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Biomedical subjects

S Antonaci

Publications and source records attributed to S Antonaci.

132 records · Page 8Linked to original sources
PubMedDate not supplied

MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in patients with rheumatoid arthritis and psoriatic arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) and psoriatic arthritis (PA) are both chronic rheumatic inflammatory diseases characterized by disruption of the extra-cellular matrix (ECM) protein of the cartilage, likely induced by proteolytic enzymes such as matrix metalloproteases (MMPs). The goal of this study was to quantify the expression of MMPs such as MMP-2 and MMP-9, and their physiological tissue inhibitors TIMP-2 and TIMP-1, respectively, in serum and synovial fluid. METHODS: Serum and synovial fluid from 24 RA patients and 17 PA patients were studied to determine the levels of MMP-2 and MMP-9 proteolytic activity using a modified gelatin zymography procedure. TIMP-1 and TIMP-2 were measured by a commercially available ELISA kit. RESULTS: Our results show that MMP-2 was detected in the latent form only, while MMP-9 was present in latent and active form. Both gelatinases were more concentrated in synovial fluid than in serum, and TIMP-1 and TIMP-2 concentrations were also more elevated in synovial fluid than in serum. CONCLUSIONS: To investigate the remodelling of cartilage ECM proteins, the evaluation of synovial fluid concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 is more reliable than that determined in serum. In view of these data, MMPs inhibitors might represent a possible target for new therapies delivered directly in the joint space.

Adult↗
PubMedDate not supplied

Infliximab therapy does not modify MMP-2 and MMP-9 serum concentrations in chronic arthritis.

OBJECTIVE: Matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) play a key role in tissue remodelling after processes such as joint destruction in rheumatoid arthritis. Their expression may reflect the disease activity and they could therefore represent a useful marker to assess the efficacy of therapy. In this study MMP-2 and MMP-9 serum were evaluated in patients with chronic arthritis during therapy with the anti-TNFalpha mAb, infliximab. METHODS: Fifty patients with chronic arthritis, 26 with rheumatoid arthritis and 24 with undifferentiated chronic arthritis, were recruited and treated with infliximab (3 mg/kg). Serum concentrations of MMP-2 and MMP-9 were serially measured by gelatine zymography at baseline and after two and fourteen weeks of infliximab therapy. DAS-28 and ACR response criteria were applied to assess disease activity and clinical improvement. Twenty-four healthy donors were included in the study as controls. RESULTS: Although therapy with infliximab induced a statistically significant reduction of the DAS-28 score and improvement of the ACR clinical response, MMP-2 and MMP-9 serum concentrations were not modulated during therapy with infliximab. CONCLUSIONS: Our study provides further evidence that blocking TNFalpha by infliximab is a powerful tool in the management of chronic arthritis. Nevertheless, infliximab does not seem to be able to modify the serum expression of MMP-2 and MMP-9, probably because modification of these enzymes is restricted to the site of joint inflammation and serum detection can not truly mirror the local situation. Additional soluble factors correlating with joint damage should be investigated as possible markers for monitoring anti-TNFalpha therapy.

Adult↗
PubMedDate not supplied

Percoll density gradient centrifugation. (An improved method for the enrichment of lymphocyte subsets mediating different activities).

Lymphocyte fractions obtained by Percoll density gradient centrifugation were assayed for their cytotoxic activities both in NK and ADCC cytotoxic systems. Furthermore, the release of a mediator, platelet slowing factor from the same subsets, was evaluated. Different mitogens (phytohemagglutinin, concanavalin A and lipid A) have been used for this purpose. The maximum of cytotoxic activities was recovered in E+ cell-enriched fractions. On the other hand, lipid A was able to stimulate the PSF production from enriched B cells (fraction I); phytohemagglutinin induced the release of PSF from E+ fractions (II and III) and concanavalin A from fraction II only. Our results suggest that Percoll density gradient is a very reproducible method in obtaining lymphocyte subsets enriched in cells mediating either cytotoxic activities or lymphokine release.

Antibody-Dependent Cell Cytotoxicity↗
PubMedDate not supplied

Natural and antibody-dependent cellular cytotoxicity in patients with active sarcoidosis.

Lymphocyte surface markers, natural killer activity, antibody-dependent cellular cytotoxicity and lymphocyte binding to target cells were evaluated in a group of 16 subjects with active sarcoidosis. A reduction of E-RFC and a relative increase of EA-RFC were observed. At the same time, ADCC activity was similar to that of normal controls, while NK cytotoxicity was significantly decreased. On the other hand, the percentage of conjugates between lymphocytes and target cells was lower than in controls. These observations account for a selective defect of NK activity, suggesting that the NK assay might be an useful tool to support the impairment of cellular immunity in active sarcoidosis.

Adult↗
PubMedDate not supplied

Oxidative burst and lysosomal enzyme release by polymorphonuclear cells in type IIa, type IIb and type IV primary hyperlipoproteinaemia.

Several findings pint out the occurrence of a strict relationship between lipoproteins and immunoresponsiveness. In this regard, in vitro lipoproteins pretreatment of mononuclear cell suspensions leads to an inhibition of Natural Killer (NK) cytotoxicity or T- and B-mediated immune functions. These results have an in vivo counterpart, since an impairment of either T-driven B cell polyclonal differentiation or phagocyte chemotaxis, phagocytosis and killing has been shown in patients with type IIa and type IIb primary hyperlipoproteinaemia. On the contrary, these activities fall within normal range in type IV hyperlipoproteinaemic subjects. To further address the potential role of polymorphonuclear cells (PMN) in atherosclerotic process, in the present report PMN-mediated superoxide anion (O2-) generation, hydrogen peroxide (H2O2) production, beta-glucuronidase and myeloperoxidase release have been assessed in similar groups of patients. Results provide a clearcut evidence for a significant enhancement of oxidative metabolism by either suspended or adherent to plastic PMN in type IIa primary hyperlipoproteinaemia only. These data were further confirmed by the observation that the same cell suspensions exhibit a significant increase of H2O2 generation and/or beta-glucuronidase and myeloperoxidase release. By contrast, PMN metabolic pathway in type IIb and type IV patients mimics that observed in healthy individuals. In the light of the well known increase of serum low-density lipoproteins (LDL) in type IIa primary hyperlipoproteinaemia, these findings suggest that also PMN may play an important role in the development of atherosclerosis. The augmented oxidative responsiveness may, in fact, give rise to LDL oxidation, which is in turn responsible for foam cell generation through an exaggerated uptake of oxidized LDL by macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