Evaluation of serum fibroblast growth factor-23 in patients with axial spondyloarthritis and its association with sclerostin, inflammation, and spinal damage.

The mechanisms underlying new bone formation in individuals with axial spondyloarthritis (axSpA) remain unclear; however, low levels of sclerostin (SOST) may be associated with development of syndesmophytes in those with ankylosing spondylitis (AS). Expression of fibroblast growth factor-23 (FGF-23), another osteocyte factor, is high in those with osteoporosis and chronic renal failure, but levels in those with axSpA are unknown. To evaluate serum FGF-23 and SOST levels in axSpA patients, and to assess their relationship with inflammation and structural damage. In total, 109 axSpA patients (55 with AS and 54 with non-radiographic axSpA) and 57 healthy control (HC) subjects were included in the analysis. Serum concentrations of FGF-23 and SOST were measured and correlation analysis was performed. The presence of syndesmophytes and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) were used to assess structural damage. Levels of serum FGF-23 in axSpA patients were significantly higher than those in HCs [median (interquartile range-IQR) FGF-23 level, pg/ml; AxSpA = 144 (82.3-253.2), HC = 107 (63.3-192.8), p = 0.010]; however, there was no difference in SOST levels. FGF-23 levels correlated with the erythrocyte sedimentation rate (ESR) (r = 0.265, p = 0.006) and serum C-reactive protein (CRP) level (r = 0.229, p = 0.010). In the axSpA, SOST levels correlated negatively with mSASSS (r = - 0.283, p = 0.007), whereas those in the AS group correlated negatively with CRP (r = - 0.426, p = 0.001). Serum FGF-23 levels were high in axSpA patients. Increased FGF-23 was associated with inflammation, but not with SOST levels or disease activity. SOST correlated negatively with both inflammation and structural damage.

Evaluation of periostin and factors associated with new bone formation in ankylosing spondylitis: Periostin may be associated with the Wnt pathway.

OBJECTIVE: Periostin has been shown to be involved in bone anabolism through the regulation of Wnt-ß-catenin signaling. It may be one of the pathogenic mechanisms in syndesmophyte formation in ankylosing spondylitis (AS). The aim of this study was to evaluate serum periostin levels in patients with AS and to assess relationships among biomarkers of bone formation and periostin in disease outcomes, particularly radiographic changes. METHODS: Ninety-seven consecutive AS patients (78% male) and 48 healthy controls (75% male) were included in the study. Serum periostin, dickkopf-1 (DKK-1), sclerostin and vascular endothelial growth factor (VEGF) levels were measured using commercially available enzyme-linked immunosorbent assay kits. Disease-related characteristics of patients were assessed using Ankylosing spondylitis disease activity score - C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index, Bath AS Functional Index and Bath AS metrology index. Radiographs were scored using the modified New York criteria and modified Stokes AS spinal score (mSASSS). RESULTS: Compared with control subjects, patients with AS had significantly lower serum levels of periostin (P < 0.001) and sclerostin (P < 0.001), but higher serum levels of VEGF (P < 0.001) and high-sensitivity CRP (P < 0.001). Serum periostin (P = 0.005) and sclerostin levels (P = 0.016) were significantly lower in patients with very high disease activity according to ASDAS-CRP. Current age (P = 0.009), age at symptom onset (P = 0.021) and hip joint involvement (P = 0.012) were independently associated with the development of syndesmophyte, in contrast to biomarkers of bone metabolism that we evaluated. CONCLUSION: Our results suggest that periostin is down-regulated in AS patients with highly active disease and may contribute to disease pathogenesis through an interaction with Wnt signaling.

