Rheumatoid Arthritis: Lucacchini A

Baldini C, Giusti L, Bazzichi L, Lucacchini A, Bombardieri S. · Department of Internal Medicine, Rheumatology Unit, University of Pisa, Via Roma 67, 56126 Pisa, Italy. · Autoimmun Rev. · Pubmed #18190876 No free full text.

Abstract: The clinical entity of secondary Sjögren's syndrome (SS) is controversial and the relationship with primary SS and other systemic autoimmune diseases is still far from being completely understood. In the last few years, proteomic approaches have been applied with a growing interest in the search for diagnostic biomarkers for many rheumatic diseases and it is possible that, in the near future, proteomic analysis of human saliva could help in distinguishing also primary from secondary SS. This review summarizes the state of the art of proteomic analysis of human saliva in the diagnosis of connective diseases focusing its advantages, limits and future perspectives.

Giusti L, Baldini C, Bazzichi L, Bombardieri S, Lucacchini A. · University of Pisa, Department of Psychiatry, Neurobiology, Pharmacology & Biotechnology, Via Bonanno 6, 56126 Pisa, Italy. · Expert Rev Proteomics. · Pubmed #18067414 No free full text.

Abstract: In the last few years, a growing interest has arisen in the application of proteomic analysis to rheumatic disease. Sjögren's syndrome is a systemic disease that affects exocrine glands directly, and is therefore expected to influence the composition of the whole human saliva and lachrymal fluid. Therefore, a rising number of studies have been performed in an attempt to characterize the salivary and lachrymal protein profiles of patients with Sjögren's syndrome by using a proteomic approach. This review summarizes the state of the art and the potential application of proteomics in the systematic search for diagnostic biomarkers in Sjögren's syndrome.

Giusti L, Baldini C, Bazzichi L, Ciregia F, Tonazzini I, Mascia G, Giannaccini G, Bombardieri S, Lucacchini A. · Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy. · Proteomics. · Pubmed #17436266 No free full text.

Abstract: Sjögren's syndrome (pSS) is a systemic disease that affects salivary glands directly, and is therefore expected to influence the composition of human whole saliva (WS) fluid. The aim of this study was to characterize the WS proteins of pSS patients using a proteomic approach to assess a valid procedure to examine the global changes of the salivary protein profiles in connective tissue disorders. The WS proteins expressed in patients affected by pSS and healthy volunteers were analyzed using the 2-DE technique. The WS protein pattern was altered in pSS patients compared to controls, with a decrease in some of the typical salivary proteins. Particularly, a remarkable alteration of carbonic anhydrase VI was observed. Moreover, a comparison of WS protein profile of pSS patients with the one obtained from controls revealed a set of differentially expressed proteins. These proteins were related to acute and chronic inflammation while some others were involved in oxidative stress injury. These findings are in line with the systemic immuno-inflammatory aspects of pSS and open the possibility for a systematic search of diagnostic biomarkers and targets for therapeutic intervention in pSS.

Giusti L, Betti L, Giannaccini G, Mascia G, Bazzichi L, Lucacchini A. · Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy. · Clin Biochem. · Pubmed #14675564 No free full text.

Abstract: OBJECTIVE: The objectives of this study were to evaluate the [3H]PK11195 binding parameters in a model of acute inflammation, the N-formylmethionine-leucine-phenylalanine (fMLP)-stimulated neutrophil cell membranes, and to analyze if alterations of peripheral-type benzodiazepine receptor (PBR) characteristics occurred in neutrophil cell membranes of patients affected by osteoarthritis (OA), rheumatoid arthritis (RA), and psoriasic arthritis (PA). DESIGN AND METHODS: Neutrophils were obtained from 15 patients with OA, 15 patients with RA, and 15 patients with PA. fMLP stimulation was performed to aliquots of neutrophils from six healthy individuals. Evaluation of kinetic parameters of PBR was performed using [3H]PK11195, as specific radioligand compared with 15 healthy volunteers. RESULTS: The results showed a significant decrease of Kd and Bmax in fMLP-stimulated neutrophil membranes. Moreover, an increase of PBR binding sites and affinity value was observed in neutrophils membranes from PA patients. CONCLUSIONS: Our data suggested a fMLP modulation on [3H]PK11195 binding in human neutrophils. Moreover, our results showed an up-regulation of PBR in neutrophils of PA patients.

Bazzichi L, Betti L, Giannaccini G, Rossi A, Lucacchini A. · Rheumatic Diseases Unit, Medica Santa Chiara Hospital, University of Pisa, Italy. · Clin Biochem. · Pubmed #12554061 No free full text.

Abstract: OBJECTIVES: The objective of this study was to evaluate the kinetic parameters at equilibrium of peripheral benzodiazepine receptors (PBR) in human mononuclear cells from patients affected by osteoarthritis (OA), rheumatoid arthritis (RA) and psoriasic arthritis (PA). DESIGN AND METHODS: Mononuclear cells were obtained from 10 patients with OA, 10 patients with RA and 10 patients with PA. Evaluation of kinetic parameters of PBR was performed using [(3)H]PK 11195, a specific radioligand for this receptor, and compared with 10 healthy controls. RESULTS: The results show a statistically significant decrease (37.5%, as an absolute percentage) in the maximal number of binding sites (B(max)) of patients with OA, compared with healthy controls; however, the values of the dissociation constant (K(d)) at equilibrium do not show any statistically significant variations. CONCLUSIONS: These data further confirm the presence of peripheral biochemical alterations in OA. As peripheral benzodiazepine receptors appear to be involved in the immune function, and in the protection of hematopoietic cells against oxygen radical damage, the observed decrease in B(max) might be related to cellular protection.

Bazzichi L, Ciompi ML, Betti L, Rossi A, Melchiorre D, Fiorini M, Giannaccini G, Lucacchini A. · Rheumatic Diseases Unit, Medica Santa Chiara Hospital, University of Pisa, Pisa, Italy. · Clin Exp Rheumatol. · Pubmed #12508766 No free full text.

Abstract: OBJECTIVE: To test the activity of elastase, collagenase and glutathione reductase in the synovial fluid (SF) of patients with rheumatoid arthritis (RA) and in patients with osteoarthritis (OA); to correlate the elastase and collagenase activity with the glutathione reductase activity, which is important for the inactivation of oxygen free radicals. METHODS: 24 patients affected by osteoarthrosis and 24 patients affected by rheumatoid arthritis took part in the study. We measured elastase activity towards the substrate metoxysuccinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide (MeOSuc-ala-ala-proval-p-NA) which is highly specific for elastase, and insensitive to the other serine proteases, such as cathepsin G; collagenase activity was measured using [14C]-acetylated collagen as the substrate. Glutathione reductase activity was measured following the oxidation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) in the presence of oxidized glutathione (GSSG). RESULTS: The concentrations of elastase, collagenase and glutathione reductase were statistically higher in patients with RA than in patients with OA. Moreover, in the SF of patients with RA we found positive correlation between enzyme activity levels. CONCLUSION: These results confirm a high activity of collagenase and elastase in the SF of patients with RA, which is about 30 times higher than that found in the SF of patients with OA. These data underline the synergic action of these enzymes in the pathogenesis of joint damage. RA patients also exhibit higher levels of glutathione reductase, which is important for the detoxification pathway of oxygen free radicals. However, compared with findings for collagenase and elastase, the increase in glutathione reductase is only three times higher than level found in the SF of OA patients. The limited increase in glutathione reductase activity during the inflammatory process might lead to an insufficient protective effect at the joint level in rheumatoid arthritis.