Comparison of fetuin-A and transforming growth factor beta 1 levels in patients with spondyloarthropathies and rheumatoid arthritis.

AIM: We investigated the serum transforming growth factor beta 1 (TGFß1) and fetuin-A levels, and determined the relationships between these biomarkers and disease activity, mobility and radiologic progression in patients with spondyloarthropathy (SpA) and rheumatoid arthritis (RA). METHOD: The study included 55 patients with SpA and 38 patients with RA, together with 28 healthy subjects. In AS patients, we assessed disease activity using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), functional ability using the Bath Ankylosing Spondylitis Functional Index (BASFI), and mobility using the Bath Ankylosing Spondylitis Metrology Index (BASMI), radiologic progression using the Bath Ankylosing Spondylitis Radiology Index (BASRI). Serum fetuin-A and TGFß1 were determined using enzyme-linked immunosorbent assay (ELISA) equipment. RESULTS: Fetuin-A was significantly higher in the axial SpA and RA groups than in healthy subjects (P < 0.01). Serum TGFß1 and fetuin-A levels were similar in the peripheral SpA group and in healthy subjects. A significant positive correlation was found between the fetuin-A and TGFß1 levels in the axial SpA, peripheral SpA, and RA groups (r = 0.293, P = 0.009; r = 0.215, P = 0.04; r = 0.223, P = 0.05, respectively). Significant correlations were found between fetuin-A and the BASMI and BASRI values in the axial SpA patients (r = 0.444, P = 0.031; r = 0.486, P < 0.001, respectively). CONCLUSION: We conclude that Fetuin-A may be one of the steps that can be active in disease progression in axial SpA patients.

Endocan, TGF-beta, and ADMA as Risk Factors for Endothelial Dysfunction and Possible Vascular Disease in Patients with Subclinical Hypothyroidism.

PURPOSE: Although the relationship between atherosclerosis and overt hypothyroidism has been confirmed, it remains controversial in cases of subclinical hypothyroidism. Higher TSH and similar T4 suggest differences in set-points or differences due to diagnostic limitations regarding subclinical hypothyroidism. Endothelial dysfunction (ED) is a marker rather than a precursor of cardiovascular disease. Asymmetric dimethylarginine (ADMA) and endocan are known as novel markers of ED in various diseases. Transforming growth factor-beta (TGF-ß) has a protective role against autoimmune diseases such as thyroiditis. This study aimed to determine the relationships between serum ADMA, endocan, TGF-ß, and the high-sensitivity C-reactive protein (hs-CRP) levels, a proven indicator of ED, in patients with SH. METHODS: Thirty-five patients with SH and 21 age- and sex-matched euthyroid subjects were included in the study. The levels of TSH, FT4, lipid parameters, endocan, ADMA, TGF-ß, and hs-CRP were measured. RESULTS: No significant differences in age or sex were found between the patient and control groups (p=0.294 and 0.881, respectively). Mean TSH level was higher in the patient group (p=0.005), whereas mean fT4 level was similar in two groups (p=0.455). The average hs-CRP, endocan, TGF-ß l level in the patient group was higher than control group (p=0.001; P=0.012; P=0.025; P<0.01 respectively). A positive correlation was found between the endocan and ADMA levels (r=0.760, p=0.000). ADMA levels also were positively correlated with hs-CRP. Both the TSH and low-density lipoprotein cholesterol (LDL-C) levels were positively correlated with the hs-CRP level. CONCLUSIONS: Subclinical hypothyroidism is associated with increased levels of serum endocan, ADMA, and TGF-ß, which are new markers for ED. In particular, ADMA was correlated with both endocan and hs-CRP levels. These findings are suggestive for increased risk of ED and subsequent development of atherosclerosis in patients with SH.