Oxidative stress and related factors in patients with ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine and sacroiliac joints of unknown etiology. Recent studies have reported increased oxidative stress, which is implicated in the pathogenesis of a number of diseases, in AS. The purpose of this study was to investigate oxidative stress and related factors in AS. MATERIAL AND METHODS: Eighty-five patients with AS [36 (16-64) years; 65 male/20 female] and 56 healthy subjects [36 (21-63) years; 39 male/17 female] with no known cardiovascular risk factors were enrolled. Serum total oxidant status (TOS) and total anti-oxidant status (TAS) were studied. The Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis disease activity index (BASDAI), and Bath ankylosing spondylitis metrology index (BASMI) were calculated. A logistic regression model was used to identify the independent risk factors for TOS. RESULTS: No differences were observed in terms of demographic characteristics, laboratory findings, or TAS concentrations between the patient and control groups. However, the serum TOS levels were significantly higher in the AS group than in the controls (p=0.003). The comparison of cases of active (BASDAI ≥4) and inactive AS revealed significantly higher TOS levels in the active disease group. The TOS and TAS concentrations did not differ between patients treated with biological agents and those treated with conventional agents. Correlation analysis yielded significant correlations between TOS and TAS, BASMI, BASFI, BASDAI, erythrocyte sedimentation rate (ESR), and high-sensitive C-reactive protein (hs-CRP) (p<0.05; r values ranged from 0.291 to 0.452) and a positive correlation between TAS and BASMI (p<0.05; r=0.344). Based on regression analysis, BASDAI, BASMI, and hs-CRP independently predicted the TOS levels [p<0.05, R2: 0.262, and standard error of the estimate (SEE): 10.96]. CONCLUSION: Oxidative stress levels were higher in patients with AS than in healthy subjects. Patients with active disease status had significantly higher oxidative stress than patients with inactive disease status and healthy controls. Treatment status has no effect on TOS, and BASMI, BASDAI, and hs-CRP are independent variables associated with TOS. The TAS levels were found to be associated with only BASMI.

Biocompatibility of MG-63 cells on collagen, poly-L-lactic acid, hydroxyapatite scaffolds with different parameters.

PURPOSE: In this study, osteoblast-like MG-63 cells were cultured on 3 different scaffold types composed of (a) collagen + poly-L-lactic acid (PLLA), (b) collagen + hydroxyapatite (HA; 30ºC) or (c) collagen + hydroxyapatite (HA; 37ºC) and produced with different porosities. METHODS: Biomechanical properties of the scaffolds were characterized by tensile strength measurements. Properties of the cell-seeded scaffolds were evaluated with scanning electron microscopy (SEM). Cell adhesion and proliferation capacities were evaluated. Alkaline phosphatase (ALP) levels in media were measured. Transmission electron microscopy (TEM) and histological analyses were used to assess morphological characteristics. RESULTS: Our results showed that collagen-based PLLA and HA scaffolds have good cell biocompatibility. MTT test showed that the scaffolds exhibited no cytotoxicity. According to the force and displacement data, collagen + HA at 37ºC showed the highest mechanical strength and displacement. CONCLUSION: The results suggest that collagen-based PLLA and HA scaffolds might improve osteoblastic growth in vitro and have biomaterial integration potential in possible therapeutic approaches for future clinical studies.

Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study.

OBJECTIVES: New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. METHODS: Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. RESULTS: Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. CONCLUSION: Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis.

Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study

OBJECTIVES: New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. METHODS: Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. RESULTS: Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. CONCLUSION: Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis. .

Increased levels of macrophage migration inhibitory factor in patients with familial mediterranean Fever.

OBJECTIVE: To determine the level of macrophage migration inhibitory factor (MIF), its relationship with Mediterranean fever (MEFV) gene mutations and oxidative stress in familial Mediterranean fever (FMF). METHODS: Fifty one unrelated attack free FMF patients (24 M and 27 F, 32.8±8.7 years) and 30 healthy controls (16 M and 14 F, 32.7±7 years) were included in the study. Serum MIF, total oxidant status (TOS) and total anti-oxidant status (TAS) were studied. RESULTS: Age, sex distribution, anthropometrical indices, smoking status, serum lipids and TAS concentrations were similar between the patients and controls. However; erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MIF, and TOS were significantly higher in the patients' group compared with healthy subjects. MIF, TOS and TAS levels were not different between patients with or without M694V mutations. CONCLUSION: We found increased concentrations of MIF in patients with FMF. Increased MIF levels were significantly correlated with oxidative stress and in regression analysis MIF concentrations were independent from the inflammatory activity as assessed by ESR and CRP. M694V mutations seem no effect on MIF and oxidative stress.

Evaluation of circulating endothelial biomarkers in familial Mediterranean fever.

