Evaluation of foot static disturbances in patients with rheumatic diseases.

OBJECTIVES: Rheumatic diseases such as osteoarthritis and rheumatoid arthritis constitute the most frequent pathological states leading to the development of foot deformities, which reduce quality of life and cause disability. The aim of the present study was to compare the results of plantoconturographic examinations, obtained by means of a computer podoscope, in osteoarthritis and rheumatoid arthritis patients. Special attention was paid to the differences in the values of each parameter determining the level of foot function. MATERIAL AND METHODS: The study was performed in 94 female patients divided into two groups according to the type of disease. There were 54 patients with rheumatoid arthritis and 40 with osteoarthritis. The control group consisted of 34 healthy women. The plantographic assessment of static foot structure was carried out by means of a device for computer-aided foot examination. RESULTS: A fallen transverse arch of the right foot was statistically much more frequent in the rheumatoid arthritis patients than in osteoarthritis patients or the control group (p < 0.005 and p < 0.05, respectively). Significant differences in the values of the Wejsflog index were observed in the case of left foot between rheumatoid arthritis patients and the control group (p < 0.05). Similarly, there were statistically significant differences in the values of the hallux valgus angle (α) for the right foot between rheumatoid arthritis and osteoarthritis patients or control group (in both cases p < 0.05). CONCLUSIONS: Rheumatic diseases predispose patients to disturbances of static foot function. The obtained results highlight the importance of diagnosing foot static disturbances in the prevention of destructive changes affecting the functioning of osteoarthritis and rheumatoid arthritis patients.

Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 following rituximab therapy in patients with rheumatoid arthritis refractory to anti-tumor necrosis factor blockers.

In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20-30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression.

Serum chemokines in patients with rheumatoid arthritis treated with etanercept.

Chemokines promote leucocyte traffic into the synovium, leading to the initiation and progression of the rheumatoid arthritis (RA). The aim of the study was to determine the effects of etanercept, a soluble tumour necrosis factor receptor (sTNFr), on the serum chemokines levels in patients with active RA. Patients were treated with 50 mg of subcutaneous injection of etanercept per week and methotrexate (10-25 mg/week). Serum levels of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA at months 0, 3, 6, 9 and 12, prior to injection. 3-month treatment with etanercept diminished serum concentrations of IL-8, RANTES and MCP-1 (P < 0.05, P < 0.01 and P < 0.001, respectively). Subsequent etanercept administrations prolonged decrease in serum chemokines levels and in the case of IL-8 even intensified the reduction of its concentration in serum. These changes were accompanied by significant decrease of disease activity score (DAS28) (in all cases P < 0.001). Prior to the first etanercept administration, serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) and DAS28. Following next drug injection such associations were less or not significant. Therapy with etanercept and MTX not only caused a clinical improvement but also diminished serum chemokines levels in RA patients. Further treatment with etanercept sustained chemokines suppression.

Vascular endothelial growth factor in systemic lupus erythematosus: relationship to disease activity, systemic organ manifestation, and nailfold capillaroscopic abnormalities.

INTRODUCTION: The aim of the study was to evaluate whether vascular endothelial growth factor (VEGF) serum level is associated with systemic organ involvement, microvascular changes as determined by nailfold capillaroscopy, and disease activity of systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Serum levels of VEGF were determined by an enzyme-linked immunosorbent assay in 47 SLE patients and in 30 healthy controls. Nailfold capillaroscopy was performed in all patients and healthy subjects. RESULTS: Morphological changes were observed by nailfold capillaroscopy in 45 of 47 (95.7%) SLE patients. Mild capillary changes were found in 16 (34%), moderate in 21 (44.7%), and severe in 8 (17%) SLE patients. All patients with systemic organ involvement showed severe or moderate changes in nailfold capillaroscopy. In comparison with the control group, a higher serum concentration of VEGF in SLE patients was demonstrated (p<0.05). Furthermore, significant differences in VEGF serum concentration between SLE patients with systemic involvement and controls were found (p<0.01). Comparison between patients with active and inactive SLE according to SLEDAI score showed a significantly higher concentration of VEGF in the sera of patients with active SLE (p<0.01). The SLE patients with severe and moderate changes in nailfold capillaroscopy showed significantly higher VEGF serum levels than SLE patients with mild changes (p<0.05) or healthy controls (p<0.01). Moreover, the VEGF serum level correlated significantly with ESR (r=0.580, p<0.0001) and CRP (r=0.512, p<0.005). CONCLUSIONS: Our data suggest that VEGF serum level may be a useful marker of disease activity and internal organ involvement in SLE patients. Abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with systemic manifestation in SLE.

