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Cytokines induce nitric oxide synthesis by endothelial ceils, macrophages and polymorphonuclear leucocytes, indicating a role for nitric oxide in inflammatory processes. Nitric oxide production was therefore measured indirectly as nitrite in serum and synovial fluid samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) together with serum samples from healthy volunteers matched for age and sex. Serum nitrite concentrations in patients with RA and OA were significantly higher than in controls. In both disease groups synovial fluid nitrite was significantly higher than serum nitrite, implying nitric oxide synthesis by the synovium. Serum and synovial fluid nitrite concentrations in RA were also significantly higher than those in OA. These data show increased nitric oxide production in RA and OA and suggest a role for nitric oxide as an inflammatory mediator in rheumatic diseases.

Xanthine oxidoreductase (XOR) catalyses the reduction of the therapeutic organic nitrate, nitroglycerin (glyceryl trinitrate, GTN), as well as inorganic nitrate and nitrite, to nitric oxide (NO) under hypoxic conditions in the presence of NADH. Generation of nitric oxide is not detectable under normoxic conditions and is inhibited by the molybdenum site-specific inhibitors, oxypurinol and (3)BOF 4272. These enzymic reactions provide a mechanism for generation of NO under hypoxic conditions where nitric oxide synthase does not function, suggesting a vasodilatory role in ischaemia.z 1998 Federation of European Biochemical Societies.

Xanthine oxidase (XO) was shown to catalyze the reduction of nitrite to nitric oxide (NO), under anaerobic conditions, in the presence of either NADH or xanthine as reducing substrate. NO production was directly demonstrated by ozone chemiluminescence and showed stoichiometry of approximately 2:1 versus NADH depletion. With xanthine as reducing substrate, the kinetics of NO production were complicated by enzyme inactivation, resulting from NO-induced conversion of XO to its relatively inactive desulfo-form. Steady-state kinetic parameters were determined spectrophotometrically for urate production and NADH oxidation catalyzed by XO and xanthine dehydrogenase in the presence of nitrite under anaerobic conditions. pH optima for anaerobic NO production catalyzed by XO in the presence of nitrite were 7.0 for NADH and <6.0 for xanthine. Involvement of the molybdenum site of XO in nitrite reduction was shown by the fact that alloxanthine inhibits xanthine oxidation competitively with nitrite. Strong preference for Mo‫؍‬S over Mo‫؍‬O was shown by the relatively very low NADH-nitrite reductase activity shown by desulfo-enzyme. The FAD site of XO was shown not to influence nitrite reduction in the presence of xanthine, although it was clearly involved when NADH was the reducing substrate. Apparent production of NO decreased with increasing oxygen tensions, consistent with reaction of NO with XO-generated superoxide. It is proposed that XO-derived NO fulfills a bactericidal role in the digestive tract.

In early CRPS (type 1), visual input from a moving, unaffected limb re-establishes the pain-free relationship between sensory feedback and motor execution. Trophic changes and a less plastic neural pathway preclude this in chronic disease.

12 Abstract 13In spite of pain in the CRPS limb, clinical observations show patients pay little attention to, and fail to care for, their affected 14 limb as if it were not part of their body. Literature describes this phenomenon in terms of neurological neglect-like symptoms. This 15 qualitative study sought to explore the nature of this phenomenon with a view to providing insights into central mechanisms and the 16 relationship with pain. Twenty-seven participants who met the IASP CRPS classification were interviewed using qualitative methods 17 to explore feelings and perceptions about their affected body parts. These semi-structured interviews were analysed utilising princi-18 ples of grounded theory. Participants revealed bizarre perceptions about a part of their body and expressed a desperate desire to 19 amputate this part despite the prospect of further pain and functional loss. A mismatch was experienced between the sensation 20 of the limb and how it looked. Anatomical parts of the CRPS limb were erased in mental representations of the affected area. Pain 21 generated a raised consciousness of the limb yet there was a lack of awareness as to its position. These feelings were about the CRPS 22 limb only as the remaining unaffected body was felt to be normal. Findings suggest that there is a complex interaction between pain, 23 disturbances in body perception and central remapping. Clinically, findings support the use of treatments that target cortical areas, 24 which may reduce body perception disturbance and pain. We propose that body perception disturbance is a more appropriate term 25 than 'neglect-like' symptoms to describe this phenomenon. 26

To determine if reactive oxygen metabolites have a pathogenic role in Helicobacter pylon (H pylon) related gastroduodenal disease, this study measured their production in antral mucosal biopsy specimens. Two related chemiluminescence techniques were used comparing H pylon positive (n=105) and negative patients (n=64) with a similar spectrum of macroscopic disease. After chemiluminescence assays, biopsy specimens were graded histologically. Increased luminol dependent chemiluminescence (detecting reactive oxygen metabolites through peroxidase catalysed reactions) was found in H pylon positive patients (median photon emission=6*4X 103/min/mg wet weight (95% confidence intervals 3-6 to 9.9)) but not H pylori negative cases (-0.9 (-1.3 to -0.6))

In the first ever controlled trial of a CBM in RA, a significant analgesic effect was observed and disease activity was significantly suppressed following Sativex treatment. Whilst the differences are small and variable across the population, they represent benefits of clinical relevance and show the need for more detailed investigation in this indication.