The aim of this was to evaluate some of the vascular biomarkers and cytokines related with atherosclerosis in regularly treated and attack-free familial Mediterranean fever (FMF) patients. Forty (21 males [M] and 19 females [F], 31 [15-58] years) FMF patients and eighteen healthy controls (11 M and 7 F, 35.5 [19-46] years) with no known cardiovascular (CV) risk factors were included. All patients were receiving regular colchicine treatment, and examinations were performed during attack-free periods. Serum samples were used for the determination of high-sensitive C-reactive protein (hs-CRP), tissue factor (TF), tissue plasminogen activator (t-PA), osteoprotegerin (OPG), interleukin-6 (IL-6), IL-17, and IL-23. Plasma samples were used for the determination of asymmetric dimethylarginine (ADMA) and thrombomodulin (TM). Age, sex distribution, waist circumference, body mass index, smoking status, and serum lipids were similar between the patients and controls (P > 0.05). The concentrations of (hs-CRP) and IL-17 were significantly higher in FMF patients compared with controls (P < 0.05). On the other hand, IL-6 and IL-23 levels were not different between the groups (P > 0.05). ADMA, OPG, and TM concentrations were significantly lower in the patients' group compared to those of controls (P < 0.05). However, vWF, TF, and t-PA levels were similar between the groups (P > 0.05). FMF patients receiving regular colchicine therapy during inactive disease state had significantly lower levels of vascular injury parameters.

Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis.

INTRODUCTION: The current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA. METHODS: This study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, disease extent index-Takayasu, physician's global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Unacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity. CONCLUSIONS: This study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity.

Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease of spine and sacroiliac joints; it is characterized by new bone formation, and the disease processes can be accompanied by osteoporosis. In the present study, we investigated changes in bone mineral density (BMD) and in the levels of various bone turnover-related biomarkers and cytokines in a cohort of AS patients, with regard to clinical parameters, disease activity, and treatment regimen. METHODS: 55 AS patients and 33 healthy controls included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and radiologic changes were scored by the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. Various biomarkers and cytokines of bone turnover including osteoprotegerin (OPG), serum band 5 tartrate-resistant acid phosphatase (TRAP-5), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), and sclerostin were studied. RESULTS: The levels of TRAP-5, NTX, sRANKL, sclerostin, sFRP-1, DKK-1, and IFNγ, were similar between the patients and controls (p > 0.05), while BMD of femoral neck, and OPG levels were significantly lower in AS patients (p < 0.05). In a subgroup analysis, patients with active disease had significantly higher concentrations of OPG compared with the inactive group. Rest of the biomarkers and cytokines of bone turnover were similar between the active and inactive disease groups. Subgroup analysis of patients receiving anti-TNFα agents and conventional therapy revealed that OPG concentrations were significantly lower in the patients receiving biological drugs, while BAP and DKK-1 were significantly higher in the patients treated with conventional agents. CONCLUSIONS: In this cross-sectional study we showed that OPG levels were significantly lower in AS patients compared to healthy subjects. On the other hand, the levels of wingless (Wnt) signal pathway inhibitors seem not altered. Ectopic bone formation in AS may be related to dysfunction of these molecules at the cellular level.

The effect of regular colchicine treatment on biomarkers related with vascular injury in newly diagnosed patients with familial Mediterranean fever.

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.

Evaluation of various endothelial biomarkers in ankylosing spondylitis.

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.

Down-regulation of adiponectin in patients with familial Mediterranean fever during attack-free period.

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.

Evaluation of the T helper 17 axis in ankylosing spondylitis.

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-ß, IL-17A, and IL-23 were measured in serum sample using commercially available ELISA kits. Cytokines including IL-6, IL-12, TGF-ß, 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.

Pathogenesis of rhinitis in rats with experimentally induced hypothyroidism.

BACKGROUND: Hypothyroidism is accepted as one of the hormonal factors leading to non-allergic rhinitis. Nasal obstruction and runny nose due to an increase in submucosal connective tissue and mucous gland hypertrophy are the prominent symptoms in hypothyroidism-induced rhinitis at humans. The aim of this study was to analyze the biochemical and histopathological changes in the nasal mucosa of the rats with thyroidectomy-induced hypothyroidism and to compare them with those of a control group. METHODS: A total of 60 adult male Wistar Albino rats were included in the study. The rats constituting the test and the control groups were randomly divided into 3 subgroups (T1-3 and C 1-3). While the rats in the test group underwent thyroidectomy, in the control group the incision was sutured without any interventions after exposure of thyroid tissues of the rats. The nasal and paranasal sinus regions of all the rats were carefully dissected and tissue samples were obtained for pathological examinations. RESULTS: In the rats in T1, T2, and T3, the decrease in serum glucuronic acid levels before and after thyroidectomy was statistically significant (p = 0.001, p = 0.003, and p = 0.002, respectively). The difference between the test and the control groups was statistically significant in terms of inflammation at the end of 12 weeks (p = 0.002). CONCLUSIONS: An increase in acid mucopolysaccharidase production due to TSH has been suggested to cause congestion in tissues. Although our study supports the data in the literature up to date, we consider that further clinical and experimental studies are necessary for this verification.

