RESUMEN
OBJECTIVES: Inflammation has been revealed to be associated with angiogenesis. Granulomatosis with polyangiitis (GPA) and immune complex small vessel vasculitis (ICSVV) are forms of systemic vasculitides of different pathogenesis. GPA is a necrotizing granulomatosis and ICSVV is associated with inflammation of postcapillary venules induced by deposits of immune complexes. The aim of the study was to determine serum levels of angiostatin and endostatin, natural angiogenesis inhibitors, in patients with GPA and ICSVV as well as healthy individuals. MATERIAL AND METHODS: Two groups of patients with GPA (20 patients) and ICSVV (20 patients) as well as 20 controls were investigated. All patients were investigated before initiation of immunosuppressive therapy or administration of corticosteroids. Angiostatin and endostatin levels were assayed with the ELISA method. RESULTS: Enhanced serum levels of angiostatin and endostatin were found in patients with GPA but not in those suffering from ICSVV. In patients with GPA increased levels of angiogenesis inhibitors correlated with the disease activity. A correlation between angiostatin and endostatin levels was observed in all groups of investigated individuals. CONCLUSIONS: It is suggested that formation of necrotizing granulation is associated with profound activation of angiogenesis and an increase in serum levels of inhibitors is a phenomenon occurring during blood vessel formation in the granulation tissue. The obtained results confirm involvement of angiogenesis in pathogenesis of at least some forms of vasculitides and suggest the need for continuation of investigations in this field.
RESUMEN
Tofacitinib is a newly approved small-molecule targeted synthetic disease-modifying antirheumatic drug. The drug was designed as a selective and specific inhibitor of pro-inflammatory receptor signalling. Tofacitinib inhibits the process of intracellular signalling from the receptor to the cellular nucleus and inhibits the inflammation process via a new pathway (inhibition of the Janus kinases), which is unavailable to biological medicines. Tofacitinib has been approved for use in the treatment of patients with moderate to severe active RA. The drug may be used in combination with methotrexate or another conventional synthetic disease-modifying antirheumatic drug or in monotherapy. The efficacy of tofacitinib has been confirmed in several clinical trials. The drug inhibits radiographic progression of the disease. The innovative mechanism of action of tofacitinib is a noteworthy feature because it offers hope of effective treatment for patients who fail to respond to other drugs. The presented article discusses the mechanism of action and the clinical application of tofacitinib. Tofacitinib represents a new group of disease-modifying antirheumatic drugs that can be placed on an equal footing with biological drugs already available.
RESUMEN
The aim of the study was to determine whether plasma levels of total glycosaminoglycans (GAGs), matrix metalloproteinases (MMPs) (MMP-3, MMP-10), and their tissue inhibitors (TIMPs) (TIMP-1, TIMP-2) as well as transforming growth factor ß (TGF-ß) differ in the patients with systemic sclerosis (SSc) in relation to the healthy subjects. Plasma samples were obtained from 106 people (64 patients with SSc and 42 healthy individuals) and measured for MMP-3, MMP-10, TIMP-1, TIMP-2, and TGF-ß levels using ELISA methods. GAGs isolated from plasma samples were quantified using a hexuronic acid assay. The plasma levels of total GAGs, TIMP-1, TIMP-2, and TGF-ß were significantly higher, while MMP-3 was significantly decreased in SSc patients compared to the controls. We have revealed a significant correlation between plasma GAGs and TGF-ß (r = -0.47) and TIMP-2 (r = 0.38), respectively. The results of this study revealed that remodeling of the extracellular matrix, reflected by quantitative changes in plasma glycosaminoglycans, occurs during systemic sclerosis. Thus, the alterations in GAG metabolism connected with SSc may lead to systemic changes in the properties of the connective tissue extracellular matrix.