A5089627879- Antiplatelet Therapy and Cardiovascular Diseases
- Platelet Disorders and Treatments
- Venous Thromboembolism Diagnosis and Management
- Inflammatory mediators and NSAID effects
- Blood properties and coagulation
- Acute Ischemic Stroke Management
- Atrial Fibrillation Management and Outcomes
- Heparin-Induced Thrombocytopenia and Thrombosis
- Adenosine and Purinergic Signaling
- Sesquiterpenes and Asteraceae Studies
- Synthesis of β-Lactam Compounds
- Hormonal and reproductive studies
- Acute Myocardial Infarction Research
- Analytical Methods in Pharmaceuticals
- Cerebrovascular and Carotid Artery Diseases
- Cell Adhesion Molecules Research
- Blood groups and transfusion
- Plant Toxicity and Pharmacological Properties
- Blood disorders and treatments
- Receptor Mechanisms and Signaling
- Eicosanoids and Hypertension Pharmacology
- Diabetes Treatment and Management
- Phytochemistry and Biological Activities
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Trauma, Hemostasis, Coagulopathy, Resuscitation
Queen's Medical Centre
2007-2020
University of Nottingham
2010-2020
Nottingham City Hospital
1985-2016
University College London
1985-2013
University of Leicester
2013
Nottingham University Hospitals NHS Trust
2006
Jena University Hospital
1996-2003
Queen's University
1985-1998
Leicester Royal Infirmary
1997
Centre National de la Recherche Scientifique
1996
Aims This double-blind, parallel-group study was conducted to assess the pharmacodynamics, pharmacokinetics, and safety of AZD6140, first oral, reversible adenosine diphosphate (ADP) receptor antagonist.
Adenosine diphosphate (ADP) is an important platelet agonist and ADP released from dense granules amplifies responses to other agonists. There are three known subtypes of receptor on platelets: P2X 1 , P2Y P 2T receptors. Sustained ADP‐induced aggregation requires co‐activation AR‐C69931MX, a selective antagonist novel antithrombotic agent, was studied characterize further the function receptor. The roles thromboxane A 2 were assessed using A2P5P aspirin respectively. Aggregation measured by...
BackgroundIntensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive (combined aspirin, clopidogrel, dipyridamole) that guideline-based therapy.MethodsWe did an international, prospective, randomised, open-label, blinded-endpoint trial adult participants ischaemic stroke or transient attack (TIA) within 48 h onset. Participants...
Platelet-leukocyte interactions are recognised to have pro-inflammatory effects, which may be important in the pathophysiology of ischaemic heart disease. Clopidogrel and novel intravenous antithrombotic agent AR-C69931MX act at level platelet P2Y12 receptor, is known amplify activation, aggregation other responses induced by numerous agonists. We studied effects clopidogrel aspirin on ADP-induced platelet-leukocyte conjugate formation P-selectin expression healthy volunteers. The...
AbstractWe compared the antiplatelet effects of clopidogrel and intravenous platelet P2Y 12 receptor antagonist AR-C69931MX, which acts on same as by a different reversible mechanism and, unlike clopidogrel, is active in vitro . Thirteen patients with acute coronary syndromes entered into phase II study AR-C69931MX (Group 1) eight undergoing intracoronary stent implantation treated 2) were studied using whole blood single-platelet counting aggregation assay. Group 2 also turbidimetry ADP...
The Ultra-Flo 100 Whole Blood Platelet Counter has proved a useful tool for measuring platelet aggregation in whole blood, the extent of being deduced from number single platelets that remain. technique allowed us to show aggregate spontaneously citrated blood and heparinized but not collected into EDTA. occurs during storage its rate is enhanced by stirring it more readily when been exposed plastic rather than glass. It much some individuals others process may involve adenosine diphosphate...
Abstract It has been suggested that extracts of feverfew may inhibit platelet behaviour via effects on sulphydryl groups. In the present study we have obtained evidence for such a mode action. (i) Compounds contain groups as cysteine and N-(2-mercaptopropionyl)glycine prevented inhibition by feverfew. (ii) Feverfew parthenolide (one active components feverfew) dramatically reduced number acid-soluble in platelets. This effect occurred at concentrations similar to those inhibited secretory...
