Publications

  • 1.84
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    Evaluation of Early Atherosclerosis in Patients with Inflammatory Bowel Disease.

    Hasan Kayahan, Ismail Sari, Nesat Cullu, Fahize Yuksel, Serdal Demir, Mesut Akarsu, Yigit Goktay, Belkis Unsal, Hale Akpinar

    Digestive diseases and sciences. 04/2012;

    BACKGROUND: Data regarding early atherosclerosis and inflammatory bowel disease are limited and conflicting results are present. AIMS: The purpose of this study was to evaluate serological and sonographical evidence of subclinical vascular involvement in patients with inflammatory bowel disease. MET... [more] BACKGROUND: Data regarding early atherosclerosis and inflammatory bowel disease are limited and conflicting results are present. AIMS: The purpose of this study was to evaluate serological and sonographical evidence of subclinical vascular involvement in patients with inflammatory bowel disease. METHODS: Thirty-nine patients with inflammatory bowel disease (20 Crohn's disease, and 19 ulcerative colitis patients) and 31 healthy controls were consecutively enrolled in the study. Flow mediated dilatation of the brachial artery and intima media thickness assessments of the common carotid artery were measured sonographically. Soluble CD40 ligand levels were evaluated. Crohn's disease activity index and modified Truelove-Witt's criteria were also noted. RESULTS: Age, sex distribution, serum lipids, smoking status, and intima media thickness of the common carotid artery were similar between the inflammatory bowel disease patients and controls (p > 0.05). However, both endothelium dependent and independent flow mediated dilatation values were significantly impaired in the inflammatory bowel disease group compared with healthy controls (p < 0.05). Erythrocyte sedimentation rate, C-reactive protein and soluble CD40 ligand values were significantly increased in inflammatory bowel disease patients compared with controls (p < 0.05), and soluble CD40 ligand was negatively correlated with flow mediated dilatation (r = -0.3, p < 0.05). Flow mediated dilatation was significantly predicted from the concentrations of C-reactive protein and soluble CD40 ligand. CONCLUSION: Functional atherosclerosis is present in inflammatory bowel disease before early structural changes occur in vasculature. Higher sCD40L may indicate worse vascular outcome for IBD.
  • The effect of non-steroidal anti-inflammatory drugs on the endothelial function of patients with osteoarthritis in short term.

    Dilek Solmaz, Ismail Sari, Gercek Can, Servet Akar, Isin Ceylan, Mustafa Secil, Nurullah Akkoc

    International journal of rheumatic diseases. 04/2012; 15(2):207-11.

    Objective:  Our primary aim was to test whether non-steroid anti-inflammatory drug (NSAID) use may account for endothelial dysfunction (ED) in the acute period. Additionally, we also aimed to compare the effect of diclofenac and naproxen on endothelial function. Methods:  Forty patients with osteoar... [more] Objective:  Our primary aim was to test whether non-steroid anti-inflammatory drug (NSAID) use may account for endothelial dysfunction (ED) in the acute period. Additionally, we also aimed to compare the effect of diclofenac and naproxen on endothelial function. Methods:  Forty patients with osteoarthritis (OA) were included in the study. Subjects currently receiving NSAIDs were asked to discontinue their anti-inflammatory medications (for at least 5 days) before the study. After the wash-out period, all subjects underwent vascular ultrasound measurements. Following baseline vascular imaging, patients were randomly assigned in a 1 : 1 ratio to receive either diclofenac (75 mg twice daily, n = 20), or naproxen (500 mg twice daily, n = 20) for 7 days. Endothelial function was evaluated by using the flow-mediated dilatation (FMD) method, at baseline, and after 1 week of NSAID treatment. Results:  There were 40 OA patients (4 male, 36 female). The median age of the patients was 60 ± 14 years. There were equal numbers of subjects in each treatment group. Age, sex distribution, body mass index, serum lipids, erythrocyte sedimentation rate, C-reactive protein and fasting glucose levels were similar between the diclofenac and naproxen groups (P > 0.05). The brachial artery diameter (BAD), endothelium-dependent vasodilatation (FMD%) and nitroglycerin-induced endothelium-independent vasodilatation (NTG%) values were not different between pretreatment and on the seventh day in the NSAID treatment groups (P > 0.05). Subgroup analysis also showed similar values of BAD, FMD%, and NTG% between naproxen and diclofenac groups (P > 0.05). Conclusion:  Our results suggest that nonselective cyclo-oxygenase antagonists naproxen and diclofenac have no effect on endothelial function during short-term use.
  • 3.85
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    Evaluation of circulating endothelial and platelet microparticles in men with ankylosing spondylitis.