A Controversial New Approach to Address Hematological Parameters in Hashimoto's Thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is a common autoimmune disorder. Genetic, environmental, and immunological factors all play a role in the pathogenesis of HT, but the effects of lymphocytes and platelets on the pathophysiology of HT are still unknown. In this study, we evaluated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in HT groups and HT subgroups with low cardiovascular risks. METHODS: This study included 92 patients with HT and 38 control subjects. Among the HT patients, three subgroups were formed according to thyroid function: overt (n = 12), subclinical (n = 38), and euthyroid (normally functioning thyroid; n = 42). RESULTS: Age and gender distributions were similar between the patient and control groups. Body mass index was higher in the patient group than in the control group. The C reactive protein level was higher in patients than controls (p = 0.064). The thyroid stimulating hormone (TSH) level was higher and the mean free thyroxine level lower in the patient group than in the control group (p < 0.05). There were no differences between the groups with regard to leukocytes, neutrophils, platelets, or MPV (p > 0.05). The NLR and PLR were significantly different in one subgroup of HT patients relative to healthy subjects (p < 0.05). However, we did not find any statistical differences in the MPV among the three subgroups (p = 0.547). A positive correlation was found among the NLR, anti-thyroglobulin (TG) antibodies, and anti-thyroid peroxidase (TPO) antibodies (p < 0.01), although there was a negative correlation between the PLR, TSH, anti-TPO, and anti-TG (p < 0.001). CONCLUSIONS: A single marker or panel of biomarkers is not a consistent indicator of HT, but NLR combined with PLR testing may offer a more reliable diagnosis.

A New Explanation of Inflammation in Rheumatoid Arthritis Patients With Respect to Claudin-5, Matrix Metalloproteinase-9, and Neuroserpin.

OBJECTIVES: This study aims to investigate the relationship between neuroserpin (NSP) and claudin-5, as well as matrix metalloproteinase-9 (MMP-9), with respect to clinical activity of disease in patients with rheumatoid arthritis. PATIENTS AND METHODS: The study included a total of 75 patients (18 males, 57 females; mean age 48.12±11.23 years; range 20 to 60 years) who were admitted to the rheumatology outpatient facility at the Medical Faculty Hospital, Sakarya University, in October 2014. Patients were divided into four groups based on their Disease Activity Score 28 (DAS28) scores as remission group (n=16, DAS28 <2.6), low disease activity group (n=16, DAS28 between 2.6-3.2), moderate disease activity group (n=28, DAS28 between 3.2-5.1), and high disease activity group (n=15, DAS28 >5.1). Ten healthy subjects (HS) served as controls. RESULTS: Claudin-5, MMP-9, and NSP levels were significantly different in rheumatoid arthritis patients compared to HS (p=0.035, 0.026, and 0.014, respectively). Additionally, there were no differences between claudin-5 levels and disease activity among all RA groups. However, compared to HS, patient groups showed a significant difference (p=0.035) in terms of claudin-5 levels. Serum levels of MMP-9 were significantly different in moderate disease activity group compared to HS (p=0.013). Levels of NSP were significantly different in moderate disease activity and high disease activity groups compared to HS (p=0.008 and 0.031, respectively). CONCLUSION: Our study demonstrated the differential associations of endothelial function/dysfunction biomarkers and disease activity in rheumatoid arthritis. How and why this impairment occurs is not fully understood and more data regarding NSP, MMP, and claudin expression in plasma are warranted.

Overlooked hematological markers of disease activity in rheumatoid arthritis.