Summary Tissue factor (TF) is the most important initiator of intravascular coagulation. Platelets contribute to TF exposure on monocytes, but mechanism not completely understood. Here we examined possibility that platelets may release can be transferred monocytes by platelet-derived microvesicles. When human citrated platelet-rich plasma was incubated with collagen there an increase in levels and CD62P. Incubation obtained from collagen-stimulated PRP a sediment red white blood cells...
ADP plays a major role in the amplification of platelet aggregation induced by other agonists. initiates activation via P2Y(1) receptor and amplifies P2Y(12) receptor. Using selective antagonist A2P5P AR-C69931MX, we assessed relative contributions to hirudin-anticoagulated whole blood PAF, 5HT, epinephrine, TRAP, streptokinase, U46619 collagen. The effects aspirin were concurrently. AR-C69931MX variably inhibited most agonists studied, whereas only streptokinase In some experiments, yielded...
Abstract Extracts of the herb feverfew inhibit human blood platelet aggregation and secretion induced by a number agents in-vitro this may relate to beneficial effects in migraine. We previously identified several compounds with antisecretory activity platelets using adrenaline as stimulant. In present study, we have compared inhibitory one these compounds, parthenolide, that crude extract. The both on [14C]5-HT from different stimulants were determined. activating studied included phorbol...
Three physicochemical methods (HPLC, NMR spectroscopy, and HPLC of a derivative) have been used to measure parthenolide in authenticated Tanacetum parthenium (feverfew) several commercial purported feverfew products. A bioassay based on inhibition the secretory activity blood platelets by extracts comparison with was also used. Similar results were obtained for all three assays bioassay. Thus different methodologies yield consistent values content preparations. Parthenolide appears be mainly...
There is growing interest in possible beneficial effects of specific dietary components on cardiovascular health. Platelets and leukocytes contribute to arterial thrombosis inflammatory processes. Previous studies performed vitro have demonstrated inhibition platelet function by (−)-epicatechin (+)-catechin, flavan-3-ols (flavanols) that are present several foods including some cocoas. Also, modest has been observed ex vivo after the consumption flavanol-containing cocoa products healthy...
Feverfew, reputed by folklore to be effective in arthritis, has vitro properties that could beneficial the control of inflammatory disease. Forty one female patients with symptomatic rheumatoid arthritis received either dried chopped feverfew (70-86 mg) or placebo capsules once daily for six weeks. Allocation was random and not known patient observer. Variables assessed included stiffness, pain (visual analogue scale), grip strength, articular index, full blood count, erythrocyte...
The platelet P2Y12 receptor is the target of clopidogrel therapy, which has been shown to reduce thromboembolic complications atherosclerotic disease but limitations in terms variability response and irreversibility effect. This also a for ticagrelor (AZD6140), first reversibly binding oral antagonist that does not require metabolic activation yields more consistent inhibition aggregation than therapy. Single nucleotide polymorphisms (SNPs) have described gene this (P2RY12), some associated...
Receptors for prostanoids on platelets include the EP3 receptor which natural agonist is inflammatory mediator prostaglandin E(2) (PGE(2)) produced in atherosclerotic plaques. implicated atherothrombosis and an antagonist might provide lesion-specific antithrombotic therapy. DG-041 (2,3-dichlorothiophene-5-sulfonic acid, 3-[1-(2,4-dichlorobenzyl)-5-fluoro-3-methyl-1H-indol-7-yl]acryloylamide) a direct-acting currently being evaluated Phase 2 clinical trials. We have examined contributions of...
The effects of prostaglandin E(2) (PGE(2)) on platelet function are believed to be the result opposing mechanisms that lead both enhancement and inhibition function. Enhancement is known via EP3 receptors linked G(i) adenylyl cyclase. However, involved in have not been fully defined. Here we used measurements aggregation, calcium signaling P-selectin expression assess induced by activating factor (PAF), thrombin receptor peptide (TRAP-6) thromboxane A(2) mimetic U46619 respectively,...