C Lecut, M Vandereyken, L Musumeci, S Rahmouni, J Schneider, J A Eble, P Lancellotti, C Oury
BACKGROUND: Synthetic phosphorothioate-modified CpG oligodeoxynucleotides (CpG ODNs) display potent immunostimulatory properties that are widely exploited in clinical trials of anticancer treatment. Unexpectedly, a recent study indicates that CpG ODNs activate human platelets via the immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptor glycoprotein VI. OBJECTIVE: To further analyze the mechanisms of CpG ODN-induced platelet activation and identify potential inhibitory strategies...
March 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28290994/derivation-and-validation-of-the-predicting-bleeding-complications-in-patients-undergoing-stent-implantation-and-subsequent-dual-antiplatelet-therapy-precise-dapt-score-a-pooled-analysis-of-individual-patient-datasets-from-clinical-trials
#16
Francesco Costa, David van Klaveren, Stefan James, Dik Heg, Lorenz Räber, Fausto Feres, Thomas Pilgrim, Myeong-Ki Hong, Hyo-Soo Kim, Antonio Colombo, Philippe Gabriel Steg, Thomas Zanchin, Tullio Palmerini, Lars Wallentin, Deepak L Bhatt, Gregg W Stone, Stephan Windecker, Ewout W Steyerberg, Marco Valgimigli
BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. METHODS: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events...
March 11, 2017: Lancet
https://www.readbyqxmd.com/read/28290914/-nonplatelet-effects-of-ticagrelor
#17
V V Boiko, G N Soboleva
This review summarizes current knowledge concerning "nonplatelet effects of P2Y12 receptor antagonist ticagrelor. We show the experimental and clinical evidence that ticagrelor increases plasma concentration of adenosine as a potential mechanism of additive effects of ticagrelor. In addition, we sought to compare the clinical profile of ticagrelor with pharmacological effects of adenosine and discuss from this point of view the effects of ticagrelor on vascular tone, cardiac electrophysiology, ischemia/reperfusion injury, immunity and inflammatory reactions, peripheral nerves...
July 2016: Kardiologiia
https://www.readbyqxmd.com/read/28288963/platelet-reactivity-and-clinical-outcomes-after-coronary-artery-implantation-of-drug-eluting-stents-in-subjects-with-peripheral-arterial-disease-analysis-from-the-adapt-des-study-assessment-of-dual-antiplatelet-therapy-with-drug-eluting-stents
#18
Rajesh Gupta, Ajay J Kirtane, M Ozgu Ozan, Bernhard Witzenbichler, Michael J Rinaldi, D Christopher Metzger, Giora Weisz, Thomas D Stuckey, Bruce R Brodie, Roxana Mehran, Ori Ben-Yehuda, Gregg W Stone
BACKGROUND: Patients with peripheral arterial disease (PAD) have high rates of adverse cardiovascular events after percutaneous coronary intervention and may additionally have heightened platelet reactivity. This study assessed the relationship between platelet reactivity and clinical outcomes after percutaneous coronary interventions among subjects with and without PAD. METHODS AND RESULTS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents...
March 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28279968/newly-formed-reticulated-platelets-undermine-pharmacokinetically-short-lived-antiplatelet-therapies
#19
Paul C Armstrong, Thomas Hoefer, Rebecca B Knowles, Arthur Tucker, Melissa A Hayman, Plinio M Ferreira, Melissa V Chan, Timothy D Warner
OBJECTIVE: Aspirin together with thienopyridine P2Y12 inhibitors, commonly clopidogrel, is a cornerstone of antiplatelet therapy. However, many patients receiving this therapy display high on-treatment platelet reactivity, which is a major therapeutic hurdle to the prevention of recurrent thrombotic events. The emergence of uninhibited platelets after thrombopoiesis has been proposed as a contributing factor to high on-treatment platelet reactivity. Here, we investigate the influences of platelet turnover on platelet aggregation in the face of different dual-antiplatelet therapy strategies...
March 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28279076/triple-antithrombotic-therapy-with-aspirin-p2y12-inhibitor-and-warfarin-after-percutaneous-coronary-intervention
#20
Nathan J Verlinden, James C Coons, Carlo J Iasella, Sandra L Kane-Gill
BACKGROUND: Triple antithrombotic therapy is used in patients who require systemic anticoagulation and undergo percutaneous coronary intervention (PCI) requiring dual antiplatelet therapy. Bleeding with this combination is significant; however, few studies have described outcomes with the use of newer oral P2Y12 inhibitors in this setting. OBJECTIVES: We aimed to compare outcomes among patients prescribed triple therapy with prasugrel or ticagrelor compared to triple therapy with clopidogrel in patients who underwent PCI and required warfarin...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
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