The changes in monosaccharide composition of immunoglobulin G in the course of rheumatoid arthritis.

The objective of this study was to determine whether galactosylation of immunoglobulin G (IgG) in patients with rheumatoid arthritis (RA) correlates with severity and duration of illness. Serum IgG glycosylation from 50 patients with RA in comparison with 30 healthy controls was analyzed. IgG from sera was isolated and monosaccharide composition was determined by means of gas chromatography. Ratio of galactose to mannose content was calculated. Patients were divided into groups according to three different criteria: disease duration, severity of RA (disease activity score index), and radiological degree of advancement of illness according to Steinbrocker. In patients with RA, significant decrease (p<0,01) of galactose ratio was observed in comparison with healthy control. In patients with long duration of RA (more than 15 years), significant decrease of galactose (p<0.05) ratio in comparison with patients who have had arthritis for less then 5 years was observed. For the group of patients with severe RA, we found reduction of galactose (p<0.001) ratio vs the group of patients in remission. For those patients who had radiological stage IV according to Steinbrocker, IgG galactose (p<0.01) content per oligosaccharide chain were also more decreased than in those patients who had stage I RA. Decreased galactosylation and of IgG in RA was observed. The lack of this carbohydrate component of IgG correlates with severity and duration of RA and could be used in monitoring the progression in early arthritis.

A study on vascular endothelial growth factor and endothelin-1 in patients with extra-articular involvement of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with a wide range of extra-articular manifestations. Recent studies emphasise a key inflammatory role of the endothelial cells, either by overexpression of inflammatory mediators or by the proliferation of new blood vessels, in the disease process leading to the systemic organ involvement. To evaluate the relationship between internal organ manifestations and immunological markers of endothelial activation, serum levels of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were determined by an enzyme-linked immunosorbent assay in 64 RA patients and in 32 healthy controls. In comparison with a control group, higher serum concentrations of VEGF and ET-1 (p<0.001) in RA patients were demonstrated. A comparison between both RA groups with (20 patients) and without systemic involvement (44 patients) showed significantly higher concentrations of VEGF (p<0.05) and ET-1 (p<0.01) in the sera of patients with systemic manifestation. Moreover, a significant positive correlation between VEGF and ET-1 (r=0.475, p<0.001) in RA patients was found. A positive correlation between VEGF and Disease Activity Score (DAS) 28 index (r=0.39, p<0.005) as well as erythrocyte sedimentation rate (ESR) (r=0.564, p<0.0001) and C-reactive protein was found. ET-1 serum level correlated significantly with ESR (r=0.326, p<0.05) and DAS 28 index (r=0.307, p<0.05). These results suggest that the elevated serum levels of VEGF and ET-1 are associated with systemic organ involvement in RA patients and may play a key role in the pathogenesis of extra-articular manifestation of the disease.

[Matrix metalloproteinases and tissue inhibitors of metalloproteinases in the pathogenesis of rheumatoid arthritis]. / Rola metaloproteinaz i tkankowych inhibitorów metaloproteinaz w patogenezie reumatoidalnego zapalenia stawów.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints characterized by the accumulation of mononuclear cells and the proliferation of the synovium-lining layer. The role of lymphocytes, macrophages and fibroblasts infiltrating the synovium is not fully understood. These cells are supposed to be involved in the tissue destruction by several mechanisms, including the production of proinflammatory cytokines and matrix metalloproteinases. Matrix metalloproteinases (MMPs) are the enzymes that participate in the proteolytic degradation and remodelling of the extracellular matrix. Their action is controlled by tissue inhibitors of metalloproteinases (TIMPs). In this review we describe the role of metalloproteinases and their tissue inhibitors in the pathogenesis of rheumatoid arthritis.