Fetuin-A and interleukin-18 levels in ankylosing spondylitis.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Fetuin-A and IL-18 levels seem to be increased in AS patients regardless of disease activity and treatment type.

Oral contraceptives alone and with spironolactone increase sCD40 ligand in PCOS patients.

BACKGROUND: The present study was designed to determine the effect of oral contraceptives (OCP) and OCP plus spironolactone (Sp) on plasma soluble CD40L levels in polycystic ovary syndrome (PCOS) patients. METHODS: Fifty-six women with PCOS were randomized into two treatment protocols: ethinylestradiol + cyproterone acetate (2 mg, EE/CA; n = 28), and EE/CA with spironolactone (Sp; n = 28). Plasma sCD40L levels were measured before and after a 3-month treatment. RESULTS: Before the initiation of treatment, the sCD40L levels were not significantly different between the groups [EE/CA (1.33 ng/mL) vs. EE/CA + Sp (1.23 ng/mL); P > 0.05]. In the post-treatment period, sCD40L concentrations were increased compared with pre-treatment values in the EE/CA and EE/CA + Sp groups (1.33 vs. 2.70 ng/mL, P = 0.011; and 1.23 vs. 2.41 ng/mL, P = 0.017; respectively). CONCLUSION: Increased plasma concentrations of sCD40L are associated with OCP and OCP + Sp treatment regimens in PCOS patients.

The influence of Helicobacter pylori eradication on leptin, soluble CD40 ligand, oxidative stress and body composition in patients with peptic ulcer disease.

OBJECTIVE: To determine the effect of Helicobacter pylori (H. pylori) eradication on blood levels of soluble CD40 ligand, leptin, oxidative stress and body composition in patients with dyspepsia infected with H. pylori. METHODS: The infection of H. pylori was based on the presence of both (14)C urea breath test (UBT) and histology. Patients were given triple eradication therapy for 14 days and at 3 months after the treatment, (14)C UBT was reinstituted. Fasting glucose, leptin, body composition, soluble CD40 ligand, total oxidant status (TOS) were studied before and at 3 months after the treatment. RESULTS: In 33 subjects, H. pylori infection was successfully eradicated. sCD40L, and TOS levels were significantly decreased after H. pylori eradication. The percentage of body fat and body fat mass significantly decreased whereas the fat free mass (FFM) increased after eradication. However, eradication of the organism yielded no differences in leptin levels. CONCLUSION: These findings suggest that H. pylori eradication reduces the sCD40L and oxidative stress, fat mass with a significant increase in fat free mass. Thus, eradication of H. pylori infection not only improves ulcer healing, but may also reduce the presumed atherosclerosis risk.

Increased levels of asymmetric dimethylarginine (ADMA) in patients with ankylosing spondylitis.

OBJECTIVE: Endothelial dysfunction is present in ankylosing spondylitis (AS). However, the etiology of events is still unclear. The aim of the present study was to investigate whether there are abnormalities in nitric oxide (NO) metabolism and endothelin-1 (ET-1) in AS patients. METHODS: Subjects without any classical cardiovascular (CV) risk factors were studied. Fasting glucose, serum lipids, high sensitive CRP (hsCRP), ESR, asymmetric dimethylarginine (ADMA) and ET-1 were studied. Patients were also evaluated with the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Disease Activity Index. RESULTS: A total of 48 AS patients (38.6+/-10.6 years; 36M/12F) and 38 controls (36.4+/-11.1 years; 27M/11F) were studied. Acute phase reactants including hsCRP, and ESR were significantly increased in the patients group (p<0.05). Serum ADMA concentrations were also significantly higher in AS than in controls. Plasma levels of ET-1 did not differ between the groups (p>0.05). Comparison of three groups (conventional and anti-TNF treatment groups and controls) revealed that ADMA was significantly higher in the conventional treated AS than in controls. The levels of ADMA were not different between anti-TNF group and healthy subjects. Plasma ET-1 concentrations were similar between groups (p>0.05). Correlation analysis yielded significant correlations between ADMA, hsCRP, LDL cholesterol, HDL cholesterol and triglycerides (p<0.05). CONCLUSION: The increased ADMA levels obtained in a group of relatively young AS patients who did not have classical CV risk factors suggest that NO metabolism is impaired in AS. On the other hand, anti-TNF treatments may have a beneficial effect on vascular function in AS.