Dr Ulvi Bayraktutan Faculty of Medicine & Health Sciences Life Sciences Genetics, Immunity and Infections, Cell and Developmental Biology, Microbiology, Neuroscience, Pharmacology and Physiology Health Sciences Nursing, Midwifery, Physiotherapy / Sport Rehabilitation Veterinary Medicine and Science Animal infection/immunity, Comparative Medicine, Reproductive Biology, Population Health and Welfare School of Medicine Cancer and Stem Cells; Child Health, Obstetrics and Gynaecology; Epidemiology and Public Health; Primary Care; Psychiatry and Applied Psychology; Rehabilitation and Ageing; Respiratory Medicine; Rheumatology, Orthopaedics and Dermatology; Clinical Neuroscience (Stroke, Cardiovascular Medicine, Clinical Neurology, Ophthalmology, Anaesthesia and Critical Care, Radiological Sciences, Otology) 2-4 February 2016 MRC-ASM Health Research Workshop, KL, Malaysia 1
GLOBAL RESEARCH THEME: HEALTH & WELLBEING RESEARCH PRIORITY AREAS 1. Antimicrobials and Antimicrobial Resistance 2. Brain Health across the Lifespan 3. Cancer 4. Chronic Inflammatory Disease 5. Healthcare Technologies 6. Musculoskeletal Health in Ageing and Wellbeing 7. Regenerative Medicines and Stem Cells 8. Translational Biomedical Imaging 2
POSSIBLE COLLABORATIVE STUDIES Fiona Broughton-Pipkin (Prof Emeritus of Perinatal Physiology) long-term follow up of women who developed hypertension in pregnancy Fiona.Broughton-Pipkin@nottingham.ac.uk Guru Aithal (Prof of Hepatology) and Michael Symonds (Prof of Developmental Physiology) Role of brown fat function in relation to ethnicity specific genetic and life style factors in a susceptible population in Malaysia Guru.Aithal@nottingham.ac.uk Michael.Symonds@nottingham.ac.uk Maria Toledo-Rodriguez (Assistant Prof, School of Life Sciences) long-term exercise to prevent or treat mental and physical diseases including CVD, obesity and diabetes. Maria.Toledo@nottingham.ac.uk 3
STROKE MEDICINE Clinical studies Phase I, II and III trials in acute stroke, stroke recovery and stroke prevention Acute stroke management: ENOS, BASC, TARDIS, TICH-2, RIGHT, UK co-ordinators EuroHYP-1 Prevention and Recovery: PODCAST, STEMS-3 Stroke unit: >1,200 patients/a year Translational studies Blood-brain barrier integrity and function Roles of ischaemic injury, inflammatory cytokines and hyperglycaemia Novel therapies/therapeutics: PPS, RhoA/ROCK, PKC-α/β, Nox, hypothermia Clinical biomarkers Cardiovascular studies Patency rates of IMA, RA and SV --- Vein graft dysfunction (CV risk factors, ROS) Polymorphisms in IHD: enos (G894T), p22-phox (C242T) Translational studies Langendorff isolated heart system; isometric tension studies; cell culture (CMEC, VSMC) Antioxidants (vitamins, enzymes, ROS scavengers), ARB, diuretics, Endothelial dysfunction key phenomenon in CV disease pathogenesis 4
Aim: novel therapies or therapeutics to influence clinical practice Reason: mortality; morbidity; financial cost; >3,000 clinical trials with no positive results Causes of failure Targeted mechanism Therapeutic window Assessment of outcomes Diversity of stroke types Differences in comorbidities In vitro: hyperglycaemia, OGD±R, inflammation: PKC-α/β, Nox, Ca 2+, upa, RhoA/ROCK In vivo: different disease models e.g. hypertensive, diabetic and aged animals Transwell insert HBMEC Lateral Astrocytes Basolateral Collagen membrane pericytes 5
EXPERIMENTAL GROUP TEER (Ωcm 2 ) NaF (µl) EBA (µl) Control (unscratched) 126±3 vs 129±4 65±6 vs 62±3 39±3 vs 37±4 OECs (3.5x10 4 ) 104±5 * vs 131±3 98±6 * vs 59±4 62±6 * vs 33±3 Early EPCs (3.5x10 4 ) 103±2 * vs 119±4 * 93±5 * vs 78±3 * 64±5 * vs 51±4 * Scratch control 106±4 * vs 115±3 * 94±4 * vs 76±5 * 59±2 * vs 49±3 * OEC vehicle Ipsilateral brain water content 78.5±0.4% vs 82.3±0.4%, n=4, p<0.05 Contralateral brain water content 77.7±0.3% vs 77.8±0.4%, n=4, p>0.05 Project-1: EPCs as clinical biomarkers for ischaemic stroke and its subtypes: investigate the numerical and functional aspects of EPC in stroke patients vs age-matched controls with reference to stroke severity and outcome Project-2: Translational studies to assess the therapeutic capacity of OECs ± a specific inhibitor for PKC-α/β in aged SHR and GK diabetic rats exposed to MCAO or sham operation Project-3: EPCs: in patients with MI and HF Cardiac unit: >4,500 patients (600 MI) ulvi.bayraktutan@nottingham.ac.uk 6