Rheumatoid Arthritis: Schiller J

Volpi N, Schiller J, Stern R, Soltés L. · Department of Biologia Animale, University of Modena & Reggio Emilia, Via Campi 213/d, I-41100 Modena, Italy. · Curr Med Chem. · Pubmed #19442142 No free full text.

Abstract: Hyaluronan (hyaluronic acid, HA) is a linear naturally occurring polysaccharide formed from repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronate. Despite its relatively simple structure, HA is an extraordinarily versatile glycosaminoglycan currently receiving attention across a wide front of research areas. It has a very high molar mass, usually in the order of millions of Daltons, and possesses interesting visco-elastic properties based on its polymeric and polyelectrolyte characteristics. HA is omnipresent in the human body and in other vertebrates, occurring in almost all biological fluids and tissues, although the highest amounts of HA are found in the extracellular matrix of soft connective tissues. HA is involved in several key processes, including cell signaling, wound repair and regeneration, morphogenesis, matrix organization and pathobiology. Clinically, it is used as a diagnostic marker for many disease states including cancer, rheumatoid arthritis, liver pathologies, and as an early marker for impending rejection following organ transplantation. It is also used for supplementation of impaired synovial fluid in arthritic patients, following cataract surgery, as a filler in cosmetic and soft tissue surgery, as a device in several surgical procedures, particularly as an anti-adhesive following abdominal procedures, and also in tissue engineering. This review will provide an overview of the structure and physiological role of HA, as well as of its biomedical and industrial applications. Recent advances in biotechnological approaches for the preparation of HA-based materials, and as a component of tissue scaffolding for artificial organs will also be presented.

Fuchs B, Schiller J, Wagner U, Häntzschel H, Arnold K. · Institute of Medical Physics and Biophysics, Medical Department, University of Leipzig, Härtelstr. 16/18, D-04107 Leipzig, Germany. · Clin Biochem. · Pubmed #16043165 No free full text.

Abstract: OBJECTIVES: Lipid second messengers, e.g. lysophosphatidylcholines (LPC) are involved in the pathogenesis of inflammatory diseases, for instance, rheumatoid arthritis (RA). Unfortunately, the analysis of LPC in complex mixtures as present in body fluids is still challenging. DESIGN AND METHODS: Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for phospholipid (PL) analysis of organic extracts of synovial fluids from patients with RA as well as the corresponding plasma. These data were compared with results obtained by high resolution 31P NMR spectroscopy. RESULTS: Synovial fluids may be replaced by plasma since the analysis of both body fluids gives very similar results. Patients undergoing treatment with TNF-alpha inhibitors (ADALIMUMAB (HUMIRA)) were examined in order to investigate whether the clinically-significant attenuation of disease activity is accompanied by changes of the PL composition of plasma. It will be shown that especially the PC/LPC ratios of plasma represent a reliable measure of inflammation and increase upon therapy. CONCLUSIONS: Since plasma samples are readily available, our approach might be useful to draw conclusions before puncture of the affected joints is necessary and the PC/LPC ratio detected in plasma may serve as an indicator of RA in early stages.

Schiller J, Benard S, Reichl S, Arnhold J, Arnold K. · Institute of Medical Physics and Biophysics, Medical Department, University of Leipzig, Germany. · Chem Biol. · Pubmed #11048947 No free full text.

Abstract: BACKGROUND: Although neutrophilic granulocytes clearly contribute to cartilage degradation in rheumatic diseases, it is unclear if reactive oxygen species (ROS) or proteolytic enzymes are the most important components in cartilage degradation and how they interact. RESULTS: Neutrophils were stimulated by chemicals conferring a different degree of ROS formation and enzyme release. Supernatants of neutrophils were incubated with thin slices of pig articular cartilage. Supernatants of cartilage were assayed by NMR spectroscopy, MALDI-TOF mass spectrometry and relevant biochemical methods. Stimulation conditions of neutrophils correlated well with the extent of cartilage degradation. Due to the release of different enzymes, cartilage degradation could be best monitored by NMR since mainly low-mass degradation products were formed. Astonishingly, the suppression of the formation of ROS resulted in decreased cartilage degradation. CONCLUSION: ROS formed by neutrophils are not directly involved in cartilage degradation but influence the activity of proteolytic enzymes, which are the main effectors of cartilage degradation.