A5065026165- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- S100 Proteins and Annexins
- Lung Cancer Diagnosis and Treatment
- Respiratory Support and Mechanisms
- Antimicrobial Peptides and Activities
- Nosocomial Infections in ICU
- Immune Response and Inflammation
- COVID-19 Clinical Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Photodynamic Therapy Research Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Bacterial Infections and Vaccines
- Cell Adhesion Molecules Research
- Respiratory viral infections research
- Pneumonia and Respiratory Infections
- Computational Drug Discovery Methods
- Biosensors and Analytical Detection
- Esophageal Cancer Research and Treatment
- Protease and Inhibitor Mechanisms
- Advanced Optical Sensing Technologies
- Pulmonary Hypertension Research and Treatments
- Galectins and Cancer Biology
- Bacterial biofilms and quorum sensing
University of Edinburgh
2014-2023
Centre for Inflammation Research
2014-2023
Queen's Medical Centre
2015-2023
The Queen's Medical Research Institute
2016-2021
Engineering and Physical Sciences Research Council
2017-2019
Queen's University
2015
Medical Research Institute
2015
Rationale: Acute lung injury (ALI) is an important cause of morbidity and mortality, with no currently effective pharmacological therapies. Neutrophils have been specifically implicated in the pathogenesis ALI, there has significant research into mechanisms early neutrophil recruitment, but those controlling later phases emigration that characterize disease are poorly understood.Objectives: To determine influence peripheral blood monocytes (PBMs) established ALI.Methods: In a murine model...
BackgroundMany repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate.MethodsWe present the findings a phase Ib/IIa open label, platform randomised controlled trial intravenous hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly standard care (SoC), or an alternative therapy. Nafamostat was administered as...
A fluorescently labelled ubiquicidin peptide enables bacterial detection in human lung tissue<italic>in vitro</italic>.
Respiratory infections in mechanically ventilated patients caused by Gram-negative bacteria are a major cause of morbidity. Rapid and unequivocal determination the presence, localization, abundance is critical for positive resolution could be used patient stratification monitoring treatment efficacy. Here, we developed an situ approach to visualize bacterial species cellular infiltrates distal human lungs real time. We optical endomicroscopy water-soluble imaging probe based on antimicrobial...
<h3>Background</h3> Acute respiratory distress syndrome (ARDS) is an often fatal neutrophil-dominant lung disease. Although influenced by multiple proinflammatory mediators, identification of suitable therapeutic candidates remains elusive. We aimed to delineate the presence mitochondrial formylated peptides in ARDS and characterise functional importance formyl peptide receptor 1 (FPR1) signalling sterile inflammation. <h3>Methods</h3> Mitochondrial were identified bronchoalveolar lavage...
High circulating galectin-3 is associated with poor outcomes in patients coronavirus disease (COVID-19). We hypothesized that GB0139, a potent inhaled thiodigalactoside inhibitor antiinflammatory and antifibrotic actions, would be safely effectively delivered COVID-19 pneumonitis.
We demonstrate a fast two-color widefield fluorescence microendoscopy system capable of simultaneously detecting several disease targets in intact human ex vivo lung tissue. characterize the for light throughput from excitation emitting diodes, collection efficiency, and chromatic focal shifts. effectiveness instrument by imaging bacteria (Pseudomonas aeruginosa) describe mechanism bacterial detection through fiber bundle that uses blinking effects as they move front core providing objects...
A SPAD-based line sensor fabricated in 130 nm CMOS technology capable of acquiring time-resolved fluorescence spectra (TRFS) 8.3 milliseconds is presented.To the best our knowledge, this fastest time correlated single photon counting (TCSPC) TRFS acquisition reported to date.The an upgrade prior work and incorporates: i) parallelized interface from surrounding circuitry enabling high rate PC (19,000 lines/s) ii) novel time-gating architecture where detected photons OFF region are rejected...
Abstract Rapid in situ detection of pathogens coupled with high resolution imaging the distal human lung has potential to provide new insights and diagnostic utility patients whom pneumonia is suspected. We have previously described an antimicrobial peptide (AMP) Ubiquicidin (fragment UBI 29–41 ) labelled environmentally sensitive fluorophore that optically detected bacteria vitro but not ex vivo . Here, we describe further chemical development this compound demonstrate altering secondary...
Abstract Neutrophil activation is an integral process to acute inflammation and associated with adverse clinical sequelae. Identification of neutrophil in real time the lungs patients may permit biological stratification otherwise heterogenous cohorts typically defined by criteria. No methods for identifying currently exist. We developed a bespoke molecular imaging probe targeting three characteristic signatures activation: pinocytosis, phagosomal alkalinisation, human elastase (HNE)...
