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Öğe Apelin and fetuin-a may be subclinical inflammation biomarker in familial mediterranean fever: A pilot study(DERMAN MEDICAL PUBL, 2017) Sahin, Ali; Demirpence, Ozlem; Sahin, Mehtap; Bagci, Gokhan; Seven, Dogan; Dogan, Halef Okan; Camci, Ayse; Derin, Mehmet Emin; Bagci, BinnurAim: Positive acute-phase reactants generally increase during the attack period (AP) of familial Mediterranean fever (FMF) and return to normal range in the attack-free period (AFP). In some patients, the level of these acute-phase reactants does not decrease during the AFP, suggesting that subclinical vascular inflammation continues during the AFP. In the context of this Information, we tested whether apelin and fetuin-A can be used as inflammatory biomarkers in the AFP of FMF patients. Material and Method: Thirty FMF patients within AFP and thirty healthy subjects were included in this study. Serum apelin and fetuin-a levels were measured using enzyme-linked immunosorbent assay (ELISA) method. Results: The median levels of apelin were 113.07 +/- 15.9 ng/L in FMF and 307.82 +/- 52.76 ng/L in healthy subjects (p = 0.002). The median levels of fewin-A were 1352.2 +/- 127.61 ng/mL in the FMF group and 843.82 +/- 137.66 ng/mL in the control group (p= 0.009). In FMF patients, there was a significant correlation between apelin and fetuin-A levels (r=0.399; p =0.029). Furthermore, a significant inverse correlation was found between age and apelin (r= -0.499; p = 0.005), and a significant positive correlation was found between BMI and apelin (r = 0.769; p = 0.001). Additionally, a significant correlation was found between BMI and fetuin-A (r = 0.397; p = 0.030). Discussion: Lower serum apelin levels and higher fetuin-A levels were observed in FMF patients with AFP than in healthy subjects, suggesting that subclinical vascular inflammation continues during AFP in patients with FMF. Further studies with large study populations and different ethnic groups are necessary to show the role of apelin and fetuin-A in subclinical inflammation resulting from FMF.Öğe Can Calprotectin Show Subclinical Inflammation in Familial Mediterranean Fever Patients?(Korean Acad Medical Sciences, 2020) Asan, Gokmen; Derin, Mehmet Emin; Dogan, Halef Okan; Bayram, Meliha; Sahin, Mehtap; Sahin, AliBackground: Familial Mediterranean fever (FMF) is an autoinflammatory disease that has self-limiting inflammatory attacks during polyserositis. Hepcidin is a protein, and interleukin-6 stimulation increases hepcidin levels. Calprotectin (CLP) is a recently defined cytokine released from monocytes and neutrophils in response to tissue trauma and inflammation. There are studies in the literature showing that it can be used as a biomarker in rheumatic diseases such as ankylosing spondylitis and rheumatoid arthritis. Here, we compared the levels of hepcidin and CLP in healthy individuals and FMF patients during an attack-free period and show its relation to genetic mutations. Methods: This is a cross-sectional study. Between July 2017 and December 2017, 60 patients diagnosed with FMF an admitted to the Cumhuriyet University Faculty of Medicine Department of Internal Medicine Rheumatology as well as 60 healthy volunteers without any rheumatic, systemic, or metabolic diseases were enrolled in this study. Blood was collected from a peripheral vein to measure serum CLP and hepcidin levels. Blood tests were examined by ELISA; the study protocol was approved by the local ethics committee. Results: Median serum hepcidin level was 468.1 (210.3-807.8) pg/mL in FMF group and 890.0 (495.0-1,716.9) pg/mL in the healthy control (HC) group. There was a statistically significant difference between the two groups (P< 0.001). The median serum levels of CLP in the FMF group were measured as 1,331.4 (969.34,584.6 pg/mL and 73.8(45.0-147.9) pg/mL in the HC group. There was a statistically significant difference between the two groups (P < 0.001). Receiver operating characteristic analysis showed that the sensitivity was 66.7% and the specificity was 71.7% at serum hepcidin < 581.25 pg/mL (P< 0.05); the sensitivity was 96.7% and specificity was 100% at CLP > 238 pg/mL (P < 0.05). There was no significant difference between serum hepcidin and CLP levels in FMF patients with M694V homozygous and M694V heterozygous (P> 0.05). There was no significant difference in serum hepcidin levels between FMF patients with and without arthritis, proteinuria, and amyloidosis (P < 0.05). There was no significant correlation between laboratory findings, gender, age, and serum CLP and hepcidin levels (P> 0.05, r< 0.25). Conclusion: Serum CLP levels in FMF patients during an attack-free period are significantly higher than in the HC groups. Serum hepcidin levels in FMF patients are significantly lower than in the HC group. Low levels of hepcidin may be explained by including FMF patients during an attack-free period in the study. CLP may be an important biomarker in FMF. A better understanding of the role of these biomarkers in the diagnosis of FMF is needed to evaluate the results in a more comprehensive way.