Changes of glycosylation of IgG in rheumatoid arthritis patients treated with methotrexate.

PURPOSE: In patients with active rheumatoid arthritis (RA) decrease of galactosylation is correlated with disease activity. The aim of our study was to evaluate an effect of methotrexate therapy on glycosylation disturbances of IgG in RA patients. MATERIALS/METHODS: IgG glycosylation in 40 patients with active RA treated with methotrexate for 12 months prior to and after treatment were compared. The control group consisted of 20 healthy volunteers. IgG glycosylation was assessed using biotinylated lectins and immunosorbent ELISA assay. For galactose specificity Datura stramonium lectin (DSA), for sialic acid Sambucus nigra (SNA) and Maackia amurensis (MAA) and for fucose residue Areulia auranta (AAA) lectins were used. RESULTS: In RA-cases N-glycan galactosylation and sialylation of IgG before treatment were significantly lower than in healthy subjects (for DSA, MAA lectins p<0.001 and SNA p<0.05). Significant increase of IgG galactosylation and sialylation in RA patients after therapy (for DSA, MAA and SNA lectin p<0.05) was detected. Moreover the glycosylation disturbances of N-glycan IgG were strongly associated with changes of disease activity based on disease activity score. For fucose residues significantly higher absorbency of AAA lectin in RA patients before treatment was observed compared to control subjects (p<0.05) and slightly, not significantly decreased after MTX therapy. CONCLUSIONS: Defect of galactosylation of IgG in RA patients is a useful marker of disease activity that may be used for the assessment of therapy effectiveness. The role of IgG fucosylation and sialylation in RA pathogenesis has still to be determined.

Soluble adhesion molecules (sVCAM-1, sE-selectin), vascular endothelial growth factor (VEGF) and endothelin-1 in patients with systemic sclerosis: relationship to organ systemic involvement.

Systemic sclerosis (SSc) is a chronic, multisystemic, autoimmune disease characterised by vascular changes and varying degrees of fibrosis of the skin and visceral organs. Organ systemic involvement in SSc is associated with an altered function of endothelial cells, perivascular infiltrating mononuclear cells and interstitial fibrosis. To evaluate the relationship between systemic manifestations and immunological markers of endothelial cell activation, serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were determined by an enzyme-linked immunosorbent assay in 31 SSc patients and in 30 healthy controls. In comparison with the control group, higher serum concentrations of sVCAM-1, sE-selectin, VEGF and ET-1 were detected in SSc patients (in all cases p<0.001). Elevated concentrations of sVCAM-1 (p<0.05), sE-selectin (p<0.05), VEGF (p<0.05) and ET-1 (p<0.01) dominated in the serum of SSc patients with organ systemic involvement compared to those without systemic manifestation of the disease. These results suggest that the serum levels of sVCAM-1, sE-selectin, VEGF and ET-1 may reflect the extent of internal organ involvement in SSc patients and point to a pathogenic role of these molecules in systemic manifestation of the disease.

[Defect of glycosylation of immunoglobulin G in rheumatoid arthritis patients]. / Zaburzenia glikozylacji immunoglobuliny G w przebiegu reumatoidalnego zapalenia stawów.

Rheumatoid arthritis (RA) is a multisystem disorder in which immunological abnormalities result in symmetrical joint inflammation, articular erosion, and extra-articular involvement. The etiology of RA is still unknown, but a defect in the glycosylation of IgG may be involved in its immunopathogenesis. Several studies have shown a correlation between the amount of IgG lacking galactose and the activity of RA. IgG galactosylation has been shown to be a useful marker of early RA and an indicator of poor prognosis. Analysis of IgG galactosylation may offer an insight into disease pathogenesis and may also be useful in RA diagnosis.