AIM: The aim of this study was to investigate the relationship between hematological markers and disease activity in patients with rheumatoid arthritis (RA). METHOD: The study was designed and performed in the Department of Rheumatology of the Sakarya University Faculty of Medicine. In total, 102 patients with RA were retrospectively enrolled. We used the Disease Activity Score of 28 joints (DAS28) instrument to evaluate disease activity. Laboratory assessments included complete blood cell counts, measurement of erythrocyte sedimentation rate (ESR) and assessment of C-reactive protein (CRP) level. Exclusion criteria included active infection and/or the presence of any hematological, cardiovascular or metabolic disorder. RESULTS: We found that the neutrophil lymphocyte ratio (NLR) and mean platelet volume (MPV) varied by disease activity status. NLR values correlated positively with the DAS28 scores of RA patients. Especially, higher NLR values (3.92 ± 0.31) were evident in the group exhibiting high-level disease activity, whereas the MPV values were lowest (7.11 ± 0.91 fL) in this group. Additionally, no significant difference was evident between DAS28 scores and platelet distribution width (PDW) values in patients with RA (r = -0.055, P = 0.124). CONCLUSIONS: We found that the MPV value may serve as a marker of the absence of acute-phase disease, and the NLR level as a marker of the presence of such disease, in patients with RA. More detailed analysis of disease activity is required to further explain the associations of the markers described above with disease activity.

Roles of claudin-5 and von Willebrand factor in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that affects approximately 1% of the world's population. The pathogenesis of RA is not understood fully. It is assumed that endothelial function is associated with the proinflammatory state of RA. Endothelial dysfunction/activation reflects the increased level of von Willebrand factor (vWF) and a shift toward prothrombotic activity of the endothelium. The present study was performed to investigate the possible relationships between vWF and claudin-5 and the level of disease activity in patients with RA. The study population was divided into four groups according to the disease activity score in 28 joints (DAS28): remission group (RG), 18 patients (DAS28 < 2.6); low disease activity group (LDAG), 23 patients (DAS28 > 2.6-3.2); moderate disease activity (MDAG), 23 patients (DAS28 > 3.2-5.1); high disease activity group (HDAG), 14 patients (DAS28 > 5.1); and control group (CG), 10 healthy subjects. Claudin-5 and vWF assessment were derived from serum samples gathered from the patients known to have RF and anti-CCP titers in the normal ranges. A high positive association of claudin-5 and vWF with the MDAG was observed (P < 0.001). The results of our study indicated that the relationship between vWF and claudin-5, which are indicators of endothelial cell dysfunction and tight junction activity, may be a predictor of disease activity. Further studies are required to investigate these pathways to shed light on the roles of claudin-5 and vWF in the progression of inflammation and other vascular conditions.

The Circulating Levels of Selenium, Zinc, Midkine, Some Inflammatory Cytokines, and Angiogenic Factors in Mitral Chordae Tendineae Rupture.

Chordae tendineae rupture process is associated with increased production of inflammatory and angiogenesis mediators in connective tissues, which contributes to chronic inflammation and pathogenesis of degenerative chordae. A few trace elements are known to possess antioxidant, anti-inflammatory, and antiangiogenic properties. Therefore, the aim of this study was to determine whether zinc, selenium, midkine (MK), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-BB (PDGF-BB), and reduced glutathione (GSH) levels are associated with inflammation and angiogenesis processes in the context of a potential etiology causing aggravation of mitral regurgitation and/or ruptured chordae tendineae. Seventy-one subjects comprising 34 patients with mitral chordae tendineae rupture (MCTR) and 37 healthy controls diagnosed on the basis of their clinical profile and transthoracic echocardiography were included in this study. The levels of GSH, MK, selenium, and zinc were found to be lower in the patients group when compared to control group. There were no significant difference in plasma TNF-α, IL-1ß, IL-6, IL-8, VEGF-A, and PDGF-BB levels between two groups. There were positive significant correlations between MK and GSH, MK, and selenium levels in patients with MCTR. According to our data in which selenium, zinc, MK, and GSH decreased in MCTR patients, inflammatory response, oxidative stress, and trace element levels may contribute to etiopathogenesis of mitral regurgitation and/or ruptured chordae tendineae.

Comparative proteomic approach in rat model of absence epilepsy.