    Ismail Sari, Giray Bozkaya, Halil Kirbiyik, Ahmet Alacacioglu, Halil Ates, Gulten Sop, Gercek Can, Ali Taylan, Ozden Piskin, Yasar Yildiz, Nurullah Akkoc

    The Journal of rheumatology. 03/2012; 39(3):594-9.

    To evaluate the profiles of endothelial microparticles (EMP) and platelet microparticles (PMP) in men with ankylosing spondylitis (AS) and healthy subjects. We also aimed to determine whether microparticles (MP) correlate with disease activity, function, and spinal mobility indices. There were 82 me... [more] To evaluate the profiles of endothelial microparticles (EMP) and platelet microparticles (PMP) in men with ankylosing spondylitis (AS) and healthy subjects. We also aimed to determine whether microparticles (MP) correlate with disease activity, function, and spinal mobility indices. There were 82 men with AS and 53 healthy controls. Subjects with a history of chronic diseases including coronary artery disease, hypertension, diabetes mellitus, and dyslipidemia were excluded. MP were stained with monoclonal antibodies against platelets and endothelial cells and quantified using flow cytometry. MP that were positive for both CD42a+/CD31+ and total CD42a+ were identified as PMP; and MP consisting of CD42a-/CD31+ and total CD144+ were considered EMP. EMP and PMP were similar between the patient and control groups (p > 0.05). Comparison of patients with AS in the active disease state (BASDAI ≥ 4) and in the inactive state showed that EMP and PMP were not different between the groups (p > 0.05). Correlation analysis revealed no correlation with Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, or Bath Ankylosing Spondylitis Metrology Index. C-reactive protein was significantly correlated with PMP and CD42a-/CD31+ EMP (p < 0.05). Comparison of patients with AS treated with anti-tumor necrosis factor (anti-TNF) drugs, subjects treated conventionally, and healthy controls revealed that PMP and CD42a-/CD31+ EMP were significantly downregulated in patients receiving biological agents. Circulating EMP and PMP, known to be indicators and mediators of vascular injury, were not significantly altered in men with AS who did not have classical cardiovascular risk factors. Significantly downregulated MP in patients receiving biological agents suggested that anti-TNF treatment may have a beneficial effect on vascular function in AS.
  • 1.64
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    The Effect of Regular Colchicine Treatment on Biomarkers Related with Vascular Injury in Newly Diagnosed Patients with Familial Mediterranean Fever.

    Ismail Sari, Arif Yuksel, Didem Kozaci, Sema Selcuk, Goksel Gokce, Yasar Yildiz, Hakan Demirel, Gulten Sop, Ahmet Alacacioglu, Necati Gunay, Nurullah Akkoc

    Inflammation. 01/2012;

    We aimed to evaluate some of the vascular biomarkers in newly diagnosed, colchicine naive familial Mediterranean fever (FMF) patients. Our primary aim was to investigate the effect of regular colchicine treatment on these variables. Twenty-four (12 males [M] and 12 females [F], 33.3 ± 13.4 years) ne... [more] We aimed to evaluate some of the vascular biomarkers in newly diagnosed, colchicine naive familial Mediterranean fever (FMF) patients. Our primary aim was to investigate the effect of regular colchicine treatment on these variables. Twenty-four (12 males [M] and 12 females [F], 33.3 ± 13.4 years) newly diagnosed FMF patients were included in the study. These patients were started on colchicine treatment following the initial assessment and were studied again no earlier than 2 months. Five patients were lost to follow-up, and assessment of the on-treatment patients was performed on the remaining 19 patients (8 M and 11 F, 33.6 ± 11.8 years). There were 19 healthy subjects (11 M and 8 F, 32.2 ± 7.2 years) who served as a control group. Cellular adhesion molecules (CAMs; soluble intercellular adhesion molecule-1 [sICAM-1] and soluble CD146 [sCD146]), plasminogen activator inhibitor-1 (PAI-1), fetuin-A and hs-CRP were studied. Examinations were performed on attack-free periods. The levels of hs-CRP, fetuin-A, sICAM-1, and PAI-1 were significantly higher in newly diagnosed patients compared to those of controls (P < 0.05). All studied parameters were significantly downregulated after regular colchicine therapy (P < 0.05). Comparison of on-treatment data with controls showed that the levels of the vascular biomarkers, except sCD146, were similar between the groups (P > 0.05). On-treatment sCD146 was found significantly lower than the controls (P < 0.05). In regression analysis, none of the independent variables in the model significantly predicted the vascular biomarkers (P > 0.05). Administration of therapeutic doses of colchicine markedly reduces vascular injury parameters and normalizes the values in FMF.
  • 0.94
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    Comparative levels of macrophage migration inhibitory factor, procalcitonin, osteoprotegerin, interleukin-8, hs-C reactive protein, d-dimer in febrile neutropenia, newly diagnosed cancer patients, and infectious fever.

