Search

Objectives: The study aimed to investigate serum tenascin-C levels and its relationship with pathogenesis of Behçet's disease (BD) with inflammatory processes., Patients and Methods: This prospective and analytical study included 34 BD patients (19 males, 15 females; mean age: 31.5±8.2 years; range, 18 to 48 years) who met the 2014 International Criteria for Behçet's Disease and had no comorbidities and 37 healthy volunteers (21 females, 16 males; mean age: 29.6±5.3 years; range, 21 to 45 years). Sex, age, age at diagnosis, clinical and laboratory data, medication use, and smoking history of the participants were recorded. Serum tenascin-C levels were measured using a commercially available tenascin-C enzyme-linked immunosorbent assay kit., Results: There was no significant difference between the groups in terms of age (p=0.262) and sex (p=0.287). Serum tenascin-C levels were significantly lower in the BD group (10,824±7,612 pg/mL) compared to the control group (27,574±14,533 pg/mL, p<0.001). In the receiver operating characteristic analysis performed for the diagnostic value of tenascin-C level in BD, the sensitivity was determined as 79.4% and the specificity as 82.5% (p<0.001). No statistically significant difference was observed in tenascin-C levels in correlation with clinical characteristics, laboratory values, medication use, and smoking in the BD group., Conclusion: In contrast to other chronic inflammatory diseases, lower levels of tenascin-C were observed in patients with BD than in the healthy individuals, which can be attributed to the absence of prolonged chronic inflammatory course in BD. The fact that tenascin-C levels are high in other rheumatic inflammatory diseases but low in BD may be useful in the differential diagnosis of BD., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2024, Turkish League Against Rheumatism.)

Objectives: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc., Methods: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]., Results: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles., Conclusions: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

Introduction Zonulin is a protein that plays a role in the reversible regulation of epithelial permeability. As zonulin is released in large amounts into the intestinal lumen, it disrupts the integrity of the tight junctions and causes continuous migration of antigens to the submucosa. Consequently, it can trigger inflammatory processes and severe immune reactions. In severe cases, SARS-CoV-2 may have a major impact on the clinical manifestations of the disease by directly or indirectly affecting intestinal cells and triggering systemic inflammation. Therefore, our study aimed to investigate the role of one of the possible mediators, zonulin, in the severity of the COVID-19 infection. Methods  Thirty COVID-19 patients and 35 healthy controls were included in the study. Blood samples were taken from the patients on the 1st, 4th, and 8th days of hospitalization. Serum zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood count (white blood cell [WBC], neutrophil, lymphocyte, and platelet), biochemical parameters (serum lactic acid dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], D-dimer, ferritin, fibrinogen levels) were determined and chronic systemic disease states of the patients were assessed. Results  Serum zonulin levels were notably higher in the healthy control group compared to the patient group (p=0.003). Although there was an increase in the zonulin values by time in hospitalization, this rising was not significant. Conversely, ESR and CRP levels were significantly higher in the patient group (p<0.001). There was no significant difference between the two groups regarding gender, age, and WBC counts. Conclusion  The serum zonulin levels of COVID-19 patients with the mild clinical course were lower than the healthy control group. Moreover, serum zonulin levels were not correlated with ESR, CRP, and other inflammation markers. Our results suggest that low serum zonulin levels in COVID-19 patients might represent a mild disease course., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Okuyucu et al.)

Introduction Familial Mediterranean fever (FMF) is an inflammatory rheumatic disease that affects people in their reproductive period. The aim of this study was to investigate the number of gravida, ovarian reserve, and ovarian doppler characteristics in FMF patients. Methods The study design is cross-sectional. Between November 1, 2018, and October 31, 2019, 40 FMF patients, and 40 age-matched volunteers were included in the study. Early follicular phase follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), progesterone, and anti-Mullerian hormone (AMH) levels, as well as ovarian volume, antral follicle count (AFC), ovarian stromal artery doppler findings, and pelvic pathologies, were evaluated. Results The number of gravida, and the AFC was significantly higher in the control group (16.00 ± 5.22) compared to the patients with FMF (13.00 ± 4.09) (p = 0.026). LH values were significantly higher in the FMF group. Thirteen patients (32.5%) received anakinra and colchicine, and 27 patients (67.5%) received only colchicine. There was no significant difference between the patients receiving anakinra, and the patients receiving colchicine in terms of AMH, FSH, AFC, and E2 values. Conclusion FMF patients were found to have low gravida and AFC, and a significant portion was observed to have pelvic fluid and hydrosalpinx. In conclusion, the presence of pelvic fluid, hydrosalpinx, and low AFC persist in FMF patients despite colchicine and/or anti-interleukin-1 treatments. The low gravida may be related to these pathologies detected in patients with FMF., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Okuyucu et al.)

