A5059950825- Inflammatory mediators and NSAID effects
- Antiplatelet Therapy and Cardiovascular Diseases
- Platelet Disorders and Treatments
- Eicosanoids and Hypertension Pharmacology
- Nitric Oxide and Endothelin Effects
- Extracellular vesicles in disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Respiratory and Cough-Related Research
- Blood properties and coagulation
- Respiratory Support and Mechanisms
- Asthma and respiratory diseases
- Cancer, Stress, Anesthesia, and Immune Response
- Forensic Toxicology and Drug Analysis
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Inflammatory Biomarkers in Disease Prognosis
- Blood Coagulation and Thrombosis Mechanisms
- Caveolin-1 and cellular processes
- GDF15 and Related Biomarkers
- Adenosine and Purinergic Signaling
- Pharmacology and Obesity Treatment
- Nuclear Receptors and Signaling
- Estrogen and related hormone effects
- Renin-Angiotensin System Studies
Lung Institute
2024
Imperial College London
2020-2024
Queen Mary University of London
2016-2020
University of Reading
2020
Universidade de São Paulo
2015-2017
Versar (United States)
2017
William Harvey Research Institute
2016-2017
Swansea University
2016
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 major therapeutic hurdle to the prevention recurrent thrombotic events. The emergence uninhibited platelets after thrombopoiesis has been proposed as contributing factor reactivity. Here, we investigate influences turnover on aggregation in face different dual-antiplatelet...
Platelet activation causes the release of extracellular vesicles, which a small proportion contain respiratory competent mitochondria. Mitochondria are integral for energy production and in regulation apoptotic pathways. However, existence mitochondria highlights potential new role intercellular communication. We hypothesised that platelet vesicles containing could be taken up by circulatory cells alter their function. In this work we demonstrate interact with internalised neutrophils. Flow...
Abstract Platelet-derived extracellular vesicles (PDEVs) are the most abundant amongst all types of EVs in circulation. However, mechanisms leading to PDEVs release, their role coagulation and phenotypic composition poorly understood. from washed platelets were generated using different stimuli characterised nanoparticle tracking analysis. Procoagulant properties evaluated by fluorescence flow cytometry calibrated automated thrombography. plasma isolated concentrated a novel protocol...
Platelets release platelet-derived extracellular vesicles (PDEVs) upon activation - in a process that is regulated by generation of reactive oxygen species (ROS). Platelet NADPH oxidase-1 (Nox-1) contributes to ROS and thrombus formation downstream the collagen receptor GPVI.We aimed investigate whether PDEVs contain Nox-1 this relevant for PDEV-induced platelet activation.PDEVs were isolated through serial centrifugation after with thrombin agonist TRAP-6 (activated PDEVs) or absence...
Through the production of prostacyclin, cyclooxygenase (COX)-2 protects cardiorenal system. Asymmetric dimethylarginine (ADMA), is a biomarker cardiovascular and renal disease. Here we determined relationship between COX-2/prostacyclin, ADMA, function in mouse human models.
The recent surge in recreational (non-medical) use of nitrous oxide (N 2 O, also known as ‘laughing gas’) often by inhaling it from balloons, has attracted the attention some politicians with calls to control its possession under United Kingdom (UK) Misuse Drugs Act 1971 (currently selling, but not possession, for is controlled Psychoactive Substances 2016). Meanwhile, nitric monoxide (NO) delivered alkyl nitrites, ‘poppers’ raised concerns, unlike N was 2016 Act. To inform future-decision...
Despite the interwoven nature of platelet activation and coagulation system in thrombosis, few studies relate both analysis protein cellular parts same population. In present study, we use matched ex vivo samples to determine influences standard antiplatelet therapies on function advanced rheological analyses assess clot formation. Healthy volunteers were recruited following fully informed consent then treated for 7 days with single therapy aspirin (75 mg) or prasugrel (10 dual (DAPT) using...
