A5067199485- Organ Transplantation Techniques and Outcomes
- Renal Transplantation Outcomes and Treatments
- Organ Donation and Transplantation
- Liver Disease and Transplantation
- Cardiac Ischemia and Reperfusion
- Redox biology and oxidative stress
- Sulfur Compounds in Biology
- Transplantation: Methods and Outcomes
- Acute Kidney Injury Research
- Metabolism and Genetic Disorders
- Tissue Engineering and Regenerative Medicine
- Eicosanoids and Hypertension Pharmacology
- Renal and Vascular Pathologies
- Nitric Oxide and Endothelin Effects
- Metabolomics and Mass Spectrometry Studies
- Heat shock proteins research
- Spectroscopy and Quantum Chemical Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Asthma and respiratory diseases
- Advanced Proteomics Techniques and Applications
- Sexual Differentiation and Disorders
- Neuroscience of respiration and sleep
- Quality Function Deployment in Product Design
- Ammonia Synthesis and Nitrogen Reduction
- Vitamin D Research Studies
University of Oxford
2015-2025
Oxford BioMedica (United Kingdom)
2020-2024
Nuffield Orthopaedic Centre
2018-2022
Churchill Hospital
2014-2020
Oxford Biomedical Research
2020
National Heart Institute
2019
University of Exeter
2010-2014
Peninsula College of Medicine and Dentistry
2010
University of Catania
2009
Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ use, and improved transplant logistics. Eleven clinically declined kidneys were perfused normothermically, with 6 being from donors after brain death (median cold ischemia time 33 ± 36.9 hours) 5 circulatory (36.2 38.3 hours). Three using Ringer's lactate to replace excreted urine volume, 8 recirculation maintain perfusate volume without fluid...
J-Aggregate antworten dynamisch auf durch Rühren erzeugte Strudel. Das CD-Signal kehrt sich mit der Rührrichtung um, und seine Intensität nimmt zu. Bei längerem lagern chirale Aggregate an Küvettenwand ab, deren Chiraliät von abhängt. verschiebt das Gleichgewicht einer racemischen Mischung zu die gewählten (und bevorzugten) Seite (siehe Bild; CW,CCW: im bzw. gegen den Uhrzeiger). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents...
Ischaemia and reperfusion injury (IRI) is the leading cause of acute kidney (AKI), which contributes to high morbidity mortality rates in a wide range injuries as well development chronic disease. The cellular molecular responses IRI are complex not fully understood. Here, we used an integrated proteomic metabolomic approach investigate effects on protein abundance metabolite levels. Rat kidneys were subjected 45 min warm ischaemia followed by 4 h 24 reperfusion, with contralateral separate...
Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti-inflammatory effects in ischemia-reperfusion injury. The aims this study were evaluate safety feasibility MSC treatment during NMP using a porcine autotransplantation model, examine potential treatment-associated kidney improvements up 14 days posttransplant. After 75 min warm...
Abstract Introduction Ischaemia-reperfusion injury (IRI) is inevitable in transplantation. Necroptosis a form of cell death kidney IRI and phosphorylation RIPK1 plays key role this pathway. This study investigated the effectiveness delivering GNE684 -a kinase inhibitor- during static cold storage (SCS) hypothermic machine perfusion (HMP) an ex-vivo model IRI. Methods Pig kidneys underwent 1h warm ischaemia were retrieved. In SCS model, pairs (n=6) randomised to treatment with UW+GNE684 via...
Abstract Introduction Normothermic machine perfusion of the kidney (NMP-K) is a technique for ex-situ preservation, assessment, and treatment kidneys prior to transplantation. We have previously reported phase 1 trial (NKP1) showing that up 24 hours NMP-K appears be safe, feasible, NRF-2 modulation may benefit. Nitric oxide (NO) potent inducer NRF2 has been shown halve rate acute injury after cardiopulmonary bypass. therefore sought develop test paradigm NO during NMP-K. Methods Six pairs...
Peroxiredoxin 2 has immune regulatory functions, but its expression in human peripheral blood lymphocytes and levels extracellular fluid healthy subjects rheumatoid arthritis patients are poorly described. In the present study, median intracellular peroxiredoxin protein content of from was more than two-fold higher compared with subjects' lymphocytes. Intracellular 3 were similar Flow cytometry detected on surface ca. 8% T cells 56% B (median % values) all analyzed. Exofacial thioredoxin-1...
We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and replacement (UR). Proteins were extracted from 16 kidney biopsies URC (n = 8 donors after brain death [DBD], n circulatory [DCD]) three UR 2 DBD, 1 DCD), followed by quantitative mass spectrometry. Damage-associated patterns (DAMPs) decreased in tissue 6 hours NMP URC, suggesting reduced inflammation....
