Aynur Kirbas

soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD

Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition, and progresses with acute exacerbations. (AE). During AE, levels of acute phase reactants such as C-reactive protein (CRP) and inflammatory cells in the circulation increase. Soluble urokinase-type plasminogen activator receptor (suPAR) levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation. The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD) and response to treatment. Methods The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment. Results We found that fibrinogen (P<0.001), CRP (P<0.001), and suPAR (P<0.001) were significantly higher in patients with AE-COPD than in healthy controls. Fibrinogen (P<0.001), CRP (P=0.001), and suPAR (P<0.001) were significantly decreased by the seventh day of treatment. However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD. There was a correlation between fibrinogen, CRP, and suPAR. However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression. In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively). Serum suPAR was negatively correlated with forced expiratory volume in 1 second (r=−478, P=0.001). Conclusion suPAR is a marker of acute inflammation. It is well correlated with such inflammation markers as CRP and fibrinogen. suPAR can be used as a predictor of AE-COPD and in monitoring response to treatment.

Is resveratrol a potential substitute for leuprolide acetate in experimental endometriosis

OBJECTIVE Resveratrol, a phytoalexin polyphenol, has anti-angiogenic, antioxidant, anti-inflammatory properties. We aimed to compare the anti-inflammatory and anti-angiogenic effects of resveratrol and leuprolide acetate (LA) in an experimental endometriosis model. STUDY DESIGN A prospective experimental study was conducted in a University Surgical Research Center. Thirty-three non-pregnant female Sprague-Dawley rats, in which experimental model of endometriosis were surgically induced were randomly divided into four groups. Group 1 was administered 30 mg/kg resveratrol i.m. for 14 days, group 2 was given 1mg/kg s.c. single dose LA, group 3 was administered both resveratrol and LA, and group 4 had no medication. After two weeks medication rats were sacrificed and size, histopathology and immunreactivity to matrix metalloproteinase (mmp)2, mmp9, vascular endothelial growth factor (VEGF) of the endometriotic implants were evaluated. Plasma and peritoneal fluid levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were analyzed. RESULTS The endometriotic implant volumes, histopathological grade and immunreactivity to mmp2, mmp9 and VEGF were significantly reduced (p<0.001), and plasma and peritoneal fluid levels of IL-6, IL-8 and TNF-α were significantly decreased in group 1 and group 2 in comparison to group 3 and group 4 (p < 0.001). CONCLUSION Resveratrol alone is a potential agent for the treatment of endometriosis and may be an alternative to LA. In contrast, the combination of LA and resveratrol decreased the anti-inflammatory and anti-angiogenic effects of each agent. Since resveratrol is widely used as an alternative therapy for a variety of conditions, it can undermine the effectiveness of LA. Therefore, caution should be exercised when used in combination with other agents.

Paraoxonase and arylesterase activity and total oxidative/anti-oxidative status in patients with idiopathic Parkinson's disease.

This study investigated serum paraoxonase (PON1) and arylesterase activity along with determination of oxidative status via measurement of total oxidant status (TOS), total anti-oxidant status (TAS) and oxidative stress index (OSI) in patients with Parkinsons disease (PD) and compared results with data from healthy controls. A total of 82 subjects, including 42 patients with idiopathic PD, newly diagnosed and untreated (24 men, 18 women, aged 47-66 years) and 40 healthy controls were enrolled in this study. We aimed to evaluate the oxidative status of PD patients via measurement of serum TOS and TAS and estimation of OSI using new automated methods. PON1 and arylesterase activities were measured spectrophotometrically. Serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein (LDL) cholesterol and triglyceride levels were measured using routine methods. TAS levels of PD patients were significantly lower than that of controls (p<0.05). TOS levels of PD patients were higher than those of controls (p<0.05). PON1 and arylesterase activities of PD were lower than those of controls (p<0.05). Serum levels of total and LDL cholesterol were significantly reduced in PD patients. In conclusion, the presence of high TOS and OSI levels together with low levels of TAS in PD patients supports the important role of oxidative stress in the pathophysiology of PD. Since oxidative stress is involved in neurodegeneration, selecting anti-oxidants, metal chelators or other compounds boosting endogenous enzymatic and non-enzymatic defense mechanisms seems to be an obvious choice as treatment for PD.

Serum paraoxonase and arylesterase activity and oxidative status in patients with multiple sclerosis

The aim of this study was to investigate serum paraoxonase and arylesterase activities, and to determine oxidative status via the measurement of total oxidant status (TOS), total antioxidant status (TAS) and the oxidative stress index (OSI) in patients with relapsing-remitting multiple sclerosis (RRMS). Results were compared with data from healthy controls. A total of 60 subjects, including 30 newly diagnosed and untreated patients with RRMS (20 females, 10 males, 18-40 years of age) and 30 healthy controls (20 female, 10 male 20-40 years of age) were enrolled in this study. The oxidative status of the RRMS patients was measured by TOS, TAS and estimation of the OSI was made by a new automated method. Paraoxonase (PON1) and arylesterase activities were measured spectrophotometrically. TAS levels of RRMS patients were significantly lower than that of controls (p < 0.05). TOS levels of RRMS patients were higher than that of controls (p < 0.05). PON1 and arylesterase activities of RRMS patients were lower, but not significantly, than those of controls (p > 0.05). There was no correlation between serum PON1 activity and OSİ in patients with RRMS (p > 0.05). Hypercholesterolemia was not observed in multiple sclerosis patients. In conclusion, although the mechanism underlying the significant reduction of TAS levels of multiple sclerosis patients compared with those of controls is unknown, the results imply that endogenous antioxidants may have been exhausted by increased oxidative stress and we believe that additional antioxidant treatment might be beneficial for these patients.