    Oktay Bilgir, Ferda Bilgir, Levent Kebapcilar, Giray Bozkaya, Mehmet Calan, Halil Kırbıyık, Meltem Avci, Ismail Sari, Arif Yuksel, Tolgay Isikyakar

    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 11/2011; 46(1):19-24.

    The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and d-dimer during fever above 38.3°C due to various causes. Blood samples taken from a total of consecutive 65 hospitalized ... [more] The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and d-dimer during fever above 38.3°C due to various causes. Blood samples taken from a total of consecutive 65 hospitalized patients during fever were prospectively tested for hsCRP, PCT, IL-8, OPG, MIF and d-dimer. Of these patients, there were 26 patients presenting with chemotherapy-induced neutropenia who had no infectious agents found; 23 patients, who had a malignancy with a febrile episode which was neither a microbiologically documented infection nor a chemotherapy-induced neutropenia, and 16 patients who did not have a malignancy and were considered to have a clinically and microbiologically documented infection. IL-8 and d-dimer levels were higher in patients with febrile neutropenia than in the other two groups. Although MIF and OPG were higher in patients with newly diagnosed cancers, there were no differences among the three groups regarding PCT and hs-CRP values. High serum IL-8 and d-dimer levels can be useful markers to identify hospitalized chemotherapy-induced neutropenia patients. MIF and OPG were found to be higher in patients with newly diagnosed cancer.
  • 1.49
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    Down-regulation of adiponectin in patients with familial Mediterranean fever during attack-free period.

    Vedat Gerdan, Ismail Sari, Didem Kozacı, Fatos Onen, Feride Yüksel, Ozgül Soysal, Dilek Solmaz, Necati Günay, Nurullah Akkoc, Servet Akar

    Rheumatology international. 08/2011;

    To evaluate the circulating levels of adipokines (leptin and adiponectin) and ghrelin in patients with familial Mediterranean fever (FMF) and also to assess the relationships between these molecules and disease-related parameters. Forty-eight FMF patients in attack-free period (31 men, [M], 17 women... [more] To evaluate the circulating levels of adipokines (leptin and adiponectin) and ghrelin in patients with familial Mediterranean fever (FMF) and also to assess the relationships between these molecules and disease-related parameters. Forty-eight FMF patients in attack-free period (31 men, [M], 17 women, [F], mean age 35.8 ± 8.6 years, and a mean body mass index [BMI] of 24.7 ± 3.1) and 40 age-, sex-, and BMI-matched healthy controls (24 M, 16 F, mean age 35.5 ± 8.5 years, and a mean BMI of 24.5 ± 2.8) were included in the study. Patients and controls with a history of any other chronic diseases and obese or underweight subjects were excluded. High-sensitive C-reactive protein (hs-CRP), leptin, adiponectin, and total ghrelin concentrations were studied. Age, sex, BMI, waist circumference, and smoking status were similar between FMF patients and controls (P > 0.05). Adipose tissue-derived molecules including leptin, and adiponectin were lower than healthy controls but only adiponectin levels reached the statistically significance (16.7 ± 8.9 ng/ml vs. 27.7 ± 15.9 ng/ml, P < 0.001) and leptin concentrations just missed significance (25.2 ± 16.2 ng/ml vs. 34.9 ± 27.2 ng/ml, P = 0.051). Ghrelin concentrations were not different between the groups. Adiponectin levels were significantly and negatively correlated with hs-CRP (P < 0.05, r = -0.24). The results of this study suggest that low-grade chronic inflammation during attack-free period in FMF patients may suppress adiponectin production or low levels of adiponectin might contribute to subclinical inflammation in these patients.
  • 1.49
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    Evaluation of the T helper 17 axis in ankylosing spondylitis.