IntroductionDelayed graft function (DGF) is often defined as the need for dialysis treatment in first week after a kidney transplantation. This definition, though readily applicable, generic and unable to distinguish between "types" of DGF or time needed recover that may also significantly affect longer-term outcomes. We aimed profile biological pathways DCD donors correlate with different durations.MethodsN=30 biopsies were selected from UK Quality Organ Donation biobank stratified...
In an era where we are becoming more reliant on vulnerable kidneys for transplantation from older donors, there is urgent need to understand how brain death leads kidney dysfunction and, hence, this can be prevented. Using a rodent model of hemorrhagic stroke and next-generation proteomic metabolomic technologies, aimed delineate which key cellular processes perturbed in the after death. Pathway analysis signature brain-dead donors revealed large-scale changes mitochondrial proteins that...
Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) utilized clinically other organs assess viability. Our aim was develop NR using normothermic machine perfusion technique simulate at time of transplantation, enabling evaluation oxygenated hypothermic (HMPO2) as a newer strategy optimize preservation. 13 porcine pancreases procured after circulatory death were divided...
The organ perfusion solution (perfusate), collected at clinically and temporally significant stages of the preservation transplantation process, provides a valuable insight into biological status an over time prior to reperfusion (transplantation) in recipient. objective this study was assess two bottom-up proteomics workflows for extraction tryptic peptides from perfusate.Two different kinds perfusate samples kidney liver trials were profiled using liquid chromatography-mass spectrometry...
Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of kidney has been studied extensively during last two decades and implemented in clinical trials. Biomarker research led to success identifying molecules diagnostic, predictive therapeutic properties chronic However, perfusate biomarkers potential mechanisms NMP have not identified yet. Twelve discarded human kidneys ( n = 7 DBD, 5 DCD)...
Ischaemia-reperfusion injury (IRI) is an inevitable process in transplantation and results inflammation immune system activation. Alpha-1 antitrypsin (AAT) has anti-inflammatory properties. Normothermic machine perfusion (NMP) can be used to deliver therapies may help assessing the effects of IRI immunity. This study investigated AAT on pig kidneys when administered during preservation, followed by normothermic reperfusion (NR) with autologous whole blood, as a surrogate for transplant. Two...
Donor kidney assessment may improve organ utilisation. Normothermic Machine Perfusion (NMP) has the potential to facilitate this advance. The mechanism of action is not yet determined and we aimed assess mitochondrial function during NMP. Anaesthetised pigs ( n = 6) had one clamped for 60 min. healthy contralateral was removed underwent NMP 8 h (healthy control (HC), 6). Following min warm ischaemia injured HMP 24 h, followed by Mitochondria were extracted from fresh tissue analysis. Injured...
Abstract The utilization of kidneys from donors with acute kidney injury (AKI) is often limited by unpredictable post-transplantation outcomes. aim our study was to identify protein mediators implicated in either recovery or failure these organs. Forty biopsies (20) and without AKI were selected then subdivided according the post-transplant outcome defined as a threshold 45 ml/min for eGFR at 1 year transplantation. Tissue homogenates analysed western blot assess how levels 17 pre-selected...
Static Cold Storage (SCS) injures the bile duct, while effect of Normothermic Machine Perfusion (NMP) is unknown. In a sub-study COPE trial on liver NMP, we investigated impact preservation type histological duct injury score (BDIS). Transplants with at least one biopsy, either end or 1 h post-reperfusion, were considered. BDIS was determined by assessing peribiliary glands injury, stromal and mural loss, haemorrhage, thrombosis. A bivariate linear model compared (estimate, CI) between...
Abstract Pancreatic static cold storage (SCS) is the gold‐standard method for pancreas preservation. Our main objective was to evaluate feasibility of hypothermic perfusion (HP) nonhuman primates’ pancreases potential organ transplantation. Seven baboon were tested. Animals included in a study approved by French Research Ministry Health. Two groups compared: control group (n = 2) preserved using conventional SCS 24‐h and 5) used HP 24‐h, with three different pressures (PP): 15 3), 20 1), 25...
To provide mechanistic insight into key biological alterations in donation after circulatory death kidneys during continuous pefusion we performed mass spectrometry profiling of perfusate samples collected a phase 3 randomized double-blind paired clinical trial hypothermic machine perfusion with and without oxygen (COMPARE).Despite the benefits novel technologies aiming to better preserve donor organs, processes that may be altered have remained largely unexplored. The collection serial...