Background: Parenchymal neuro-Behçet's disease involvement is the most serious complication of Behçet's disease, and no sufficient data on its treatment exists. This study aims to investigate the efficacy and safety of infliximab treatment in neuro-Behçet's disease patients with parenchymal involvement., Materials and Methods: Patients who were diagnosed with Behçet's disease with parenchymal neurological involvement and underwent infliximab treatment for at least 12 months were included in the study. Demographic, clinical, and radiological data of the patients were accessed through the electronic database of our hospital., Results: This study comprises 19 patients who were diagnosed with neuro-Behçet's disease and used infliximab: 12 male and 7 female patients. The mean age of the patients was 36.5 ± 11.7 years, and the diagnostic age was 26.3 ± 10.8 years. The duration of treatment with infliximab was 32.3 months (minimum 11, max 79). In the 19 patients receiving infliximab treatment, 11 (58%) patients achieved remission (complete disappearance of neurological symptoms) and 7 (37%) patients achieved disease stability (no new neurological findings); steroid treatments were discontinued for these 18 patients. In addition, only 5 patients were concomitantly taking immunosuppressive drugs with the infliximab. Infliximab was discontinued after the development of a new parenchymal attack in the 9th month of infliximab treatment., Conclusion: In conclusion, parenchymal neurological involvement in Behçet's disease is an important cause of disability, and no sufficient data exists in literature on its treatment. The results of our study suggest that infliximab treatment was effective and safe in neuro-Behçet's disease parenchymal involvement for preventing long-term neurological attacks and discontinuing corticosteroid treatment., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Introduction: Coronavirus disease-2019 (COVID-19) with lung involvement frequently causes morbidity and mortality. Advanced age appears to be the most important risk factor. The receptor for advanced glycation end-product (RAGE) pathway is considered to play important roles in the physiological aging and pathogenesis of lung diseases. This study aimed to investigate the possible relationship between COVID-19 and RAGE pathway., Materials and Methods: This study included 23 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed tomography. Serum soluble-RAGE (sRAGE) levels were determined using enzyme-linked immunosorbent assay., Results: The sRAGE levels were significantly higher in the asymptomatic group than in the control group. Age, fibrinogen, C-reactive protein, and ferritin levels were higher and the sRAGE level was lower in the patients with lung involvement than in the asymptomatic patients., Conclusions: In this study, patients with high sRAGE levels were younger and had asymptomatic COVID-19. Patients with low sRAGE levels were elderly patients with lung involvement, which indicates that the RAGE pathway plays an important role in the aggravation of COVID-19.

Objective: This study aims to investigate the efficacy and reliability of infliximab treatment in Behcet's disease with vascular involvement., Methods: This single-center retrospective study included a total of 18 patients diagnosed with Behcet's disease with vascular involvement who were initiated infliximab treatment after exhibiting resistance to conventional immunosuppressive treatments., Results: Seventeen patients achieved remission with infliximab treatment. While 18 patients were receiving a median of 50 (IQR: 20-61) mg/day equivalent of methylprednisolone before infliximab treatment, after infliximab treatment, only four patients were receiving 4 mg/day equivalent of methylprednisolone ( p  < 0.001). Only 4 patients were receiving oral anticoagulant treatment during infliximab treatment, and compared to the patients who were not receiving oral anticoagulants, there was no significant difference between the two groups according to occurrence of new vascular events., Conclusion: Infliximab seems to be an effective and reliable treatment in Behcet's disease with vascular involvement and may also allow reduced dosage or even the discontinuation of corticosteroids. The results of our study suggest that oral anticoagulant use is unnecessary in Behcet's disease with vascular involvement. However, further long-term randomized controlled studies are needed to investigate the length of infliximab regimen, whether or not it should be discontinued, and if so, whether or not immunosuppressants should be given as maintenance after discontinuation.