    Ali Taylan, Ismail Sari, Didem L Kozaci, Arif Yuksel, Safak Bilge, Yasar Yildiz, Gulten Sop, Isil Coker, Necati Gunay, Nurullah Akkoc

    Rheumatology international. 07/2011;

    To evaluate the T helper 17 (Th17) axis and its relation to tumor necrosis factor (TNF) alpha blockage and disease activity in ankylosing spondylitis (AS). The study included 127 AS patients (100M/27F) and 38 (27M/11F) controls. Spinal mobility was assessed by the bath ankylosing spondylitis metrolo... [more] To evaluate the T helper 17 (Th17) axis and its relation to tumor necrosis factor (TNF) alpha blockage and disease activity in ankylosing spondylitis (AS). The study included 127 AS patients (100M/27F) and 38 (27M/11F) controls. Spinal mobility was assessed by the bath ankylosing spondylitis metrology index (BASMI). Patients were also evaluated with the bath ankylosing spondylitis functional (BASFI) and bath ankylosing spondylitis disease activity index. Cytokines including IL-6, IL-12, TGF-β, IL-17A, and IL-23 were measured in serum sample using commercially available ELISA kits. Cytokines including IL-6, IL-12, TGF-β, IL-17, and IL-23 were significantly higher in the AS patients than the controls (P < 0.05). The Th-17-related cytokines were not different between patients treated with anti-TNF and conventional therapies (P > 0.05). Cytokines were also similar between patients with active and inactive disease (P > 0.05). On correlation analysis, IL-17 was correlated with IL-23 and IL-12 (P < 0.05) and IL-23 showed correlations with IL-12 and BASMI (P < 0.05). We found serum levels of Th-17-related cytokines to be significantly increased in the sera of AS patients. Disease activity and treatment type did not affect the level of these cytokines.
  • 0.94
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    Comparison of conventional dose steroid treatment and high dose steroid treatment as run-in regime for splenectomy in immune thrombocytopenic purpura (ITP).

    Oktay Bilgir, Ferda Bilgir, Levent Kebapcilar, Giray Bozkaya, Mehmet Çalan, Halil Kirbiyik, Meltem Avci, Ismail Sari, Arif Yuksel, Tolgay Isikyakar

    Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 06/2011; 44(3):239-42.

    Splenectomy is a treatment procedure for ITP which is being used for more that 50years and is still considered as the best option for the treatment of the condition. The facts that frequent monitoring is not required and that medical treatment is not indicated following splenectomy in most cases are... [more] Splenectomy is a treatment procedure for ITP which is being used for more that 50years and is still considered as the best option for the treatment of the condition. The facts that frequent monitoring is not required and that medical treatment is not indicated following splenectomy in most cases are among the major advantages of the procedure. To compare the conventional dose steroid and high dose steroid treatments as run-in regime for splenectomy in patients diagnosed with ITP. The conventional dose steroid (1mg/kg, n=20) and high dose steroid treatments (30mg/kg, n=30) were applied to 50 cases with ITP between 1998 and 2008 in our clinic. High dose steroid produced higher platelet count on days 3, 5, and 7 compared to conventional dose steroid. There were no differences between the groups in terms of adverse effects. Treatments were discontinued after the operation by rapidly reducing the dose. Postoperative values regarding response to splenectomy were comparable in both groups. Both higher and earlier responses obtained with high dose steroid may be significant in reducing hospitalization period of patients and eliminating life-threatening platelet values within the shortest time possible.
  • 1.67
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    Evaluation of various endothelial biomarkers in ankylosing spondylitis.

    Ali Taylan, Ismail Sari, Didem L Kozaci, Yasar Yildiz, Safak Bilge, Isil Coker, Sergir Maltas, Necati Gunay, Nurullah Akkoc

    Clinical rheumatology. 05/2011; 31(1):23-8.

    Atherosclerosis has been shown to be increased in chronic inflammatory diseases including ankylosing spondylitis (AS). Impaired endothelial function, the first step in atherosclerosis, may be reflected by changes in various endothelial biomarkers of hemostasis and the release of several cellular adh... [more] Atherosclerosis has been shown to be increased in chronic inflammatory diseases including ankylosing spondylitis (AS). Impaired endothelial function, the first step in atherosclerosis, may be reflected by changes in various endothelial biomarkers of hemostasis and the release of several cellular adhesion molecules or cytokines. In this study, we investigated changes in the levels of various possible markers with regard to disease activity and treatment regimen with/without anti-TNF-α drugs. Fifty-six AS patients (44 males) and 27 controls (19 males) with no known cardiovascular risk factors were included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index, and patients were evaluated with the Bath Ankylosing Spondylitis Functional Index and the Bath Ankylosing Spondylitis Disease Activity Index. Cytokines and various endothelial biomarkers were measured in serum samples using commercially available ELISA kits. Age, sex, BMI, waist circumference, fasting glucose, MAP, lipids are all similar between patients and controls. von Willebrand factor (vWF), soluble thrombomodulin (sTM), and urotensin (UT-II) were found to be significantly higher in the sera of the patients compared to the controls. Treatment with anti-TNF-α compared to conventional therapy and disease activity in AS patients seemed to have no effect on the blood levels of UT-II, sTM, CD146, vWF, plasminogen activator inhibitor-1, tissue plasminogen activator, or the thrombin-antithrombin complex. The increased UT-II, sTM, and vWF in AS patient sera regardless of treatment and disease activity suggest an increased tendency for atherosclerosis.
  • 1.67
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    Mediterranean fever (MEFV) gene mutation frequency is not increased in adults with rheumatic heart disease.