Elevated serum osteoprotegerin levels predict in-hospital major adverse cardiac events in patients with ST elevation myocardial infarction

The aim of our study was to investigate whether osteoprotegerin (OPG) is related to in-hospital major adverse cardiac events (MACE) and reperfusion parameters in patients with ST elevation myocardial infarction (STEMI). The OPG/receptor activator of nuclear factor-κB (RANK)/RANK ligand pathway has recently been associated with atherosclerosis. OPG is a predictor of cardiovascular events in patients with acute coronary syndrome. This study included 96 consecutive patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Two groups with equal number of patients were formed according to median OPG level. The association of OPG levels on admission with post-procedural reperfusion parameters, and in-hospital MACE were investigated. Patients with higher OPG levels displayed higher neutrophil/lymphocyte ratio, admission troponin, admission glucose, and high-sensitive C-reactive protein. Higher OPG levels were associated with increased thrombolysis in myocardial infarction (TIMI) risk score, TIMI risk index, pain to balloon time, need for inotropic support, shock, and MACE, mainly driven by death. Reperfusion parameters were not different between the two groups. TIMI risk score, TIMI risk index, myocardial blush grade, estimated glomerular filtration rate (eGFR), number of obstructed vessels, and OPG significantly predicted adverse cardiac events. Multiple logistic regression analysis revealed OPG as an independent predictor of MACE as well as eGFR, number of obstructed vessels, and corrected TIMI frame count. OPG, a bidirectional molecule displaying both atheroprotective and pro-atherosclerotic properties, is currently known as a marker of inflammation and a predictor of cardiovascular mortality. The present study, for the first time, demonstrated that an increased OPG level is related to in-hospital adverse cardiovascular events after primary PCI in patients with STEMI.

Serum levels of homocysteine, asymmetric dimethylarginine and nitric oxide in patients with Parkinson's disease.

Objectives: Endothelial dysfunction has been implicated as a crucial event in the development of several neurodegenerative diseases. The aim of this study was to investigate the serum homocysteine, asymmetric dimethylarginine (ADMA) and nitric oxide (NO) levels in patients with Parkinson’s disease (PD) and to compare the results with data from healthy controls. Methods: A total of 132 subjects, including 82 idiopathic PD patients who were newly diagnosed and untreated (47 males, 35 females, mean age of 60.8 ± 7.1 years) and 50 healthy controls (28 males, 22 females, mean age of 60.2 ± 6.7 years) were enrolled in this study. The serum ADMA and NO levels were determined using enzyme-linked immunosorbent assay (ELISA), while the homocysteine levels were determined by chemiluminescent microparticle immunoassay. Results: The ADMA and NO levels of the PD patients were significantly higher than those of the healthy controls. The serum ADMA levels were 0.70 ± 0.15 μmol/L in the PD patients and 0.50 ± 0.12 μmol/L in the healthy controls (p < 0.001). The serum NO levels were 78.7 ± 10.3 μmol/L in the PD patients and 59.9 ± 9.5 μmol/L in the healthy controls (p < 0.001). In addition, the ADMA and NO levels were significantly correlated with the serum homocysteine levels in patients with PD (r = 0.874, p < 0.001, r = 0.803, p = 0.005, respectively). Conclusion: In our study, the high ADMA and NO levels of patients with PD indicate endothelial dysfunction, and this dysfunction may play a role in PD pathogenesis. Larger studies, including randomised clinical trials in humans and animal studies, are needed to validate our findings and help in developing a better understanding of the pathogenesis of PD.

Protective effect of infliximab on methotrexate-induced liver injury in rats: unexpected drug interaction.

AIMS Although methotrexate (mtx) is a widely used agent to treat cancer and inflammatory diseases, its hepatotoxic effect limits for clinical utility. We aimed to investigate whether infliximab (inf), an inhibitor of tumor necrosis factor-alpha (TNF-α) has a protective effect against mtx-induced hepatotoxicity. MATERIALS AND METHODS For mtx group, the animals received an intraperitoneal single dose injection of mtx at a dose of 20 mg/kg. For inf group, the animals received an intraperitoneal single dose injection of inf at a dose of 7 mg/kg. For mtx + inf group, the single dose of inf at a dose of 7 mg/kg was given 72 h prior to mtx injection. After 72 h, a single dose of mtx 20 mg/kg was given. All rats were sacrificed 5 days after mtx injection. RESULTS TNF-α and nitric oxide (NO) levels of mtx group was significantly higher than the control (P < 0.001), inf (P < 0.001) and mtx + inf (P < 0.001) groups. Total score of histological damage was higher in the mtx group when compared with the mtx + inf group. Arginase and carbamoyl phosphate synthetase 1 (CPS-1) of mtx group was suppressed in comparison with the control group and was markedly increased in mtx + inf group. CONCLUSION Inf may partially prevent mtx-induced hepatic damage in rats. However, the combined usage of mtx and inf increases arginase and CPS-1 enzyme activities and at the same time blocks TNF-α. This combination especially in cancer patients may lead to cancer cell invasion and metastasis.