Background: Idiopathic granulomatous mastitis is a rare inflammatory disease of the breast, for which there is a lack of consensus on the treatment protocol; it requires long-term follow-up and is associated with a high rate of relapse after surgical treatment. In this study, we report on the largest single-center cohort of idiopathic granulomatous mastitis treated with steroids + methotrexate., Methods: We retrospectively examined the data of 33 patients histopathologically diagnosed with idiopathic granulomatous mastitis who were evaluated by our Rheumatology or General Surgery Clinics between 2013 and 2016., Results: Of the 33 female patients (age: 38.64 ± 6.9 years), 24 were admitted with an initial diagnosis of idiopathic granulomatous mastitis, whereas 9 were admitted after surgical treatment. Remission was achieved in 87.9% of patients with steroid + methotrexate treatment, and there were no relapses during the 24-months follow-up period., Conclusions: Steroid + methotrexate treatment is an effective and reliable method for ensuring long-term remission in patients with idiopathic granulomatous mastitis diagnosis., (Copyright © 2020 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Epigallocatechin 3-gallate (EGCG) is a polyphenol that has been shown to have antioxidant and anti-inflammatory effects. In this study, collagen-induced arthritis (CIA) model, in Wistar albino rats, was used to elucidate the effect of EGCG on pathogenetic pathways in inflammatory arthritis. The levels of serum TNF-α, IL-17, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx); the expression levels of tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); histopathologically, perisynovial inflammation and cartilage-bone destruction were examined. In the sham group, serum TNF-α, IL-17, and MDA levels increased, while SOD, CAT, GPx levels, and the expressions of Nrf2 and HO-1 decreased. On the other hand, in the EGCG administered groups, serum TNF-α, IL-17, and MDA levels improved, while SOD, CAT, GPx levels and the expressions of Nrf2 and HO-1 increased. Moreover, histopathological analysis has shown that perisynovial inflammation and cartilage-bone destruction decreased in the EGCG administered groups. These results suggest that EGCG has an antiarthritic effect by regulating the oxidative-antioxidant balance and cytokine levels in the CIA model, which is a surrogate experimental model of rheumatoid arthritis., (© 2019 International Union of Biochemistry and Molecular Biology, Inc.)

Objective: Approximately 30-45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine-unresponsive or colchicine-intolerant FMF patients are limited; the most promising alternatives seem to be anti-interleukin-1 (anti-IL-1) agents. Here we report our experience with the off-label use of anti-IL-1 agents in a large group of FMF patients., Methods: In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti-IL-1 treatment for at least 6 months were reviewed., Results: In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18-68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1-48), and the mean colchicine dose was 1.7 mg/day (range 0.5-4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti-IL-1 treatment was used because of colchicine-resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6-98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine-resistant FMF patients were attack free. Serum levels of C-reactive protein, erythrocyte sedimentation rate, and 24-hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced., Conclusion: Anti-IL-1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine-resistant FMF patients., (© 2017, American College of Rheumatology.)

Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by widespread fibrosis of the skin and several visceral organs. The pro-fibrotic potential of interleukin (IL)-33 has been demonstrated by in both in vitro and in vivo settings; moreover, increased level of IL-33 has also been reported in patients with SSc. Therefore, the aim of the present study was to detect the potential association of IL-33 gene polymorphisms on the susceptibility of SSc. A total of 300 SSc patients and 280 healthy controls (HC) were enrolled in this multicentric preliminary candidate gene study. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms (SNPs) of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. There was no significant difference in terms of the allelic distributions and minor allele frequencies of evaluated four IL-33 polymorphisms between the SSc and HC groups (P > 0.05 for all). Moreover, the genotypic distributions of rs1157505, rs11792633 and rs1929992 polymorphisms were not significantly different (P > 0.05 for all). However, CC genotype of rs7044343 SNP was significantly higher in the SSc group compared to the HC group (P = 0.013, OR 1.75, 95 % CI 1.12-2.72). This preliminary candidate gene study demonstrates that rs7044343 polymorphism of IL-33 gene is associated with the susceptibility to the SSc in Turkish population. It may be suggested that IL-33 gene may be a candidate gene to research in SSc.

Background: The capillary networks are less dense and have irregular structures in scleroderma. These abnormalities result in lower capillary blood flow causing severe tissue hypoxia, which is a major stimulus for angiogenesis. However, current knowledge about compensatory angiogenesis is ambiguous in scleroderma. Bevacizumab is an inhibitor of vascular endothelial growth factor (VEGF)., Objectives: The aim of the present study is to evaluate the protective effects of bevacizumab in bleomycin (BLM)- -induced dermal fibrosis., Material and Methods: This study involved 4 groups of Balb/c mice (n = 10 per group). Mice in the control group received 100 μL/day of phosphate-buffered saline (PBS) subcutaneously, while the other 3 groups were given 100 μg/day of BLM (dissolved in 100 μL PBS) subcutaneously, for 4 weeks. Mice in BLM-treated 3rd and 4th groups also received bevacizumab (1 or 5 mg/kg twice a week, intraperitoneally). At the end of the fourth week, all mice were sacrificed and blood and tissue samples were obtained., Results: The BLM applications increased the dermal thicknesses, tissue hydroxyproline contents, and α-smooth muscle actin-positive (α-SMA+) cell counts, and led to histopathologically prominent dermal fibrosis. The bevacizumab treatments decreased the tissue hydroxyproline contents and dermal thicknesses, and these improvements were more prominent at doses by which α-SMA+ cell counts were markedly decreased, in the BLM-injected mice., Conclusions: In our study, inhibition of VEGF with bevacizumab treatments prevented the BLM-induced dermal fibrosis suggesting that VEGF expression contributes to the pathogenesis of scleroderma.