    Ismail Simsek, Cem Koz, Nurcan Basar, Ismail Sari, Hakan Erdem, Salih Pay, Bunyamin Kisacik, Muhterem Bahce, Ayhan Dinc

    Clinical rheumatology. 04/2011; 30(4):491-5.

    It is well established that there are people with higher risk of developing acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Mediterranean fever (MEFV) gene mutations might be one of the genetic predisposition factors in the development of ARF/RHD since defect in familial Mediterranean... [more] It is well established that there are people with higher risk of developing acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Mediterranean fever (MEFV) gene mutations might be one of the genetic predisposition factors in the development of ARF/RHD since defect in familial Mediterranean fever (FMF) patients is proposed to be heightened inflammatory response to certain stimuli. Previous clinical observations suggested a relationship between FMF and ARF/RHD. The aim of this study was to investigate the role of the MEFV gene mutations in the susceptibility to RHD in Turkish patients. A total of 100 patients with RHD and 100 healthy controls were included in the study. Diagnosis of RHD was based on echocardiographic findings in which a predominant mitral stenosis was used as an inclusion criterion. Genetic analysis was carried out by sequence analysis investigating two hot spots (exons 2 and 10) for MEFV mutations. Mutation analysis showed that 22 RHD patients (22%) and 24 healthy controls (24%) carried at least one mutated allele. MEFV mutations were identified in 22 of 200 (11%) chromosomes in RHD patients while 26 of the 200 (13%) chromosomes of healthy controls were found to carry a mutated allele. No difference was found in allele frequencies and their distribution between the patients and healthy controls (p = 0.54). MEFV mutations are not associated with a predisposition to develop RHD in adult Turkish patients.
  • 1.36
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    Metformin plus oral contraceptive may decrease plasma sCD40 ligand in women with PCOS patients.

    Levent Kebapcilar, Ayse Gul Kebapcilar, Oktay Bilgir, Cuneyt Eftal Taner, Giray Bozkaya, Yasar Yildiz, Ismail Sari

    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 02/2011; 27(2):91-5.

    To evaluate sCD40L levels in women with polycystic ovary syndrome (PCOS) who use combination therapy with metformin and oral contraceptives. Total of 60 patients with PCOS was studied to evaluate and compare with a non-PCOS group consisting of 30 subjects. A low-dose oral contraceptive containing et... [more] To evaluate sCD40L levels in women with polycystic ovary syndrome (PCOS) who use combination therapy with metformin and oral contraceptives. Total of 60 patients with PCOS was studied to evaluate and compare with a non-PCOS group consisting of 30 subjects. A low-dose oral contraceptive containing ethinyl oestradiol-cyproterone acetate (EE/CA) and metformin (M; 850 mg metformin twice a day) were given for three cycles. Plasma sCD40L was measured before and after the treatment of 3 months. At baseline, the sCD40L levels of the patients with PCOS was significantly higher than those of control subjects (3.1 ± 2.0 vs. 2.05 ± 1.0, respectively; p=0.002). An average of 3 months of EE/CA-M therapy induced a significant decrease of sCD40L levels in the PCOS group (3.1 ± 2.0 vs. 2.5 ± 1.0; p=0.026). After having treated patients with PCOS, the sCD40L level was not completely normalised when compared to the healthy controls (2.5 ± 1.0 vs. 2.05 ± 1.0; p=0.039). PCOS is associated with elevated levels of sCD40L. Adding metformin therapy to EE/CA may decrease sCD40L levels in women PCOS. However, after the treatment for PCOS subjects, the sCD40L was not completely normalised when compared patients to healthy controls.
  • 1.04
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  • 1.13
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    The effect of iron treatment on adhesion molecules in patients with iron deficiency anemia.

    Arif Yuksel, Levent Kebapcilar, Erkan Erdur, Giray Bozkaya, Ismail Sari, Ahmet Alacacioglu, Ayse Gul Kebapcilar, Gulten Sop

    Biological trace element research. 12/2010; 137(3):317-23.