The aim of this study was to investigate cellular proteins in the pathogenesis of the genetic rat model of absence epilepsy. Protein spots were identified with peptide mass fingerprinting analysis using matrix-assisted laser desorption ionization time of flight mass spectrometry. Data were gathered from the frontoparietal cortex and thalamus of Wistar Albino Glaxo/Rij (WAG/Rij) and Wistar by using two-dimensional gel electrophoresis (2D-PAGE). Six proteins (Clathrin light chain-A protein, Transmembrane EMP24 Domain-Containing Protein, Stathmin-4, Myosin Light Chain4, Rheb, phosphoserine phosphatase) were found to be differentially expressed in the frontoparietal cortex of WAG/Rij and Wistar rats in both age groups. Another set of six proteins (Protein FAM89A and Oasl1, Gemin2, NuDEL1, Pur-beta, 3-alpha HSD) were found to be differentially expressed in the thalamus of WAG/Rij and Wistar rats. Findings from the frontoparietal cortex suggest the presence of altered serine metabolism and increased vesicular trafficking in the frontoparietal cortex of WAG/Rij rats compared with Wistar rats. These differences in the protein levels might reflect the crucial role of these proteins and related pathways in the generation of absence seizures. In the thalamic specimens, age-dependent changes in protein expression were remarkable, suggesting that this phenomenon may be a precursor or a consequence of absence seizures. Our findings further highlight the potential role of the mTOR signaling pathway in absence epilepsy.

Effects of linoleic acid on generalized convulsive and nonconvulsive epileptic seizures.

BACKGROUND/AIM: To comparatively investigate the effects of linoleic acid on convulsive and nonconvulsive epileptic seizures. MATERIALS AND METHODS: Rats were divided into 3 groups: convulsive epileptic rats receiving only pentylentetrazole (PTZ) injections (group 1), convulsive epileptic rats receiving PTZ and linoleic acid (group 2), and Wistar Albino Glaxo rats from Rijswijk with genetic absence epilepsy receiving linoleic acid (group 3). The duration and severity of convulsive activity were determined in groups in which convulsive seizures were induced by PTZ. In group 3, intravenous linoleic acid was administered after 1-h baseline electroencephalography (EEG) recordings. The EEG recordings were analyzed. RESULTS: When groups 1 and 2 were compared, the delay in onset of minor seizures and the decrease in the number of rats developing major seizures were found statistically significant. When the mean spike-wave discharge number and duration values for the rats in group 3 were compared to baseline values, a statistically significant increase was found in the 1st and 6th hours and there was no significant difference in the 24th hour. CONCLUSION: While our study shows that linoleic acid may be effective in the treatment of generalized convulsive epilepsy along with conventional antiepileptic drugs used in epilepsy treatment, it reports that linoleic acid is not appropriate in the treatment of nonconvulsive epilepsies.

The effects of vagal nerve stimulation in focal cerebral ischemia and reperfusion model.

AIM: This study aimed to investigate the effects of VNS in transient middle cerebral artery occlusion and reperfusion (MCAO/R) rat model of ischemia based on behavioral, morphological, and molecular approaches. MATERIAL AND METHODS: Wistar albino rats were divided into 3 groups: ischemia-reperfusion (I/R), I/R+VNS, and sham (for I/R). Each group was further divided into two subgroups for the assessment of neurological deficits and infarct area, or biochemical parameters related to oxidative stress. RESULTS: The infarct area and neurological scores were significantly lower in I/R+VNS group compared with the I/R group. MDA levels were significantly higher in I/R group compared to control and I/R+VNS groups in the cortical and subcortical specimens. There were also betweengroup differences in terms of GSH levels. GSH levels were higher in sham group compared with and I/R and I/R+VNS groups in cortical specimens whereas these levels for lower in I/R group compared to control and I/R+VNS groups in the subcortical specimens. SOD activity was higher in control group compared to I/R and I/R+VNS groups both in the cortical and subcortical specimens. There was no difference between I/R and I/R+VNS groups in neither cortical nor subcortical specimens. CONCLUSION: The neuroprotective and antioxidant properties of VNS suggest its efficacy as a potential anti-ischemic treatment.