Öğe Comparison of Serum Hepcidin and Calprotectin Levels in Patients with Familial Mediterranean Fever (FMF) and Healthy Subjects(WILEY, 2018) Asan, Gokmen; Derin, Mehmet Emin; Dogan, Halef Okan; Bayram, Meliha; Sahin, Mehtap; Sahin, Ali…Öğe The Effects of the Jak-Stat Signal Pathway Inhibition on Collagen Biosynthesis in Fibroblast Cell Culture(WILEY, 2018) Sahin, Mehtap; Aydin, Huseyin; Altun, Ahmet; Derin, Mehmet Emin; Sahin, Ali…Öğe Evaluation of Prolidase and HIF-1 alpha Levels in Patients with Familial Mediterranean Fever (FMF)(WILEY, 2018) Bayram, Meliha; Derin, Mehmet Emin; Dogan, Halef Okan; Asan, Gokmen; Sahin, Mehtap; Sahin, Ali…Öğe High prolidase levels in patients with Familial Mediterranean Fever (FMF)(Sciendo, 2020) Bayram, Meliha; Derin, Mehmet Emin; Dogan, Halef Okan; Asan, Gokmen; Sahin, Mehtap; Sahin, AliIntroduction. Familial Mediterranean Fever (FMF) is an autoinflammatory disease. Prolidase is a specific imidodipeptidase that plays a role in collagen degradation, and an important role in inflammation and wound healing. Hypoxia-inducible factor-1 alpha (HIF-1) is an important protein in the regulation of immunological response, hemostasis, vascularization. The aim of the study was to compare serum prolidase and HIF-1 alpha levels in patients with FMF in attack-free period and healthy control group. Methods. Between August 2017 and December 2017, sixty patients diagnosed with FMF according to the criteria of the Tel-hashomer and admitted to Sivas Cumhuriyet University Medical Faculty, Internal Medicine Rheumatology Department and sixty healthy volunteers were enrolled in the study. Results. Median serum prolidase levels were 72.1 (25.1-114.9) ng/ml in FMF group and 30.7 (21.3-86.2) ng/mL in healthy control (HC) group (p = 0.018). ROC analysis showed that the sensitivity was 65% and the specificity was 68.3% at serum prolidase levels 54.03 ng/mL (p < 0.05). The median serum levels of HIF-1 alpha in the FMF group was 482.0 (292.0-3967.0) pg/mL and 632.0 (362.0-927.0) pg/mL in the HC group (p > 0.05). There was no significant correlation between laboratory findings, sex, age, and prolidase (p > 0.05). Conclusion. Serum prolidase enzyme levels in FMF patients with attack-free period were significantly higher than in the HC group. However, the role of prolidase and HIF1-alpha in the FMF disease needs to be clarified with more extensive and comprehensive studies.Öğe Presepsin Levels of Patients with Crimean-Congo Hemorrhagic Fever(NATL INST INFECTIOUS DISEASES, 2016) Demirpence, Ozlem; Dogan, Halef Okan; Ersan, Serpil; Sahin, Mehtap; Sahin, Hasan; Bakir, MehmetLevels of presepsin (a soluble cluster of differentiation subtype 14 [CD14]) are thought to increase in cases of bacterial infection. CD14 has also been found to play a role in the pathogenesis of various viral diseases. Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral infection. Our study focuses on presepsin levels as a biomarker for CCHF. Serum presepsin levels in a CCHF group (n = 59) and control group (n = 28) were compared. Patients with CCHF were classified according to severity grading score as having mild, moderate, or severe infection and were allocated to corresponding subgroups (groups 1, 2, and 3, respectively). Presepsin levels were measured in serum samples by using a commercial enzyme-linked immunosorbent assay kit. The mean presepsin levels in the CCHF group as a whole and the healthy group were found to be significantly different (1,499.46 +/- 411.96 pg/ml and 430.68 +/- 61.21 pg/ml, respectively). The mean presepsin levels of the CCHF subgroups (1, 2 and 3) and the healthy group were also found to be significantly different (1,204.53 +/- 371.18, 1,464.21 +/- 338.37, 2,007.36 +/- 82.18, and 430.68 +/- 61.21 pg/ml, respectively) (p < 0.05). We also found that as the severity of the disease increased, the presepsin level also increased. We postulate that the presepsin levels could be used as a supportive biomarker for diagnosis and follow-up of the disease.Öğe The Effects of Tofacitinib-Mediated Janus Kinase/Signal Transducers and Activators of the Transcription Signal Pathway Inhibition on Collagen Biosynthesis in Hepatic and Skin Fibroblast Celt Culture(Turkish League Against Rheumatism, 2020) Sahin, Mehtap; Aydin, Huseyin; Altun, Ahmet; Derin, Mehmet Emin; Sahin, AliObjectives: This study aims to investigate the effects of Janus kinase/signal transducers and activators of the transcription (JAK/STAT) pathway inhibition on collagen biosynthesis in fibroblast cell culture by tofacitinib. Materials and methods: BJ-CRL-1474 (R) (skin) and BRL3A (R) (hepatic) fibroblast cell cultures were proliferated in a suitable medium. Tofacitinib was administered to fibroblast cells proliferating in 96-well flasks at concentrations of 25, 50, 100, 200, 400, and 800 nM. Tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-3 (MMP-3), transforming growth factor beta 1 (TGF-beta 1), and hydroxyproline levels were measured using the enzyme-linked immunosorbent assay method. Results: Tofacitinib showed cytotoxic effect on skin and liver cell culture. The cytotoxic effect of tofacitinib started at 100 nM (p<0.05). The highest effect was obtained at 800 nM. The time-dependent cytotoxic effect of tofacitinib was significantly higher at all concentrations after 72 hours than at 24 and 48 hours (p<0.05). The level of TGF-beta 1 was significantly lower even at a tofacitinib concentration of 25 nM (p<0.05). There were significant decreases in MMP-3, TIMP-1, and hydroxyproline levels after tofacitinib administration (p<0.05). Conclusion: Tofacitinib inhibited fibroblast cell proliferation in a concentration-dependent manner in a fibroblast cell culture. However, further extensive animal and human studies are necessary to determine the clinical significance of this effect.