    The present study was aimed to determine the effect of iron supplementation on levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with iron deficiency anemia (IDA). In this study, 26 female patients diagnosed with iron de... [more] The present study was aimed to determine the effect of iron supplementation on levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with iron deficiency anemia (IDA). In this study, 26 female patients diagnosed with iron deficiency were treated approximately 3 months of oral iron supplementation (99 ± 10 days; ferrous glycine sulfate; 100 mg/day of elemental iron). Levels of sICAM-1 and sVCAM-1 were assessed prior to treatment and after approximately 3 months of treatment and compared with 26 healthy female subjects. A significant increase in sVCAM levels was found in the patients with iron deficiency at the end of the treatment relative to pretreatment levels compared to controls, whereas no significant differences were determined in sICAM levels. In the posttreatment period, no significant change was observed in sICAM levels compared to the pretreatment levels, whereas sVCAM levels decreased. However, after the treatment period, the sVCAM, hemoglobin, mean corpuscular volume (MCV), and serum ferritin levels did not return to the normal range compared to the controls. Pretreatment sVCAM-1 levels were inversely correlated with levels of hemoglobin, hemotocrit, MCV, serum iron, and ferritin. After treatment, the sVCAM-1 levels were negatively correlated with ferritin levels. Levels of sVCAM were significantly higher in patients with IDA than controls. After the treatment period, the sVCAM levels were not completely normalized in patients with IDA compared to controls, regardless of the presence of inadequate levels of hemoglobin, MCV, and serum ferritin. Thus, iron supplementation not only ameliorates anemia, but may also reduce the inflammation markers in cases with IDA.
  • 4.15
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    Increased prevalence of M694V in patients with ankylosing spondylitis: additional evidence for a link with familial mediterranean fever.

    Nurullah Akkoc, Ismail Sari, Servet Akar, Omer Binicier, Mark G Thomas, Michael E Weale, Merih Birlik, Yusuf Savran, Fatos Onen, Neil Bradman, Christopher A Plaster

    Arthritis and rheumatism. 10/2010; 62(10):3059-63.

    To assess whether there is a statistically significant difference in the frequency of common MEFV allele variants in patients with ankylosing spondylitis (AS) as compared with control patients with rheumatoid arthritis (RA) and with healthy control subjects. Sixty-two patients with AS, 50 healthy co... [more] To assess whether there is a statistically significant difference in the frequency of common MEFV allele variants in patients with ankylosing spondylitis (AS) as compared with control patients with rheumatoid arthritis (RA) and with healthy control subjects. Sixty-two patients with AS, 50 healthy control subjects, and 46 patients with RA were assessed for the presence of MEFV variants. Exon 10 was analyzed by direct sequencing. E148Q was analyzed by restriction endonuclease enzyme digestion (REED) or by direct sequencing when REED analysis failed. The allele frequency of all MEFV variants in the AS group was significantly higher than that in the pooled control group of healthy subjects plus RA patients (15.3% versus 6.8%; P = 0.021). M694V was the only variant that was significantly more common in the AS group than in the combined or individual control groups (P = 0.026 for AS patients versus healthy controls, P = 0.046 for AS patients versus RA patient controls, and P = 0.008 for AS patients versus healthy and RA patient control groups). The carriage rate of M694V was also significantly higher in the AS patient group than in the combined control group (odds ratio 7.0, P = 0.014). Neither M694V nor any other MEFV variant showed a correlation with most of the disease-related measures examined. We found an increased frequency of MEFV variants in AS patients as compared with healthy controls and with RA patient controls. This was primarily due to the presence of M694V. The roles of other exon 10 variants, as well as the relationship between the variant status and the severity and clinical course of the disease, need to be explored in further studies that include sufficiently large sample sizes.
  • Fetuin-A and interleukin-18 levels in ankylosing spondylitis.

    Ismail Sari, Levent Kebapcilar, Ali Taylan, Oktay Bilgir, Didem L Kozaci, Yasar Yildiz, Arif Yuksel, Necati Gunay, Nurullah Akkoc

    International journal of rheumatic diseases. 02/2010; 13(1):75-81.