Systemic sclerosis (SSc) is a disease characterized by inflammation, vascular abnormalities and fibrosis. The role of Rho/Rho-kinase pathway was demonstrated in the pathogenesis of fibrosis, inflammation and vascular abnormalities. This study was aimed to investigate the relation between SSc and Rho/Rho-kinase gene polymorphisms. The study included 339 patients with SSc and 302 healthy subjects who were apparently healthy and at similar age and gender. Genotype distributions and allele frequencies were detected by using Chi-square test or Fisher's exact Chi-square test between groups, and the haplotype analysis was applied using online program (SHEsis). Significant association was found in a polymorphism in the ROCK1 gene (rs35996865), a polymorphism in ROCK2 gene (rs10178332), a polymorphism in RhoA gene (rs2177268) and two polymorphisms in RhoC gene (rs11102522 and rs11538960) with SSc disease (p < 0.0022). In this study, association between SSc disease and Rho/Rho-kinase gene polymorphisms was investigated for the first time; significant associations between ROCK1, ROCK2, RhoA and RhoC gene polymorphisms and SSc disease were demonstrated. The results strongly suggest that this SNP may be an important risk factor for development of SSc. However, further validation of these findings in an independent cohort is necessary.

Background/aim: Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc., Materials and Methods: A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system., Results: There were marked increases in the CC genotype (94.7% vs 81.8%, p<0.0001) and C allele frequencies (97.0% vs. 90.1%, p<0.0001) in the TRPM3 rs1328142, and TT genotype (19.0% vs. 7.8%, p=0.0002) in TRPM5 rs34551253 (Ala456Thr) polymorphism in SSc patients when compared to controls. TRPM3 gene rs1328142 polymorphism was also markedly associated with disease phenotype. However, no associations with the other 23 polymorphisms studied were found., Conclusion: This is the first study to examine the involvement of TRPM channel gene variations on the risk of SSc incidence. Our results suggest roles of TRPM3 and TRPM5 gene variants in the susceptibility to or clinical expression of SSc in the Turkish population., (Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Behçet's disease (BD) is a chronic inflammatory disease. Increased productions of cytokines including interleukin (IL)-1β and IL-18 are documented, and IL-1α and β gene polymorphisms are associated with susceptibility to the disease. IL-33 is a recently discovered member of IL-1 cytokine family. The aim of the study was to detect serum IL-33 level and IL-33 gene polymorphisms in a cohort of BD. Unrelated 117 patients with BD and 149 healthy controls (HC) were enrolled. Serum IL-33 levels were analyzed by enzyme-linked immunosorbent assay method. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. Serum IL-33 level was not significantly different in the BD and HC groups (p > 0.05). However, its level was lower in the active BD patients compared to the inactive ones and HC group (p = 0.044 and p = 0.037, respectively). There was no significant difference in terms of the genotypic and allelic distributions of rs1157505 and rs1929992 polymorphisms (p > 0.05 for all). However, the TT variants of rs7044343 and rs11792633 polymorphisms were very rare, and the T allele frequencies of these polymorphisms were lower, in the BD group compared to the HC group (p < 0.0001 for all). The rs7044343 and rs11792633 variants of IL-33 gene are associated with the decreased risk of BD in our cohort. Therefore, it may be concluded that IL-33 acts a protective role on the pathogenesis of BD.

Epidermal growth factor receptor (EGFR) and its ligands are commonly expressed by synovial cells. The aim of the present study was to detect the potential effect of lapatinib an inhibitor of EGFR tyrosine kinases on collagen-induced arthritis. Thirty Wistar albino female rats were randomized into three groups. Arthritis was induced by intradermal injection of chicken type II collagen with incomplete Freund's adjuvant. Serum TNF-α, IL-17, and malondialdehyde (MDA) levels were analyzed. Tissue superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities, and nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxgenase-1 (HO-1) expressions were determined. TNF-α, IL-17 and MDA levels, and Nrf2 and HO-1 expressions were lower in lapatinib-treated (30 mg/kg/day) group compared to sham group, while SOD, catalase, and GPx activities were higher (p < 0.05). Moreover, lapatinib ameliorated perisynovial inflammation and cartilage-bone destruction (p < 0.001). In conclusion, EGFR may have prominent pathogenic role and lapatinib may be an effective therapeutic option for arthritis.