Human neutrophil elastase (HNE) is a serine protease, produced by polymorphonuclear neutrophils (PMNs), whose uncontrolled production has been associated with various inflammatory disease states as well tumour proliferation and metastasis. Here we report the development characterisation of an electrochemical peptide-based biosensor, which enables detection clinically relevant levels HNE. The sensing platform was characterised in terms its analytical performance, enzymatic cleavage kinetics...
The relentless rise in antimicrobial resistance is a major societal challenge and requires, as part of its solution, better understanding bacterial colonization infection. To facilitate this, we developed highly efficient no-wash red optical molecular imaging agent that enables the rapid, selective, specific visualization Gram-positive bacteria through bespoke fiber-based delivery/imaging endoscopic device.We rationally designed no-wash, red, Gram-positive-specific (Merocy-Van) based on...
Abstract Serine proteases are released by neutrophils to act primarily as antimicrobial proteins but excessive and unbalanced serine protease activity results in serious host tissue damage. Here the synthesis of a novel chemical sensor based on multi-branched fluorescence quencher is reported. It super-silent, exhibiting no until de-quenched exemplar human neutrophil elastase, rapidly enters neutrophils, inhibited inhibitors. This allows live imaging intracellular within demonstrates that...
Objective and Impact Statement. There is a need to develop platforms delineating inflammatory biology of the distal human lung. We describe platform technology approach detect in situ enzyme activity observe drug inhibition lung using combination matrix metalloproteinase (MMP) optical reporters, fibered confocal fluorescence microscopy (FCFM), bespoke delivery device. Introduction . The development new therapeutic agents hindered by lack vivo experimental methodologies that can rapidly...
Nanocapsule-mediated eugenol release from an interpenetrating polymer network coating reduces bacterial binding on medical devices.
Summary Circadian ( c . 24 h) rhythms of physiology are entrained to either the environmental light‐dark cycle or timing food intake. In current work hypothesis that platelet turnover in mammals circadian and by intake was explored mice. Mice were 12 h cycles given ad libitum (AL) restricted access (RF) during light phase. Blood megakaryocytes then collected from mice every 4 for h. It found total reticulated numbers, plasma thrombopoietin (TPO) concentration mean size mature but not...
Objectives: Mild traumatic brain injury in the form of concussion is extremely common, and potential effects on pulmonary priming have been underestimated. The aim this study was to characterize response following mild assess susceptibility lung after a subsequent innocuous insult. Design: Experimental vivo study. Setting: University research laboratory. Subjects: Male CD1 mice. Interventions: We developed model concussive mice followed by acid microaspiration. To dependent role neutrophils...
Improving the speed and accuracy of bacterial detection is important for patient stratification to ensure appropriate use antimicrobials. To achieve this goal, development diagnostic techniques recognize presence in real-time at point-of-care required. Optical imaging direct identification bacteria within host an attractive approach. Several attempts chemical probe design validation have been investigated, however none yet successfully translated into clinic. Here we describe a method ex...
<h3>Introduction</h3> The immediate detection of pathogens in the lungs patients with unexplained pulmonary opacities intensive care unit would represent a significant advance their management. An optical imaging strategy, including endobronchial administration bacterial specific Smartprobes, confer number advantages over conventional techniques such as bronchoalveolar lavage, principally real-time to immediately inform antimicrobial therapy. aims this study were fluorescently label and...
<h3>Background</h3> Acute respiratory distress syndrome (ARDS) remains an often fatal condition without effective pharmacological therapies. Characteristically, a neutrophil-dominant disorder, it is associated with dysregulated inflammatory response and tissue injury. Neutrophil migration into sites controlled by variety of factors; in sterile injury mitochondrial formylated peptides are released following necrotic cell death bind to formyl peptide receptor 1 (FPR1) on neutrophils induce...
ABSTRACT Despite the success of vaccines and selected repurposed treatments, COVID-19 is likely to remain a global health problem further chemotherapeutics are required. Many drugs have progressed rapidly Phase 2 3 trials without characterisation Pharmacokinetics (PK)/Pharmacodynamics (PD) including safety in COVID-19. One such drug Nafamostat Mesylate (Nafamostat), synthetic serine protease inhibitor with anticoagulant anti-inflammatory properties. Preclinical data has demonstrated that it...
Background: Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is Nafamostat Mesylate.Methods: We present the findings a phase Ib/II open label, platform randomised controlled trial intravenous hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly standard care (SoC), or an alternative therapy. was administered as infusion at...