This meeting will be held at The BioPark ,Hertfordshire, UK and has CPD approval.

 The Chair will be Dr Alan Wallace.

 

 The Agenda includes:

 

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.

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.

 

Nitrite: Can we teach an old dog new tricks?  - Dr Alexandra Milsom, Barts & The London Medical School, UK.

 Nitrite has a historical role in areas as diverse as medicine, explosives and food preservation. In medicine recent evidence has shown that the reduction of nitrite via chemical acidification and a nitrite-reductase activity of various endogenous proteins may increase nitric oxide (NO) bioavailability through the nitrate-nitrite-NO pathway. Nitrite reduction to NO is enhanced during hypoxia, a condition under which constitutive NO production in the vasculature may be reduced. Nitrite has been used successfully to protect against ischaemia-induced tissue damage in a number of ischaemia/reperfusion models.  This presentation will discuss the history of nitrite, from an ancient cure for evil to a toxicological bad guy, and its future potential in the treatment of vascular disease and ischaemia/reperfusion injury.

 

Talk title to be confirmed - Professor Joseph Bonaventura , Duke Marine Lab , Duke University,  USA .

 

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. 

 

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.

 

S-Nitrosoglutathione Metabolism  -  Dr Lea-Ann Dailey, King's College, London .

 

Nitric Oxide management strategies in pathogenic enterobacteria  - Dr Gary Rowley.
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

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Nitric oxide in intestinal barrier breakdown leading to colitis - Professor William Roediger, University of Adelaide, Australia.
Excess nitric oxide from anaerobic bacterial denitrification, together with sulphide from anaerobic fermentation of protein, is capable of inactivating free CoA in colonocytes by S-nitrosylation, producing nitrosothiols. Depletion of free CoA diminishes lipid synthesis, detoxification and beta oxidation in colonocytes. In conjunction with impaired protein synthesis by NO, cellular membranes and tight junctions of the colonic epithelial lining cells are impaired which leads to epithelial barrier breakdown. Nitric oxide production in the rectal lumen of ulcerative colitis patients is significantly greater than that observed in healthy patients. Areas of prolonged gut mucosal contact with luminal NO, i.e. distal colon and appendix, are most prone to develop colitis. Free CoA depletion can be established in experimental animals producing a colitis identical to human UC. Therapies to alter bacterial nitrate respiration and NO production in the colon of UC need to be developed in the future

 

If you would like to book a place please visit: www.regonline.co.uk/no09