[Immunopathological disturbances in systemic sclerosis]. / Aspekty immuno-patologiczne twardziny ukladowej.

Systemic sclerosis (SSc) is a disorder of the connective tissue characterized by the vascular dysfunction and progressive fibrosis of the skin, and various internal organs, which results in their dysfunction and failure. Activation of the immune system seems to play an important role in the pathogenesis of the disease. Contribution of the immune mechanisms to the development of the disease is indicated by the presence of the typical auto-antibodies, inflammatory cells infiltration in the skin and internal organs, and activation of cells participating in the immune response. Activation of the immune cells leads to release of proinflammatory/profibrotic cytokines and growth factors which in turn stimulate extensive proliferation of fibroblasts and collagen production. Activation of the immune system may also lead to impairment of endothelial function and development of angiopathy typical for systemic sclerosis, and subsequently chronic ischaemia of the affected tissues. In this review we describe the abnormalities of endothelial cells, T and B cells, and fibroblasts in patients with systemic sclerosis.

[Correlations between serum matrix metalloproteinase (MMP-1, MMP-3, MMP-9, MMP-13) concentrations and markers of disease activity in early rheumatoid arthritis]. / Korelacje pomiedzy stezeniem metaloproteinaz (MMP-1, MMP-3, MMP-9 i MMP-13) w surowicy krwi a wskaznikami aktywnosci choroby we wczesnym okresie reumatoidalnego zapalenia stawów.

The purpose of this study was to analyse the correlations between serum concentrations of the matrix metalloproteinases (MMP-1, MMP-3, MMP-9, MMP-13) and clinical markers of disease activity in patients with early rheumatoid arthritis (RA). The study group consisted of 30 RA patients, untreated with disease modifying antirheumatic drugs (DMARDs) or corticosteroids, with disease duration less than 3 years. The analysis of serum concentrations of MMPs was based on a quantitative sandwich ELISA. We observed the positive significant correlations between studied MMPs and clinical markers of disease activity, such as number of swollen joints or erythrocyte sedimentation rate (ESR). Furthermore, we revealed significant correlations between serum MMP-1, MMP-3, MMP-9, MMP-13 concentrations and disease activity score (DAS) (p < 0.01; p < 0.001; p < 0.001; p < 0.05 respectively). We conclude that studied matrix metallo-proteinases might be useful clinical markers of disease activity in early rheumatoid arthritis.

The influence of Multiwave Locked System (MLS) laser therapy on clinical features, microcirculatory abnormalities and selected modulators of angiogenesis in patients with Raynaud's phenomenon.

The aim of this study was to investigate the influence of the Multiwave Locked System (MLS) laser therapy on clinical features, microvascular changes in nailfold videocapillaroscopy (NVC) and circulating modulators releasing as a consequence of vascular endothelium injury such as vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2) in patients with primary and secondary Raynaud's phenomenon. Seventy-eight RP patients and 30 healthy volunteers were recruited into the study. All patients with RP received MLS laser irradiation for 3 weeks. Clinical, NVC and laboratory investigations were performed before and after the MLS laser therapy. The serum concentration of VEGF and Ang-2 were determined by an enzyme-linked immunosorbent assay (ELISA). After 3 weeks of MLS laser therapy, the clinical improvement manifested by decreasing of the number of RP attacks, mean duration of Raynaud's attack and pain intensity in RP patients was observed. After MLS laser therapy in 65% of patients with primary and in 35% with secondary RP, an increase in the loop number and/or a reduction in avascular areas in NVC were observed. In comparison with a control group, higher serum concentration of VEGF and Ang-2 in RP patients was demonstrated. After MLS laser therapy, a reduction of Ang-2 in both groups of RP patients was found. Our results suggest that NVC may reflect microvascular changes associated with clinical improvement after MLS laser therapy in patients with primary and secondary RP. Ang-2 serum levels may be a useful marker of microvascular abnormalities in RP patients treated with MLS laser therapy.