Pemetrexed (PMTX) is an anti-folate drug as methotrexate. The purpose of this study was to assess the efficacy of PMTX on collagen-induced arthritis (CIA). Forty Wistar albino rats were randomized into four groups. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant. Animals were sacrificed at the 15th day after the onset of arthritis. Tumor necrosis factor alpha (TNF-α), interleukin (IL)-17, and malondialdehyde (MDA) levels were increased, and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were decreased in the arthritis group. In the PMTX-treated (0.2 and 1 mg/kg/week i.p.) groups, the levels of TNF-α, IL-17, and MDA were decreased; the activities of SOD, CAT, and GPx and the expressions of Nrf2 and HO-1 were restored, and perisynovial inflammation and cartilage-bone destruction were decreased. PMTX has anti-arthritic potential in the CIA model and may be a therapeutic agent for rheumatoid arthritis.

Integrin αvβ3 (vitronectin receptor) plays a prominent role in angiogenesis, a key pathogenic feature of rheumatoid arthritis (RA). Moreover, integrin αV (ITGAV) subunit gene has been associated with a susceptibility to RA. The aim of the present study was to detect the potential association between ITGAV gene polymorphisms and a susceptibility to RA in a Turkish cohort. DNA samples were harvested from 160 patients with RA and 144 healthy controls (HC). Three single-nucleotide polymorphisms of ITGAV gene (rs3738919, rs3768777, and rs10174098) were genotyped using real-time PCR. Serum vitronectin levels were analyzed in 30 RA patients, 28 Behçet's disease (BD) patients, and 30 HC subjects. There was no significant difference between the RA and HC groups in terms of the genotypic and allelic distributions of rs3738919 and rs10174098 polymorphisms. However, the prevalence of rs3768777-G allele was higher in the RA group than in the HC group (OR 2.3, 95 % CI 1.6-3.2, p < 0.0001). Moreover, there was a significant association between RA and the genotypic distribution of rs3768777 (GG + AG vs. AA: OR 2.1, 95 % CI 1.3-3.4; GG vs. AG + AA: OR 4.1, 95 % CI 2.1-7.8). Serum vitronectin levels were lower in the RA and BD groups than in the HC group (p ANOVA = 0.002). The rs3738919 and rs10174098 polymorphisms of the ITGAV gene seem not to be associated with susceptibility to RA in Turkish patients. However, rs3768777 increases the risk of RA in this group. These results suggest that the ITGAV gene may be a candidate gene for the etiopathogenesis of RA.

Systemic sclerosis (SSc) is an autoimmune disease of unknown etiology characterized by progressive fibrosis. Activated fibroblasts are mainly responsible for fibrosis in SSc. Galectin-3, a β-galactoside-binding lectin, plays many important regulatory roles in both physiological and pathological processes including proliferation, apoptosis, inflammation, and fibrosis. The purpose of this study was to assess the serum galectin-3 levels in patients with SSc. Thirty-seven SSc patients, 23 systemic lupus erythematosus (SLE) patients (serving as patient control group), and 28 healthy volunteers were enrolled in this study. Disease activity and severity scores were detected with Valentini disease activity index and Medsger disease severity scale in the SSc group and SLE disease activity index and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index in the SLE group. The serum levels of galectin-3, vascular endothelial growth factor, transforming growth factor-β, and interleukin-6 were determined. Compared to the control group, the galectin-3 levels were higher in the SSc and SLE groups. The galectin-3 levels were not correlated with the disease activity and severity indexes in both patient groups. But, the serum galectin-3 levels were higher in the active SSc and SLE subgroups than in the inactive SSc (4.6 ± 5.8 vs. 1.3 ± 1.1 ng/ml, p = 0.015) and SLE (17.4 ± 11.3 vs. 6.5 ± 8.9 ng/ml, p = 0.019) subgroups. These results suggest that galectin-3, which is associated with fibrosis and inflammation by previous studies, may be a prominent biomarker of disease activity in SSc.