    Interleukin-18 (IL-18) and fetuin-A have been implicated in atherosclerosis. Preliminary evidence suggests that ankylosing spondylitis (AS) is associated with an increased risk of atherosclerosis. The aim of the present study was to investigate possible abnormalities in IL-18 and fetuin-A levels in ... [more] Interleukin-18 (IL-18) and fetuin-A have been implicated in atherosclerosis. Preliminary evidence suggests that ankylosing spondylitis (AS) is associated with an increased risk of atherosclerosis. The aim of the present study was to investigate possible abnormalities in IL-18 and fetuin-A levels in AS. Subjects without established cardiovascular (CV) risk factors were studied. Fasting glucose, serum lipids, high sensitive C-reactive protein (hsCRP), erythrocyte sedimentation rate, IL-18 and fetuin-A were assessed. Patients were also evaluated with the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Disease Activity Index. Fourty-five patients with AS (37.4 +/- 9.7 years; 35M/10F) and 29 controls (35.5 +/- 11.1 years; 21M/8F) were studied. Fetuin-A levels were significantly higher in AS patients compared to controls (1023.5 +/- 171.6 vs. 856.9 +/- 207.9 microg/mL, P < 0.001). IL-18 levels were also higher in the AS group but the difference was not significant (184 +/- 186 vs. 140 +/- 115, P = 0.1). Significant but weak correlations were found between fetuin-A, IL-18, hsCRP, low density lipoprotein cholesterol, and triglyceride levels (P < 0.05; r = 0.4, 0.3, 0.2, and 0.3 respectively). Comparison of subjects with respect to the treatment type, disease activity and history of peripheral arthritis yielded no difference regarding fetuin-A and IL-18 between groups. Fetuin-A and IL-18 levels seem to be increased in AS patients regardless of disease activity and treatment type.
  • 1.04
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    Subclinical hypercortisolism among polycythemia vera patients.

    Oktay Bilgir, Levent Kebapcilar, Inci Alacacioglu, Ferda Bilgir, Yasar Yildiz, Arif Yuksel, Ismail Sari

    Internal medicine (Tokyo, Japan). 01/2010; 49(13):1277-80.

    JAK2V617F, a somatic gain-of-function mutation involving the JAK2 tyrosine kinase gene, occurs in nearly all patients with polycythemia vera (PV). JAK2 is also essential in hypothalamo-pituitary-adrenal (HPA) axis system which is known to play a role in subsequent steroid secretion. The purpose of t... [more] JAK2V617F, a somatic gain-of-function mutation involving the JAK2 tyrosine kinase gene, occurs in nearly all patients with polycythemia vera (PV). JAK2 is also essential in hypothalamo-pituitary-adrenal (HPA) axis system which is known to play a role in subsequent steroid secretion. The purpose of this study was to determine whether or not PV induces subclinical hypercortisolism (SH). Cross-sectional study. In order to compare the prevalence of SH in PV and matched control individuals, we performed a case-controlled study, enrolling 31 PV and 20 age- and body mass index-matched patients. Adrenal endocrine function was assessed in a cohort of 31 patients with PV. Baseline serum cortisol levels and 2-day 2 mg DST (dexamethasone suppression test, 0.5 mg dexamethasone orally every 6 hours for two days) showed a trend for higher serum cortisol levels in PV patients than in control subjects. Among the 31 patients, 6 had biological abnormality of the hypothalamic-pituitary-adrenal axis and were diagnosed as subclinical hypercortisolism. None of the subjects in the control group exhibited cortisol responses to DST higher than 50 nmol/L. In conclusion, a relatively high prevalence of hypercortisolism was found in PV patients. As these observations were in a small cohort of PV, further studies are needed to evaluate HPA axis in PV patients.
  • [Serum levels of macrophage migration inhibitory factor and leptin in patients with acute trichinellosis].

    Leyla Didem Kozaci, Ismail Sari, Servet Akar, Merih Bırlık, Nurullah Akkoç, Ian C Chikanza, Fatoş Onen

    Türkiye parazitolojii dergisi / Türkiye Parazitoloji Derneği = Acta parasitologica Turcica / Turkish Society for Parasitology. 01/2010; 34(3):156-60.

    The aim of this study was to examine the serum levels of MIF and leptin in patients infected with Trichinella britovi. Thirtysix patients with acute trichinellosis and 20 healthy control subjects were included in the study. Serum high sensitive C-reactive protein (hs-CRP), MIF and leptin levels were... [more] The aim of this study was to examine the serum levels of MIF and leptin in patients infected with Trichinella britovi. Thirtysix patients with acute trichinellosis and 20 healthy control subjects were included in the study. Serum high sensitive C-reactive protein (hs-CRP), MIF and leptin levels were studied. Assessments were performed in the patients group during acute infection and after the treatment periods and we also compared these values with healthy controls. In the patients, hs-CRP, leukocyte and eosinophil counts, and the levels of muscle enzymes in the acute infectious period were found to be significantly higher than those in the post treatment period (p < 0.05). Both leptin and MIF were higher in acute trichinellosis patients when compared to controls. However, this was only significant for leptin. This study indicates that leptin and MIF levels are increased in the sera of patients with acute trichinellosis.
  • 1.54
    Impact points
    Effect of levothyroxine replacement therapy on paraoxonase-1 and carotid intima-media thickness in subclinical hypothyroidism.

