The fibrinolytic system components are increased in systemic sclerosis and modulated by Alprostadil (alpha1 ciclodestryn).

Objectives: To evaluate urokinase plasminogen activator (u-PA), urokinase plasminogen activator soluble receptor (su-PAR), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) plasma levels in SSc patients (pts) versus healthy controls and their modulation by intravenous alphacyclodestrine (Alprostadil).

Methods: Plasma levels of u-PA, su-PAR, PAI-1 and t-PA were measured in 40 SSc (34 lSSc and 6 dSSc) pts and in 30 healthy controls. In SSc, blood was drawn before and after 3 consecutive daily of Alprostadil infusion (60 mg in 250 cc NaCl 0.

Deflazacort modulates the fibrinolytic pattern and reduces uPA-dependent chemioinvasion and proliferation in rheumatoid arthritis synoviocytes.

Objective: Extracellular fibrinolysis, controlled by the cell-associated fibrinolytic system (urokinase plasminogen activator, uPA; uPA receptor, uPAR; plasminogen activator inhibitor type-1, PAI-1), is involved in cartilage damage generation and in rheumatoid arthritis (RA) synovitis. Since steroids reduce the rate of radiological progression of RA, we planned to evaluate in healthy and RA synoviocytes the effects of the steroid deflazacort on uPA, uPAR and PAI-1 expression, and subsequent phenotypic modifications in terms of uPA/uPAR-dependent invasion and proliferation.

Methods: uPA, uPAR and PAI-1 levels were studied by ELISA, RT-PCR (uPAR) and zymography (uPA) in synoviocytes from four RA patients and four healthy controls.

Rheumatoid synovial fibroblasts constitutively express the fibrinolytic pattern of invasive tumor-like cells.

Objective: In rheumatoid arthritis (RA) the synovial membrane proliferates and invades the underlying tissues. The cell-associated fibrinolytic system (urokinase-type plasminogen activator, uPA; uPA receptor, uPAR; plasminogen activator inhibitor-type 1, PAI-1) is pivotal in cell invasion and proliferation. For this reason, the expression and the role of such enzymatic system was investigated in synovial fibroblasts (SF) of normal and RA patients.

Expression of interleukin-21 receptor in epidermis from patients with systemic sclerosis.

Objective: To examine the expression and regulation of interleukin-21 (IL-21) and IL-21 receptor (IL-21R) in patients with systemic sclerosis (SSc; scleroderma).

Methods: Skin biopsy specimens were obtained from 23 patients with SSc and 15 healthy controls. IL-21/IL-21R messenger RNA (mRNA) was quantified using real-time polymerase chain reaction (PCR).

Differential expression of tissue kallikrein in the skin of systemic sclerosis.

Systemic sclerosis (SSc) is characterised by ischemic damage, impaired angiogenesis and skin fibrosis. Tissue kallikrein (t-kallikrein) is involved through kinins in inflammation, vasorelaxation and angiogenesis. T-kallikrein is synthetised by endothelial, smooth muscle, and inflammatory cells and, in skin, also by dark cells of the sweat glands, where it is involved in sweat formation.

Increased circulating levels of tissue kallikrein in systemic sclerosis correlate with microvascular involvement.

Background: In systemic sclerosis (SSc) the lack of an angiogenic response to hypoxia may be due to inappropriate synthesis of angiogenic and angiostatic factors. Tissue kallikrein (t-kallikrein), regulating the kallikrein-kinin system and acting on the microcirculation, is a potent angiogenic agent, and kallistatin is its natural inhibitor.

Objective: To evaluate, in patients with SSc, t-kallikrein and kallistatin levels and their correlation with clinical features and measures of microvascular involvement.

[Peripheral nervous system in limited systemic sclerosis].

Objectives: PNS is involved in Systemic Sclerosis (SSc) since the earliest phases. Our aim is to perform an ultrastructural study on skin PNS fibers in SSc.

Methods: Skin biopsies were taken from forearms of 8 patients affected by limited SSc (lSSc) and 3 controls and processed for transmission electron microscopy (TEM).

[The treatment of skin ulcers in patients with systemic sclerosis].

Systemic Sclerosis (Ssc) is a complex disease of the connective tissue, characterized by progressive thickening and fibrosis of the skin and the internal organs and by diffused damage of the microvascular system. The fibrosis ones of the skin associated to the characteristic vascular alterations lead to the genesis of ulcers, more or less extended, often multiple, peripheral localization, chronic course, painful, able to influence patient's quality of life. Indeed, immunity reactivity, the thinning and the loss of elasticity of the skin, the peripheral neurological damage and the eventual drug assumption that can reduce regenerative/reparative abilities, can easily make an ulcer chronic and become infected complicating still more the patient disease, rendering more difficult the cure often, ulcer evolves to gangrene, and in some cases, in amputation too.

Mortality in systemic sclerosis: an international meta-analysis of individual patient data.

Purpose: Studies on mortality associated with systemic sclerosis have been limited by small sample sizes. We aimed to obtain large-scale evidence on survival outcomes and predictors for this disease.

Methods: We performed a meta-analysis of individual patient data from cohorts recruited from seven medical centers in the United States, Europe, and Japan, using standardized definitions for disease subtype and organ system involvement.

Estrogens and neuropeptides in Raynaud's phenomenon.