Scleroderma is a chronic fibrotic disorder. Bortezomib, a proteasome inhibitor, is reported to attenuate experimentally induced renal and cardiac fibrosis. This study aimed to evaluate the preventive and therapeutic efficacies of bortezomib on a bleomycin (BLM)-induced scleroderma model. Dermal fibrosis was induced in Balb/c mice by subcutaneous BLM (100 μg/day) injections. Bortezomib (1.6 mg/kg twice/week) was applied intraperitoneally to BLM-injected mice during the first 3 weeks for preventive interventions and in the second 3 weeks for therapeutic interventions. IL-4 and TGF-β1 serum levels, dermal thicknesses, dermal inflammatory cell counts, and α-SMA-positive fibroblastic cell counts were determined, and type-I collagen, NF-κBp65, I-κBα, and JNK1 expressions were assessed. BLM applications increased serum IL-4 level, dermal inflammatory cell counts, α-SMA-positive cell counts, expression of type-I collagen, NF-κB, and JNK1, and dermal thickness in early stage of fibrosis, but serum IL-4 level and dermal inflammatory cell counts showed no increases in later stages. As a preventive intervention, bortezomib decreased dermal thickness, inflammatory cell infiltrations, fibroblastic activity, and expression of type-I collagen, NF-κB, and JNK1, but did not decrease fibroblastic activity and dermal thickness at later stages of fibrosis. Inflammatory status is prominent in the early stage of dermal fibrosis, but declines at later stages. In BLM-induced dermal fibrosis, bortezomib has a preventive anti-fibrotic and anti-inflammatory efficacy, but has no therapeutic anti-fibrotic efficacy in preexisting tissue fibrosis. These findings suggest that the effect of proteasome inhibition in early stages of dermal fibrosis may be related to its anti-inflammatory effects.

Objective: Systemic sclerosis (SSc) is an autoimmune chronic fibrotic disorder. Urotensin II (U-II) is predominantly a vasoactive peptide with fibrotic and prothrombotic features. Like endothelin-1 (ET-1), U-II could play an important role in SSc pathogenesis. We evaluated the possible role of the U-II gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to SSc in a Turkish population., Methods: A total of 189 patients with SSc and 205 healthy controls were enrolled in our study. We analyzed the genotype and allele frequencies of the U-II (UTS2) gene polymorphisms Thr21Met and Ser89Asn in patients with SSc and in controls., Results: We found that the Thr21Met polymorphism of the UTS2 gene was markedly associated with the risk of developing SSc (p < 0.0001), but there was no relationship between the Ser89Asn polymorphism and SSc (p > 0.05). Two haplotypes (MS and TS) were markedly associated with SSc (p < 0.05). There were significant associations between the genotype and allele frequencies of UTS2 gene Thr21Met polymorphism and cases with diffuse or limited SSc, systemic or lung involvement, finger flexion deformity, pitting scars at the fingertips, positive anticentromere, or positive antitopoisomerase 1 antibody groups., Conclusion: Our study shows the association between Thr21Met, but not Ser89Asn, in the UTS2 gene and SSc. The results strongly suggest that this single-nucleotide polymorphism may be an important risk factor in the development of SSc, and a powerful indicator of severe skin and lung involvement in patients with SSc.

Objectives: Ghrelin, an endogenous orexigenic peptide, has anti-inflammatory effects, down-regulates pro-inflammatory cytokines, and its altered levels are reported in various inflammatory diseases. The human preproghrelin (ghrelin/obestatin) gene shows several single nucleotide polymorphisms (SNPs) including Arg51Gln, Leu72Met, Gln90Leu, and A-501C. The aim of this study was to investigate the frequency, and clinical significance, of these four SNPs in a small cohort of Turkish patients with rheumatoid arthritis (RA)., Methods: The study included 103 patients with RA and 103 healthy controls. In the RA group, disease activity and disease-related damage were assessed using the Disease Activity Score-28 (DAS-28), and the modified Larsen scoring (MLS) methods. In all the participants, genomic DNA was isolated and genotyped by polymerase chain reaction and restriction fragment length polymorphism analysis., Results: The frequencies of ghrelin gene SNPs were 82.5 and 79.6% in the RA and control groups, respectively, and there were no significant differences in terms of genotype distributions and allele frequencies for these four SNPs between the groups. However, the A-501C SNP was found to be associated with early disease onset, and Gln90Leu SNP with less frequent rheumatoid factor positivity, in the RA group., Conclusion: A-501C SNP is associated with earlier onset of RA suggesting that genetic variations in the ghrelin gene may have an impact on RA., (Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Chronic inflammatory rheumatic diseases lead to increased prevalence of atherosclerosis. However, this early and accelerated atherosclerosis cannot be explained by traditional cardiovascular risk factors alone. The permanent overexpression of cellular adhesion molecules and pro-inflammatory cytokines in chronic inflammatory conditions may participate in accelerated atherosclerosis. Visfatin, a novel adipocytokine, has a potential insulin-like action and pro-inflammatory effects. Therefore, the aim of the study was to determine serum visfatin level and its association with common carotid intima-media thickness (IMT), which is a predictor of atherosclerosis, in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Behçet's disease (BD). The study involved 29 RA, 26 SLE, 25 SSc, 30 BD patients, and 29 healthy controls (HC). Serum levels of TNF-α, IL-6, and visfatin were analyzed using enzyme-linked immunosorbent assay method and homeostasis model assessment for insulin resistance (HOMA-IR) indexes, and IMTs were determined. Serum visfatin level was higher in the RA group than all the other groups. In addition, visfatin level was higher in the active BD subgroup than the inactive BD subgroup. In the study groups, visfatin levels were not correlated with HOMA-IR indexes and IMTs. Whereas visfatin serum concentration was not associated with insulin resistance and carotid atherosclerosis in selected rheumatic diseases, it was higher in the RA and active BD groups, but not in the SLE and SSc groups. Visfatin levels may be associated with Th1/Th2 balance. Further studies are needed for more precise elucidation of the pro-inflammatory activities of visfatin.

