BioPark Hertfordshire, Welwyn Garden City
March 20th 2009
9:00 – 9:45 Registration 9:45 – 10:00 Introduction by the Chair: Dr Alan Wallace 10:00 – 10:30 The nitrate-nitrite-NO pathway in health and disease Dr Jon Lundberg, Karolinska, Sweden Nitric oxide (NO) is generally viewed as an autocrine or paracrine messenger, mostly regulating local intracellular processes or acting on cells in its near vicinity. The major metabolic pathway for NO involves its rapid oxidation into the higher nitrogen oxides nitrite and nitrate. Until recently, these inorganic anions have been generally considered to be inert endproducts of NO metabolism. Although, it is true that the bioactivity of NO is acutely terminated following oxidation to nitrate and nitrite, recent lines of research now suggest that a reverse pathway exists in which nitrate and nitrite are reduced stepwise into bioactive NO again. The nitrate-nitrite-NO pathway is emerging as a likely regulator of physiological functions in the gastrointestinal tract and in the cardiovascular system. In particular, it might serve as a backup system to ensure NO like bioactivity also in situations when the endogenous L-arginine/NO synthase pathway is dysfunctional. In addition, this alternative pathway can be harnessed therapeutically in prevention and treatment of disease. Finally, there is an intriguing nutritional aspect to this, since the major supply of nitrate and nitrite in our bodies comes from our everyday diet. 10:30 – 11:00 Targeting eNOS coupling in human atherosclerosis Dr. Charalambos Antoniades, University of Athens and University of Oxford-UK Endothelial nitric oxide synthase (eNOS), maintains its enzymatic coupling in the presence of its co-factor tetrahydrobiopterin (BH4). Under conditions of increased oxidative stress, BH4 may be oxidized leading to eNOS uncoupling. The uncoupled form of eNOS then becomes a source of superoxide radicals instead of NO. Strategies targeting eNOS coupling are usually focused on increasing BH4 bioavailability, either by increasing its synthesis or by preventing its oxidation. These strategies include antioxidants and especially the administration of 5-methyl-tetrahydrofolate, as well as direct exogenous BH4 administration. The impact of routinely used therapeutic strategies in human atherosclerosis such as statins, needs further investigation 11:00- 11:05 Speakers photo 11:05 – 11:30 Mid-morning break 11:30 – 12:00 Nitrite: Can we teach an old dog new tricks? Dr Alexandra Milsom, Barts & The London Medical School, UK. 12:00 – 12:30 Talk title to be confirmed Prof essorJoseph Bonaventura , Duke Marine Lab , Duke University, USA
12:30 – 12:40 Introduction to the Biopark 12:40 – 13:30 Lunch and Poster Viewing 13:30 – 14:00 Nitric oxide in the life and death of neuronal cells Dr Guy Brown, Department of Biochemistry, University of Cambridge, UK High levels of NO can be produced by inducible NO synthase expressed in glial cells in inflammatory conditions. But in addition to iNOS expression, NO-induced neuronal death normally requires either (i) hypoxia to enable NO to inhibit mitochondrial respiration, or (ii) superoxide production from microglial NADPH oxidase, reacting with NO to give neurotoxic peroxynitrite. 14:00 – 14:30 The where, why and how of targeted nitric oxide delivery Professor Ian Megson, UHi Millenium Institute, Inverness Since its discovery in the 1980s, nitric oxide (NO) has been heralded as a major breakthrough in disease prevention and management. However, the promise and expectations have not yet been delivered with respect to new NO donor drugs on the market and we are still heavily reliant on drugs that have been in use for decades. One possible reason for the lack of development in this area is the lack of specificity of many NO donor drugs and their global impact, as opposed to local activity. This presentation will explore some possible solutions to tackle targeted NO delivery for use in a number of cardiovascular conditions and will highlight the enormity of the task ahead to fully exploit the remarkable potential of NO in health and disease. 14:30 – 15:00 S-Nitrosoglutathione Metabolism Dr Lea-Ann Dailey, King's College, London
15:00 – 15:30 Afternoon Tea/Coffee and Last Poster Viewing
15:30 - 16:00 Nitric Oxide management strategies in pathogenic enterobacteria Professor David Richardson Nitric oxide (NO) is a highly reactive gas encountered by microbes in many environments. Some bacteria can synthesise NO themselves during cellular respiration in anaerobic conditions. Others meet it within animal tissues where macrophage cells use NO as a toxic molecule to repel the invaders. For every natural toxin, some bacteria have evolved methods to counter the effects. NO is no exception. Salmonella are able to survive and even grow and divide within macrophages. They have at least three enzymes that can metabolise NO. The advantage to the bacterium of multiple methods to counteract one toxic molecule is to give flexibility in the many environments in which the bacteria may find themselves exposed to this gas - in soil, the gastrointestinal tract, the bloodstream or the macrophage, both with and without oxygen . 16:00 – 16:30 Selected oral presentations
16:30 – 17:00 Hydrogen sulfide and the nitric oxide cross-talk: A promising future for two old gas bags? Dr Matt Whitemann, Peninsula Medical School
18:00 Chairman’s summing up followed by… Soiree at *The Best Western Homestead Court Hotel for all the participants
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