Raynaud's phenomenon (RP) is characterized by ischemia and reperfusion of the extremities. Vasomotor instability is due to a microcirculatory disturbance that may be linked to different events involving the endothelium or peripheral nerve terminals. Endothelium and nerve endings "sense" the modifications of the microenvironment and both of them release factors that contribute to find a balance between vasolidation and vasoconstriction.

Neurogenic aspects of inflammation.

The relationship between the inflammatory process and the nervous system is twofold. The nervous system is activated by inflammation which causes inflammatory pain and impaired motor function. Conversely, the nervous system acts back on the peripheral process.

Circulating leptin levels in juvenile idiopathic arthritis: a marker of nutritional status?

Background: Weight loss is common in juvenile idiopathic arthritis (JIA) and has been positively correlated with an increase in the production of proinflammatory cytokines.

Objective: To assess if plasma leptin is a mediator of cytokine dependent decreased food intake during inflammatory diseases and if it is increased in JIA.

Methods: Leptin levels were determined in 31 patients with polyarticular disease and in 37 with oligoarticular disease; 32 healthy children served as controls.

Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist.

Objective: Recurrent digital ulcers are a manifestation of vascular disease in patients with systemic sclerosis (SSc; scleroderma) and lead to pain, impaired function, and tissue loss. We investigated whether treatment with the endothelin receptor antagonist, bosentan, decreased the development of new digital ulcers in patients with SSc.

Methods: This was a randomized, prospective, placebo-controlled, double-blind study of 122 patients at 17 centers in Europe and North America, evaluating the effect of treatment on prevention of digital ulcers.

Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune diseases, with special reference to systemic sclerosis and multiple sclerosis.

Autologous haematopoietic stem cell transplantation is now a feasible and effective treatment for selected patients with severe autoimmune diseases. Worldwide, over 650 patients have been transplanted in the context of phase I and II clinical trials. The results are encouraging enough to begin randomised phase III trials.

Topical application of nerve growth factor in human diabetic foot ulcers. A study of three cases.

Three diabetic patients with leg or foot ulcers unresponsive to conventional therapies were treated with topical application of Nerve Growth Factor (NGF). The results showed that NGF promotes healing after 5-14 weeks of treatment. This study suggests that the use of topical application of NGF may represent a new useful tool for the management of difficult diabetic ulcers.

Matrix metalloproteinase 12-dependent cleavage of urokinase receptor in systemic sclerosis microvascular endothelial cells results in impaired angiogenesis.

Objective: Defective angiogenesis, resulting in tissue ischemia, is particularly prominent in the diffuse form of systemic sclerosis (SSc). The present study was undertaken to identify possible differences between normal and SSc microvascular endothelial cells (MVECs) in the expression of the cell-associated urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) system, which is critical in the angiogenic process.

Methods: MVECs were isolated from the dermis of healthy individuals and from the dermis of patients with diffuse SSc.

Gamma/delta T cells in placenta and skin: their different functions may support the paradigm of microchimerism in systemic sclerosis.

Increased amounts of foetal cells persisting after pregnancy could be involved in the pathogenesis of systemic sclerosis (SSc) and other autoimmune diseases. Evidence suggests a specific role for a subset of T lymphocytes showing the gamma/delta T cell receptor (TCR) at the foetal/maternal interface. gamma/delta T cells significantly increase in the early pregnancy decidua and recognize trophoblast antigens, probably a highly evolutionarily conserved molecule such as Hsp60 or Hsp60-derived peptides, and are likely to suppress the maternal anti-foetal immune response via TGFbeta production, thus contributing to pregnancy maintenance.

Regulation of substance P mRNA expression in human dermal microvascular endothelial cells.

Vascular endothelial cells have been identified as a source of substance P (SP) which may act in an autocrine/paracrine fashion to bring about nitric oxide (NO)-dependent vasodilatation and mitogen-induced cell division or immunologic and inflammatory responses. Whilst SP is localised in and released from endothelial cells, an endothelial mRNA expression of SP has not previously been shown. In the present study, mRNA expression of SP in human dermal microvascular endothelial cells is demonstrated using in situ hybridisation techniques with enhancement procedures.

The expression of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis.

Objective: To describe cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) expression in muscle tissue in patients with idiopathic inflammatory myopathies (IIM) - dermatomyositis (DM) and polymyositis (PM) and to find out if any differences between affected and non-affected muscles detected by MRI exist.

Methods: Samples of muscle tissue from 7 patients with dermatomyositis (DM) and from 4 with polymyositis (PM) were obtained by needle biopsy from affected and non-affected sites distinguished by magnetic resonance imaging. In situ hybridization with antisense mRNA probes was employed to detect COX-1, COX-2 and 5-LOX mRNA.

Infliximab in spondyloarthropathy associated with Crohn's disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations.

Objective: To evaluate the efficacy and tolerability of anti-tumour necrosis factor alpha (TNFalpha) monoclonal antibody (infliximab) in the treatment of spondyloarthropathy (SpA) associated with active and inactive Crohn's disease (CD).

Methods: Twenty four patients with SpA associated with active or inactive CD (16 active, 8 quiescent) were treated with anti-TNFalpha monoclonal antibody (infliximab) with repeated infusions for a period of 12-18 months. The treatment aimed at ameliorating the general musculoskeletal and spinal pain, controlling peripheral arthritis and enthesitis, decreasing the BASDAI score, modifying acute phase reactants, and reducing CD activity.