Substantial platelet inhibition was observed 3 days after a single administration of acetylsalicylic acid 81 mg to healthy volunteers. Here we investigate prostaglandin E2 (PGE2 ) antrum concentrations and gastrointestinal symptoms in two treatment groups: one receiving losartan every day the other days. Twenty-eight volunteers from both sexes received either 50 daily or with placebo on Therapy delivered for 30 groups. Gastric endoscopy performed before period. Biopsies were collected PGE2...
BackgroundEndothelium‐derived prostacyclin and nitric oxide elevate platelet cyclic nucleotide levels maintain quiescence. We previously demonstrated that a synergistic relationship exists between nucleotides P2Y12 receptor inhibition. A number of clinically approved drug classes can modulate tone in platelets including activators NO‐sensitive guanylyl cyclase (GC) phosphodiesterase (PDE) inhibitors. However, the doses required to inhibit produce numerous side effects headache.ObjectiveWe...
The Standard care vs. Celecoxib Outcome Trial (SCOT) found similar risk of cardiovascular events with traditional non-steroidal anti-inflammatory drugs (NSAIDs) and the cyclooxygenase-2-selective drug celecoxib. While pre-clinical work has suggested roles for vascular renal dysfunction in NSAID toxicity, our understanding these mechanisms remains incomplete. A
In 2015 and 2016, during the debates that culminated in The Psychoactive Substances Act both houses of UK parliament debated pharmacology nitric oxide amyl nitrites, otherwise known as “poppers”. original draft Bill had recommended poppers should be made illegal. However, after strong opposition inside Conservative party, ruling party at time, government found a way to not ban them by claiming they were psychoactive. Nitrous oxide, another recreational gas, was also possible target but this...
<h3>Methods</h3> Mice were pre-treated with vehicle, prasugrel (0.3 mg/kg), cinaciguat mg/kg) + dipyridamole (2.0 or (triple) and anesthetized. To measure in vivo thrombus formation, the carotid artery was then exposed thrombosis induced by placement of a piece filter paper saturated 10% ferric chloride contact adventitial surface vessel for 3 minutes. Carotid blood flow monitored Doppler probe time to form an occlusive being taken as required stop flowing completely >1 Time occlusion...
Abstract Background Despite being one of the most commonly used and readily available drugs worldwide, we still do not understand why non-steroidal anti-inflammatory (NSAIDs) increase cardiovascular risk. A proteomics approach may provide mechanistic insight into how COX-2 protects system. Purpose To use SWATH to identify biomarkers in NSAID users who go onto have a event. Methods case control study was designed using Standard Care Versus Celecoxib Outcome Trial (SCOT) biobank (1). Serum...
Introduction and Hypothesis: Through the production of prostacyclin (PGI2), cyclooxygenase (COX)-2 protects cardio-renal system. Restraining methylarginines (ADMA, SDMA), which are biomarkers renal cardiovascular disease inhibitors (ADMA) cardioprotective endothelial nitric oxide synthase (eNOS), has been suggested as a contributory pathway. However, relationship between function, COX-2 remains unclear. Methods: Using plasma from genetically modified mice with germline global deletion or PGI...
Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme cyclooxygenase (COX)2 but their use increases thrombotic risk. We have shown that COX2 inhibition plasma methylarginines ADMA and LNMMA in mice man. Methylarginines are controlled kidney circulate causing of anti-thrombotic vascular NO competing with L-arginine for active site eNOS. However, causative links between renal (which is expressed predominately fibroblasts), thrombosis remain unproven....
Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs), which work by blocking cyclooxygenase (COX)-2 can increase cardiovascular risk up to 30% after 2 weeks of use and in animal models augments thrombosis. However, the effect NSAIDs loss COX-2 on endothelial function blood flow remains incompletely understood. A plausible explanation is inhibition affects inhibiting prostacyclin and/or reducing nitric oxide synthase (eNOS) activity/expression. We hypothesised that with celecoxib will...