Rheumatoid arthritis (RA), a chronic inflammatory disease, leads to early and accelerated atherosclerosis; however, its pathogenesis is not yet fully documented. Salusin-α and β are novel bioactive peptides. Salusin-α suppresses macrophage foam cell formation, while salusin-β stimulates. Moreover, decreased serum salusin-α level has been reported previously in patients with coronary artery disease. The aims of the study were to assess serum salusin-α level and its association with predictors of atherosclerosis in a cohort of patients with RA. The study included 56 RA patients, 37 Behcet's disease (BD) patients, and 29 healthy controls (HC). TNF-α, IL-6 and salusin-α levels, homeostasis model assessment (HOMA-IR) index and common carotid intima-media thickness (IMT) were determined. In the RA and BD groups, salusin-α levels (p<0.001 and p<0.01, respectively) and IMTs (p<0.001 for both) were higher compared to the HC group. However, the level of salusin-α was not directly associated with the IMT in all the groups. Serum salusin-α levels are increased in RA and BD, although they have increased IMT. Salusin-α has been reported to have anti-atherogenic effects in previous studies. However, it seems that salusin-α does not directly affect the atherogenesis in RA and BD. Further studies are needed to understand the regulation of salusin-α and determination of its relations with the predictors of atherosclerosis in RA and BD., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background and Aims: The risks of insulin resistance and accelerated atherosclerosis are increased in chronic inflammatory diseases including rheumatoid arthritis (RA). Adipo-(cyto)kines are associated with insulin resistance, atherosclerosis and inflammation. This study aimed to determine serum adiponectin and vaspin levels and their associations with the predictors of atherosclerosis in RA and Behcet's disease (BD)., Methods: The study involved 56 patients with RA, 37 patients with BD, and 29 healthy controls (HC). Serum adiponectin and vaspin levels, homeostasis model assessment for insulin resistance (HOMA-IR) index, and common carotid intima-media thickness (IMT) were determined., Results: Serum adiponectin levels in both patient groups and serum vaspin level in only the RA group were higher, whereas serum vaspin level was lower in the active BD subgroup, compared to the HC group. However, adiponectin and vaspin levels were correlated with neither HOMA-IR index nor IMT in the RA group. Adiponectin level was correlated with DAS-28 and IL-6 level in the RA group, and it was higher in the active BD subgroup than in the inactive BD subgroup and the HC group., Conclusions: Adiponectin and vaspin levels are higher in RA but associated with neither HOMA-IR index nor IMT. Adiponectin is related with disease activity remarks in RA and BD. Therefore, it may be suggested that adiponectin may be involved in the regulation of inflammatory responses in inflammatory diseases. Moreover, in contrast to in RA, vaspin level declines in active BD, and these results suggest that different chronic inflammatory diseases exert different influences on either adipokines., (Copyright © 2010 IMSS. Published by Elsevier Inc. All rights reserved.)