[Therapeutic efficacy of peloid plasters in the treatment of osteoarthritis of the peripheral joints and spondylosis]. / Skutecznosc terapeutyczna plastrów borowinowych w leczeniu choroby zwyrodnieniowej stawów obwodowych i kregoslupa.

The objective of the study was to investigate the efficacy and tolerability of the peloid plasters in the group of 20 patients with osteoarthritis of peripheral joints (10 patients with gonarthrosis and 10 with omarthrosis) and 20 patients with spondylosis. This form of the pelotherapy decreased pain in joints after 10 days of the treatment. No allergic or other side effects were observed. Peloid plasters through the analgesic action improve the comfort of life and reduce the use of oral analgesic drugs.

[Kidneys in rheumatoid arthritis]. / Nerki w reumatoidalnym zapaleniu stawów.

Kidney pathology is a common phenomenon which is revealed in patients with rheumatoid arthritis (RA). Its incidence is estimated at 50-60% of all patients. It is an important clinical problem because it directly affects the outcomes of RA. Changes in the kidneys may result directly from either the underlying illness or complications due to various, including iatrogenic causes. In the following paper we present actual views on the subject of the known up-to-date causes of renal impairment in the course of RA.

[Serum tumor necrosis factor alpha (TNF-alpha) concentration correlates with soluble adhesion molecules and vascular endothelial growth factor (VEGF) in rheumatoid arthritis]. / Stezenie czynnika martwicy nowotworów alpha (TNF-alpha) koreluje ze stezeniem rozpuszczalnych form czasteczek adhezyjnych i naczyniowo-sródblonkowego czynnika wzrostu (VEGF) w reumatoidalnym zapaleniu stawów.

In present study we investigated whether the serum concentration of tumour necrosis factor alpha (TNF-alpha) is associated with soluble adhesion molecules and vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA) patients. Serum levels of TNF-alpha, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble E-selectin (sE-selectin) and VEGF were assessed by ELISA in 38 patients with RA. We demonstrated the TNF-alpha to correlate with sICAM-1 (p < 0.001), sVCAM-1 (p < 0.01) and VEGF (p < 0.01). No association was noticed between TNF-alpha and sE-selectin serum concentrations. Moreover, serum TNF-alpha, sICAM-1, sVCAM-1 and VEGF levels correlated with markers of RA activity such as the erythrocyte sedimentation rate, C reactive protein level and the number of swollen joints. Data presented in this report support the concept of the VEGF synthesis stimulation by TNF-alpha. Analysis of the serum TNF-alpha, sICAM-1, sVCAM-1 and VEGF levels may be useful in the prediction of the RA activity.

Intraoperative bleeding during endoscopic sinus surgery and microvascular density of the nasal mucosa.

PURPOSE: To evaluate the correlation between quality of the surgical field, intraoperative bleeding during endoscopic sinus surgery (ESS) and the density of microvasculature of the nasal mucosa. MATERIAL/METHODS: Nasal mucosa of 30 patients, operated for chronic rhinosinusitis, was biopsied to assess expression of CD34 antigen on vascular endothelium. Quality of surgical field was evaluated with Fromm-Boezaart scale at mean arterial pressure (MAP) of 70-80 mmHg. If at this MAP surgical field quality was not satisfactory further reduction of hemodynamic parameters was performed until 'bloodless surgical field' (grade 2 or lower) was achieved. The rate of intraoperative bleeding was calculated from the ratio of total blood loss and the operative time. The extent of the disease was assessed according to computed tomography findings using Lund-Mackay staging system. RESULTS: Significant positive correlation (Spearman correlation test; p<0.05) was found between CD34 antigen expression and quality of surgical field at MAP between 70 and 80 mmHg as well as the rate of intraoperative bleeding. More intense reduction of MAP was necessary to achieve 'bloodless surgical field' in patients with high CD34 expression than in those with moderate and low expression. Lund-Mackay score correlated with quality of surgical field but not with the rate of intraoperative bleeding. CONCLUSION: During ESS, it is microvascular density of the nasal mucosa rather than the extent of the disease that contributes to the intensity of intraoperative bleeding, although both factors negatively influence the quality of surgical field.

