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.

Consultation with an expert rheumatology nurse in a drug monitor clinic may add value in terms of improving patients' perceived ability to cope with the arthritis.

Proton Hahn spin-echo n.m.r. spectroscopy was employed to detect abnormal metabolites present in rheumatoid synovial fluid that are derived from the deleterious generation of reactive oxygen radical species during exercise of the inflamed rheumatoid joint. A resonance attributable to a low-molecular-mass N-acetylglucosamine-containing oligosaccharide formed by the oxygen-radical-mediated depolymerization of synovial-fluid hyaluronate was clearly demonstrable when subjects with inflammatory joint disease were exercised. Moreover, formate, which may be derived from the attack of OH.radical on synovial-fluid carbohydrates, was also readily detectable in these samples. gamma-Radiolysis of rheumatoid synovial fluid samples and aqueous solutions of hyaluronate also gave rise to the production of the low-molecular-mass hyaluronate-derived oligosaccharide species and markedly elevated concentrations of (non-protein-bound) formate in the biological fluids. As expected, corresponding spectra of gamma-irradiated blood serum samples obtained from normal volunteers did not contain the signal attributable to the low-molecular-mass oligosaccharide species, but the formate resonance (barely detectable in non-irradiated normal serum samples) became clearly visible. Additionally, a curious increase in the effective concentration of non-protein-bound low-molecular-mass metabolites such as acetate, citrate, lactate and glutamine was observed after gamma-radiolysis of all biological fluids studied. The hyaluronate-derived low-molecular-mass oligosaccharide species and formate are suggested as novel markers of reactive oxygen radical activity in the inflamed rheumatoid joint during exercise-induced hypoxic/reperfusion injury.

30 patients with supraspinatus or bicipital tendonitis were randomly allocated to active infrared laser therapy at 904 nm three times weekly for 2 weeks, dummy laser or drug treatment for 2 weeks. Objectively maximum active extension, flexion and abduction of the shoulder, and subjectively pain stiffness movement and function were measured at 0 and 2 weeks. Significant improvement of active over dummy laser was noted for all seven assessments. Active laser therapy produced significant improvement over drug therapy for all three objective measures and pain. Naproxen sodium significantly improved only movement and function compared to dummy laser. These results demonstrate the effectiveness of laser therapy in tendonitis of the shoulder.

In recent years considerable research interest has been directed at studying the biological consequences of tissue hypoxia. As this work progresses it becomes increasingly apparent that tissue hypoxia has complex biological consequences. Much is now known about the natural defences of the body to hypoxia, including heat shock protein synthesis and angiogenesis. These systems are normally under rigid control, but this would seem not so in the rheumatoid joint. This accumulation of knowledge has prompted the belated reawakening of interest in joint hypoxia; it is now clear that an understanding of the physiological and pathological effects of joint hypoxia is of great importance to both clinical and research rheumatology.This review outlines joint hypoxia from a historical perspective and offers explanations for the phenomenon. Some of the more pertinent implications of hypoxia in the context of inflammatory synovitis are discussed.

Nitric oxide is a gas generally known by its chemical formula NO, or NO. The dot denotes an unpaired electron, which is the definition of a free radical; pbssessing this, NO is highly reactive and quite -different from the anaesthetic agent nitrous oxide (N20), which is extremely stable. Until recently, NO was best known as a constituent of car exhaust fumes, contributing to the photochemical smog of cities such as Los Angeles. In contrast, the work which crucially altered this perception was performed in a leafy Kentish suburb at the Wellcome Foundation in Beckenham, UK. In 1987, it was shown that NO was the long sought endothelium derived relaxing factor (EDRF).' This was a crucial discovery for cardiovascular biology, and it soon became evident that NO was produced by many cell types and performed diverse functions, including inhibition of platelet aggregation and mediation of the cytotoxic action of activated macrophages, and had a role in central and peripheral neurotransmission.NO is enzymically synthesised from L-arginine by oxidation of one of the terminal guanidino nitrogen atoms of L-arginine,2-a process inhibited by L-arginine analogues such as N0-monomethyl-L-arginine (LNMMA).

The proteinase inhibitory ability of a, antitrypsin was measured in 23 samples of rheumatoid arthritis synovial fluid, eight osteoarthritic synovial fluids and nine normal control serum samples. For each sample a detailed kinetic analysis was performed with porcine pancreatic elastase as the target proteinase. Samples were stored for less than 24 hours at 4°C before analysis, which does not significantly alter the proportion of inactive a, antitrypsin. In rheumatoid synovial fluid the elastase inhibitory ability was disproportionately depressed relative to the immunochemically determined concentrations of a, antitrypsin. Results and discussionNormal serum contained 3-74 (1-50) (mean (SD)) mg/ml a, antitrypsin. As expected, the 915 on 30 April 2019 by guest. Protected by copyright.

Hyaluronan (hyaluronic acid, hyaluronate, see ref 1 for discussion of current nomenclature) is a linear repeating disaccharide, P-D-glucuronylf3-D-N-acetylglucosamine, of high molecular weight (upwards of 10 000 000 daltons). It is almost ubiquitous in its distribution, being present in the interstitial spaces on most animal tissues.2 Hyaluronan also forms the central axis of the proteoglycan aggregates necessary for the functional integrity of articular cartilage and other extracellular matrices.3In its unaggregated form hyaluronan is secreted continuously into the joint space by elements of the synovium, though some contribution may be made by the chondrocyte. The apparent decrease in the weight average molecular mass of synovial hyaluronan in these patients may be explained in two ways: either by defective synthesis with premature termination of the nascent polysaccharide chain, or by fragmentation of the intact chain after secretion into the synovial cavity. Recent pulsechase experiments have supported the view that the presence of short chain molecules of hyaluronan in arthritic synovial fluid is due to degradation after synthesis rather than to defective synthesis.'7 As normal and inflammatory synovial fluids contain no hyaluronidase activity it has been inferred for some time that reactive oxygen derived radical species (RORS) cause hyaluronan depolymerisation. 820 Broadly, the evidence derives from two approaches: (a) the demonstration of potential free radical generating systems within the joint and (b) the demonstration of hyaluronan degradation by such systems in vitro as shown by decreased viscometric parameters and apparent hyaluronan molecular mass when measured by gel filtration.