Objectives: Pyrin/marenostrin, an inhibitory regulator of inflammation, is encoded by MEditerranean FeVer (MEFV) gene. Mutations of this gene are the cause of familial Mediterranean fever (FMF). A connection between MEFV gene mutations and rheumatic diseases has been suggested. The aim of this study was to explore the frequency and clinical significance of MEFV gene mutations in a cohort of Turkish patients with rheumatoid arthritis (RA)., Methods: The study included 103 patients with RA and 103 age-, sex- and origin-matched healthy controls (HC). In all participants, genomic DNA was isolated and genotyped using amplification refractory mutation system or restriction fragment length polymorphism for the eight MEFV gene mutations (E148Q, M694V, M694I, M680I, V726A, A744S, R761H, and P369S). In the RA group, disease activity was determined using the disease activity score-28 (DAS-28), and radiological damage was evaluated by the modified Larsen scoring method., Results: Carrier rates of MEFV gene mutations were 26/103 (25.2%) and 24/103 (23.3%) in the RA and HC groups, respectively (p>0.05, OR: 0.9, 95% CI: 0.48-1.71). In the RA group, while deformed joint count was significantly higher in the mutation carrier group than those of the non-carrier group (p<0.05), the level of C-reactive protein, DAS-28 and modified-Larsen scores were slightly but not significantly higher in the carrier group., Conclusion: The results of this study suggest that MEFV gene mutations appear to be an aggravating factor for the severity of RA, and consequently, patients with RA might be screened for MEFV gene mutations in countries where FMF is frequent. Whether the searching of MEFV gene mutations in RA patients is cost-effective deserves further investigations., (Copyright 2009 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: Systemic lupus erythematosus (SLE) patients have increased risk of coronary heart disease (CHD) that cannot be fully explained by the traditional risk factors. Metabolic alterations like oxidative stress and insulin resistance may be additional risk factors to contribute early and accelerated atherosclerosis in SLE. Our aim was to evaluate malondialdehyde (MDA) level, oxidative stress indicator, and homeostasis model assessment of insulin resistance (HOMA-IR), and possible relationship between oxidative stress and insulin resistance, in SLE., Methods: This cross-sectional controlled study included 30 SLE patients (SLE group) and 15 age- and sex-matched healthy controls (HC group). The SLE patients were classified into subgroups based on the disease activity index as active or inactive. Serum MDA, insulin, C-peptide, fasting blood glucose, lipid profile, acute phase reactants, tumor necrosis factor (TNF)-a, interleukin (IL)-6 and HOMA-IR were determined. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U and Pearson tests., Results: In the SLE group, TNF-a (7.9 [0.5-57.8] vs. 3.9 [0.3-6.3] pg/ml, p<0.01), IL-6 (9.2 [0.1-33.9] vs. 2.2 [0.1-4.8] pg/ml, p<0.01), MDA (2.3 [0.1-6.7] vs. 0.95 [0.5-2.96] nmol/ml, p<0.01) and C-peptide (1.9 [0.9-3.5] vs. 1.5 [1.1-2.4] ng/ml, p<0.01) levels were higher than in the HC group, while HOMA-IR index (1.7 [0.5-6.5] vs. 1.2 [0.8-2.9], p>0.05) was nonsignificantly higher. In the SLE group, MDA levels were correlated with insulin (r=0.614, p<0.05) and HOMA-IR (r=0.601, p<0.05)., Conclusion: In inflammatory diseases, relations between oxidative stress and insulin resistance, each of them triggers or enhances the other one, come to an impasse. In conclusion, this modifiable impasse might be important to prevent the development of atherosclerosis in SLE.

Background: Ghrelin is a powerful, endogenous orexigenic peptide. In addition, ghrelin has anti-inflammatory effects, and it has been reported that ghrelin down-regulates pro-inflammatory cytokines, including interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Obestatin appears to decrease food intake and appetite, and its potential role in inflammation is not yet clear. The aims of this study were to assess total and acylated (active) ghrelin and obestatin serum levels and their relations with inflammatory status in rheumatoid arthritis (RA) patients., Design: Fasting blood samples were obtained from 37 patients with RA, 29 patients with Behçet's disease (BD) and 28 healthy controls (HC). Total ghrelin and obestatin levels were measured by radioimmunoassay and acylated ghrelin was quantified by enzyme-linked immunosorbent assay., Results: Patients with RA had lower total ghrelin, but higher obestatin levels than patients with BD (p<0.05 for both), but when compared with HC group differences were not significant. There was no difference across groups in terms of acylated ghrelin. Total ghrelin level was not correlated with any study parameters in the all groups. Obestatin level correlated with erythrocyte sedimentation rate and DAS-28 in the RA group, the level of IL-6 in the BD group, and with the level of TNF-alpha in the HC group (r=0.400, p<0.05; r=0.412, p<0.05, r=0.543, p<0.01 and r=0.528, p<0.05, respectively)., Conclusions: Our results did not show a significant correlation between circulating ghrelin and clinical or laboratory markers of disease activity in RA. Surprisingly, obestatin correlated with some inflammatory markers. So, obestatin seems to be more valuable than ghrelin in the pathogenesis of RA.

Cardiac adverse effects of intravenous pulse methylprednisolone administration are well known, but there is little information about the cardiac side effects of oral methylprednisolone in the literature. We present a 41 year-old man with membranoproliferative glomerulonephritis in whom developed atrial fibrillation after oral methylprednisolone therapy.