Association between type 1 diabetes and periodontal health.

PURPOSE: We assessed periodontal status in patients with type 1 diabetes and healthy individuals in relation to their glycemic control, smoking and inflammatory biomarkers. MATERIAL/METHODS: Periodontal status was examined in 107 patients with diabetes and 40 controls, using Oral Hygiene Index (OHI), Community Periodontal Index (CPI) and tooth number. CPI values of 0-2 and 3-4 were classified as non-periodontitis and periodontitis, respectively. Blood samples were analyzed for glucose, HbA1c, CRP, fibrinogen, interleukin-1 and tumor necrosis factor-alpha (TNF-α). RESULTS: Periodontitis was found in 15.0% of the controls and 57.9% of diabetic patients, including 40.0% of these with good metabolic control (GMC) and 59.5% of those with poor metabolic control (PMC). Severe periodontitis was more frequent in the PMC than in the GMC group and in the controls (26.0% vs. 20.0% vs. 5.0%). The PMC patients had lower number of sextants with CPI 0 and higher number of sextants with CPI 3 and CPI 4 as well as lower tooth number in comparison with the controls. The patients with periodontitis had higher TNF-α (p<0.001) and OHI (p<0.001) than the patients without periodontitis. The number of sextants with CPI 0 correlated negatively with fibrinogen and TNF-α levels, whereas the number of sextants with CPI 3 correlated positively with TNF-α and fasting glucose level. CONCLUSIONS: There is good evidence that type 1 diabetes increases the risk of periodontal disease. Our results suggest that poor metabolic control of diabetes together with smoking and inadequate oral hygiene increase the risk of severe periodontal destruction in patients with type 1 diabetes.

Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients.

The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p < 0.01) and sE-selectin (r = 0.274, p < 0.05) serum levels as well as between sTM and ET-1 (r = 0.273, p < 0.05) serum concentrations. We noticed also positive correlation between VEGF (r = 0.224, p < 0.05) and ET-1 (r = 0.471, p < 0.001) serum levels and disease activity, and also between VEGF serum concentration and grade of morphological changes observed by nailfold capillaroscopy (r = 0.458, p < 0.001). There was also positive correlation between capillaroscopic score and disease activity (r = 0.339, p < 0.01). Our data suggest that correlation between VEGF and both ET-1 and E-selectin serum levels as well as between sTM and ET-1 serum concentrations may reflect their participation in the pathogenesis of SLE. VEGF seems to reflect changes in microcirculation in the course of SLE, visualised by nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.

The changes in serum chemokines following leflunomide therapy in patients with rheumatoid arthritis.

We undertook this study to evaluate the effects of leflunomide, an oral pyrimidine synthesis inhibitor, on the serum chemokine levels in patients with active rheumatoid arthritis (RA) who were refractory to treatment with methotrexate (MTX) or did not tolerated MTX treatment. RA patients were supposed to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally for the 12 months). Serum concentrations of RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) were assessed by enzyme-linked immunosorbent assay before and after 3, 6, 9, and 12 months of treatment with leflunomide. Three months therapy with leflunomide caused reduction in serum RANTES and MCP-1 (in both cases, p < 0.001) levels. Decrease in the concentration of these chemokines persisted until the end of the study period but was less significant. In the case of IL-8, its serum levels significantly diminished after 6 months of therapy with leflunomide (p < 0.01) and remained stable to the end of the study. Changes in serum chemokine levels were accompanied by significant decrease of disease activity score (DAS; p < 0.001). Prior to the first dose of leflunomide, serum concentrations of studied chemokines correlated with marker of RA activity such as the erythrocyte sedimentation rate and IL-8 level with DAS. Furthermore, we demonstrated significant correlations between serum levels of RANTES, MCP-1, and IL-8. During study period, such associations were far less or not significant. Leflunomide, beside a clinical improvement, reduce serum chemokines concentrations in RA patients. Leflunomide seems to be an effective treatment for RA, alternative to current therapies.