Topiramate ameliorates abdominal aorta cross-clamping induced liver injury in rats.

Background and Aim: Ischemia/reperfusion (I/R) injury in the liver occurs after a prolonged period of ischemia followed by restoration of hepatic blood perfusion. During the surgery of abdominal aorta, I/R injury causes damage to lower extremities and many organs, especially liver. The antioxidant and tumor necrosis factor-alpha (TNF-α) suppression effects of topiramate (TPM) have been reported in several studies. We evaluated the potential protective effect of TPM on cellular damage in liver tissue during I/R injury. Materials and Methods: Thirty male Wistar albino rats were divided into three groups: Control, I/R, and I/R plus TPM (I/R + TPM) groups. Laparotomy without I/R injury was performed in the control group. After laparotomy, cross-ligation of infrarenal abdominal aorta was applied for 2 h in I/R groups that was followed by 2 h of reperfusion. TPM (100 mg/kg/day) was orally administrated to the animals in the I/R + TPM group for seven consecutive days before I/R procedure. Results: The I/R groups TNF-α and interleukin-6 (IL-6) levels were significantly higher than those of the control (P = 0.010; P = 0.002) and I/R + TPM groups (P = 0.010; P = 0.002, respectively). Asymmetric dimethyl arginine (ADMA) levels of I/R group were higher than the control (P = 0.015) and I/R + TPM groups. I/R caused serious histopathological damage to liver tissue; however, TPM led to very low histopathological changes. Conclusion: Our data demonstrated that TPM treatment prominently decreases the severity of liver I/R injury. TPM pretreatment may have preventive effects on liver injury via I/R during intra-abdominal surgery.

Evaluation of Peripapillary Retinal Nerve Fiber Layer Thickness in Patients With Vitamin B12 Deficiency Using Spectral Domain Optical Coherence Tomography

Purpose: To compare peripapillary retinal nerve fiber layer (RNFL) thicknesses measured by Cirrus HD optical coherence tomography (OCT) of patients with vitamin B12 deficiency with healthy controls and to evaluate the correlation between the peripapillary RNFL thickness and plasma vitamin B12 levels. Materials and Methods: Forty-five patients (19 male and 26 female) with a diagnosis of vitamin B12 deficiency (patient group) and 45 age- and sex- matched healthy subjects (control group) were consecutively enrolled in this study. Average, temporal, nasal, inferior, and superior quadrant peripapillary RNFL thicknesses of each subject were obtained using the Cirrus HD OCT. Disc area (DA) and rim area (RA), central subfield thickness (CST), cube volume (CV), and cube average thickness (CAT) were also measured. Results: Mean age of each group was 33.1 ± 6.5 years (range: 21–45 years). Mean plasma vitamin B12 level was 114.8 ± 34.0 pg/mL in the patient group and was 405.1 ± 20.0 pg/mL in the control group (p < 0.001). The patient and control groups were similar regarding axial length, plasma folate levels, DA, RA, CST, CV, CAT, and RNFL thicknesses in superior, nasal, and inferior quadrants. However, average RNFL and RNFL in temporal quadrant were significantly thinner in the patient group than in the control group (p = 0.013 and p < 0.001, respectively). In addition, temporal (r = 0.356, p = 0.001) and average (r = 0.212, p = 0.045) peripapillary RNFL thicknesses were correlated with plasma vitamin B12 levels. Conclusion: We have shown that, as in other non-glaucomatous optic neuropathies, temporal quadrant RNFL thickness was thinner in patients with vitamin B12 deficiency and it was correlated with plasma vitamin B12 levels. Further studies are warranted to clarify the clinical relevance of these findings and the effects of vitamin B12 replacement therapy.

The Role of Hypoxia at Primary Dysmenorrhea, Utilizing a Novel Hypoxia Marker—Scube1

STUDY OBJECTIVE To determine the SCUBE1 levels in adolescents with primary dysmenorrhea. DESIGN A prospective cross-sectional study. SETTING A university hospital outpatient clinic, Rize, Turkey. PARTICIPANTS A total of 40 adolescent girls, 15 on menses and 25 not on menses. INTERVENTIONS AND MAIN OUTCOME MEASURES Demographic features and menstrual history of the participants were assessed and blood samples were obtained for detecting the platelet volume, platelet counts, and SCUBE1 levels of the participants. RESULTS No difference was detected between the 2 groups in mean platelet volume, platelet count, and SCUBE1 levels. CONCLUSION Future trials are required to investigate the relation between SCUBE1 levels and primary dysmenorrhea.