    Levent Kebapcilar, Abdurrahman Comlekci, Pinar Tuncel, Ahmet Solak, Mustafa Secil, Omur Gencel, Mustafa Sahin, Ismail Sari, Sena Yesil

    Medical science monitor : international medical journal of experimental and clinical research. 01/2010; 16(1):CR41-7.

    Paraoxonase-1 (PON-1) may play an important role in atherosclerosis. Atherosclerosis is an inflammatory disease and C-reactive protein is a marker for inflammation. The aim of this study was to determine serum PON-1 activity and high-sensitivity C-reactive protein (hs-CRP) levels and assess carotid ... [more] Paraoxonase-1 (PON-1) may play an important role in atherosclerosis. Atherosclerosis is an inflammatory disease and C-reactive protein is a marker for inflammation. The aim of this study was to determine serum PON-1 activity and high-sensitivity C-reactive protein (hs-CRP) levels and assess carotid intima-media thickness, a marker of early atherosclerotic changes, in patients with subclinical hypothyroidism. hs-CRP concentrations and PON-1 activity with respect to carotid intima-media thickness were evaluated in 38 subclinical hypothyroidism patients (normolipidemic, mean age: 49.79+/-10.04 years) before and after 3 months of stable euthyroidism and compared with those of 19 euthyroid normolipidemic healthy individuals (mean age: 49.95+/-8.12 years). At baseline, the patients with subclinical hypothyroidism had similar levels of PON-1 activity and hs-CRP and a similar lipid profile as the controls; however, the carotid intima-media thickness was greater than in the controls. Levothyroxine treatment had no effect on serum PON-1 activity and hs-CRP level, but it resulted in a significant reduction in carotid intima-media thickness in the subclinical hypothyroidism patients. PON-1 activity and hs-CRP levels did not significantly differ between subclinical hypothyroid patients and controls. Although levothyroxine treatment might have the potential to reverse the progression of atherosclerosis in subclinical hypothyroid patients, PON-1 activity and hs-CRP levels were not affected by this treatment. The reduction in carotid intima-media thickness was independent of the decrease in serum lipid profile or other variables.
  • Increased prevalence of M694V in patients with ankylosing spondylitis: additional evidence for a link with familial mediterranean fever

    N. Akkoc, I. Sari, S. Akar, O. Binicier, M. G. Thomas, M. E. Weale, M. Birlik, Y. Savran, F. Onen, N. Bradman, C. A. Plaster

    Arthritis Rheum. 01/2010; 62(10):3059-63.

    OBJECTIVE: To assess whether there is a statistically significant difference in the frequency of common MEFV allele variants in patients with ankylosing spondylitis (AS) as compared with control patients with rheumatoid arthritis (RA) and with healthy control subjects. METHODS: Sixty-two patients wi... [more] OBJECTIVE: To assess whether there is a statistically significant difference in the frequency of common MEFV allele variants in patients with ankylosing spondylitis (AS) as compared with control patients with rheumatoid arthritis (RA) and with healthy control subjects. METHODS: Sixty-two patients with AS, 50 healthy control subjects, and 46 patients with RA were assessed for the presence of MEFV variants. Exon 10 was analyzed by direct sequencing. E148Q was analyzed by restriction endonuclease enzyme digestion (REED) or by direct sequencing when REED analysis failed. RESULTS: The allele frequency of all MEFV variants in the AS group was significantly higher than that in the pooled control group of healthy subjects plus RA patients (15.3% versus 6.8%; P = 0.021). M694V was the only variant that was significantly more common in the AS group than in the combined or individual control groups (P = 0.026 for AS patients versus healthy controls, P = 0.046 for AS patients versus RA patient controls, and P = 0.008 for AS patients versus healthy and RA patient control groups). The carriage rate of M694V was also significantly higher in the AS patient group than in the combined control group (odds ratio 7.0, P = 0.014). Neither M694V nor any other MEFV variant showed a correlation with most of the disease-related measures examined. CONCLUSION: We found an increased frequency of MEFV variants in AS patients as compared with healthy controls and with RA patient controls. This was primarily due to the presence of M694V. The roles of other exon 10 variants, as well as the relationship between the variant status and the severity and clinical course of the disease, need to be explored in further studies that include sufficiently large sample sizes.
  • 2.25
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