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Öğe Adrenomedullin and nitrite levels in children with minimal change nephrotic syndrome(Springer-Verlag, 2000) Balat, A; Çekmen, M; Yürekli, M; Gülcan, H; Kutlu, O; Türköz, Y; Yologlu, SNitric oxide (NO) serves many functions within the kidney, and recent evidence suggests that NO contributes to glomerular injury. Adrenomedullin (AM) is a novel hypotensive peptide originally isolated from human pheochromocytoma. Recent studies showed that plasma AM concentrations correlated with the extent of proteinuria. We have examined the possible role of these two agents by studying plasma and urinary total nitrite (NO-(2) + NO-(3)) and AM levels in children with minimal change nephrotic syndrome (MCNS). In comparison with healthy controls, children with MCNS had increased urinary nitrite excretion (mu mol/mg urinary creatinine), irrespective of whether the disease was in relapse or remission (3.2+/-0.2 in relapse, n=13; 1.9+/-0.3 in remission, n=12; 1.0+/-0.2 in controls, n=10, P<0.05). Plasma nitrite levels (mol/l) were high in relapse compared with controls (53.2+/-8.7 vs 32+/-4.0, P<0.05). Plasma AM levels (pmol/ml) were decreased in relapse (27.6+/-1.4 in relapse, 43.3+/-1.2 in remission, 41.5+/-1.6 in controls, P<0.05). Urinary AM levels (pmol/mg urinary creatinine) were significantly higher in relapse than in remission and in controls (156+/-43 in relapse, 56+/-18 in remission, 36+/-16 in controls, P<0.05). Our data indicate that NO may play a role in mediating the clinical manifestations of MCNS in children. However, changes in AM levels may be the result of heavy proteinuria.Öğe Altered diurnal variation of nitric oxide production in patients with panic disorder(Tohoku Univ Medical Press, 2004) Kaya, B; Ünal, S; Karabulut, AB; Türköz, YThe aim of this prospective study was to investigate the diurnal change in serum nitric oxide (NO) levels in active and remission phases of patients with panic disorder. This study included 15 patients fulfilling the criteria for panic disorder of Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition and 15 healthy controls matched for age and sex. All patients were receiving a selective serotonin reuptake inhibitor at therapeutic doses. The serum nitrite and nitrate levels of subjects were determined at 10: 00 a.m. after overnight fasting and at 3: 00 p.m. 2 hours after lunch. NO levels of all patients measured in the morning were significantly higher than those of controls. The patients were also divided into active and remission groups according to clinical status and Panic Agoraphobia Scale's cut-off point. There were no statistically significant differences in serum nitrite and nitrate levels of the active group between the 10:00 a.m. and 3:00 p.m. measurements. In contrast, statistically significant differences were found in the serum levels of nitrite (p<0.05) and nitrate (p<0.05) in the remission group. Notably, the afternoon nitrite and nitrate levels of the remission group were higher than those of the morning levels as seen in control subjects. Thus, diurnal variation of NO production is altered in patients with panic disorder but is resumed in the remission phase. The present study suggests that serum NO levels are a good marker for evaluation of panic disorder. (C) 2004 Tohoku University Medical Press.Öğe Comparison of serum NO, TNF-?, IL-1?, sIL-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus(Nature Publishing Group, 2002) Doganay, S; Evereklioglu, C; Er, H; Türköz, Y; Sevinç, A; Mehmet, N; Savli, HBackground Vitreal interleukin (IL)-1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels have previously been determined in patients with proliferative diabetic retinopathy (PDR). However, at present there is no cohort study linking serum levels of NO and many inflammatory cytokines such as TNF-alpha, IL-1beta, soluble IL-2 receptor (sIL-2R), IL-6 and IL-8 to the grade of the microvascular complications. Purpose To determine the relation between the stages of DR and the levels of serum NO, TNF-alpha, IL-1beta, sIL-2R, IL-6 and chemokine IL-8 in patients with diabetes compared with healthy controls. Methods Fifty-three consecutive patients with diabetes (25 men, 28 women) with or without DR and 15 non-diabetic healthy subjects (seven men, eight women) as controls were included in this prospective study. As an indicator for NO, serum total nitrite (NO2- + NO3-) levels (end-product of NO) were measured by the Griess reaction. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometric technique using an Immulite chemiluminescent immunometric assay. The patients with diabetes were classified into three groups according to the stage of DR: no DR (NDR; n = 16), non-proliferative DR (NPDR; n = 18) and PDR (n = 19). The data were analysed using a Mann-Whitney U-test and the results were expressed as mean +/- SE (range). Results The levels of IL-1beta and IL-6 were below the detection limits of the assay (for each, <5.0 pg/ml) in all patients with diabetes and controls. Soluble IL-2R levels ranged from 260 to 958 U/ml, with the highest values observed in the patients with PDR. In 47 of the 53 samples (89%) tested for diabetic patients, IL-8 levels were above the detection limits of the assay (5.0 pg/ml). IL-8 levels ranged from <5.0 to 25.0 pg/ml, with the highest mean values observed in PDR patients. TNF-alpha was detectable in 46 of 53 patients with diabetes (87%), ranging from <4.0 to 26.4 pg/ml, with again the highest values obtained in the patients with PDR. Serum NO levels ranged from 80 to 188 mumol/l, with the highest values obtained in patients with PDR. Taken together, the mean serum NO, sIL-2R, IL-8 and TNF-alpha levels increased with the stage of DR and the highest levels were found in patients with PDR. The PDR patients had significantly (for each, P < 0.001) higher serum NO (166.8 +/- 3.2 mumol/l), sIL-2R (807.9 +/- 33.3 U/ml), IL-8 (17.9 +/- 0.4 pg/ml) ;and TNF-alpha (15.0 +/- 0.8 pg/ml) levels compared with NPDR patients (149.5 +/- 2.1, 659.4 +/- 23.4, 12.9 +/- 1.1, 11.5 +/- 0.6, respectively), NDR patients (115.9 +/- 5.8, 373.8 +/- 15.0, 8.3 +/- 1.0, 6.6 +/- 0.9, respectively) and controls (116.6 +/- 2.3, 392.4 +/- 16.6, 7.2 +/- 0.3, 7.3 +/- 0.3, respectively). Serum levels of these parameters for NPDR patients were also significantly (for each, P < 0.01) higher compared with those of NDR patients and controls. On the other hand, serum NO, sIL-2R, IL-8 and TNF-alpha levels of patients with NDR were comparable with those of controls (for each, P > 0.05). Conclusion The results of the present study suggest that NO, sIL-2R, IL-8 and TNF-alpha may play important roles in the pathophysiology and progression of DR. We think that these potentially inflammatory cytokines and NO with their endothelial implications may act together during the course and progression of DR. These molecules may serve as therapeutic targets for the treatment and/or prevention of diabetes with its systemic and ocular microvascular complications.Öğe Degradation of vincristine by myeloperoxidase and hypochlorous acid in children with acute lymphoblastic leukemia(Pergamon-Elsevier Science Ltd, 2003) Özgen, O; Türköz, Y; Stout, M; Özugurlu, F; Pelik, F; Bulut, Y; Aslan, MVincristine (VCR) is an effective drug against acute lymphoblastic leukemia (ALL), many solid tumors, but not acute myeloid leukemia. It has been hypothesized that resistance of myeloblasts to VCR is related to myeloperoxidase (MPO) and production of hypochlorous acid (HOCl). We investigated the relationship between VCR degradation and MPO expression and serum HOCl concentrations in pediatric patients with ALL, lymphoma and solid tumors. We studied the sera from 43 children, of which 23 were newly diagnosed and as yet untreated cancer patients, 10 on chemotherapy and 10 healthy control subjects. Patients' sera were incubated with VCR alone or in the presence of taurine (T) or acetaminophen (APAP) and post-incubation VCR and HOCL concentrations were measured. Significant correlations between serum MPO expression, HOCl concentrations and VCR degradation were seen. In the chemotherapy group, MPO-positive patients produced high levels of HOCl and reciprocally low post-incubation VCR levels. HOCl and VCR concentrations in this group were significantly different than other groups studied. Both APAP and T inhibited VCR degradation in the sera of the chemotherapy group but not to the same degree. The effects seen here were consistent for both ALL and the lymphoma/solid tumor cases. Our results indicate that HOCl can increase VCR degradation in vitro in the serum and this effect is significantly more pronounced in pediatric patients undergoing chemotherapy. (C) 2003 Elsevier Science Ltd. All rights reserved.Öğe Effect of caffeic acid phenethyl ester on cartilage in experimental osteoarthritis(Springer-Verlag, 2002) Elmali, N; Avan, I; Türköz, Y; Mizrak, B; Germen, B; Bora, AActivation of nuclear factor kappa B (NF-kappaB) in synovial cells is seen in RA and OA patients. Caffeic acid phenethyl ester (CAPE) is a specific and potent inhibitor of NF-kappaB. We aimed to determine the in vivo effects of intra-articular injections of CAPE on cartilage in an experimental rabbit osteoarthritis (OA) model. Two groups of six New Zealand white rabbits underwent unilateral anterior cruciate ligament transection (ACLT). Four weeks after ACLT, the test group was injected with 150 mug/kg CAPE in 0.5% ethanol once daily for 2 weeks and the control group was injected the same amount of 0.5% ethanol intra-articularly. All rabbits were killed 2 weeks after the last injection, and cartilage tissue was evaluated morphologically. A histological score totaling 7 points was determined for each knee. The CAPE group showed significantly decreased cartilage destruction and reduced loss of matrix proteoglycans. The histological score for cartilage tissue was significantly better in the CAPE group than in the control group (3.0 +/- 0.25 vs 5.3 +/- 0.55, P=0.005). This study suggests that intraarticular injection of CAPE may protect cartilage against the development of experimentally induced OA.Öğe Investigation on serum Ca and P levels in cows with retained placenta(Scientific Technical Research Council Turkey, 1999) Öcal, H; Türköz, Y; Çetin, H; Kaygusuzoglu, E; Risvanli, A; Kalkan, CThis study was carried out to investigate serum Ca and P levels in 31 cows with retained placenta (RP) and 8 cows without RP (control group). The RP was observed following normal parturition in 21 cows (RPP), and the remaining 10 cows had RP after abortion (RPA). Serum Ca and P levels did not differ significantly between the cows with RP and the control group (p>0.05). When the cows with RP were subdivided into two groups as the cows with RPP and those with RPA; the difference in the levels of P between these groups and the control group was not significant (p>0.05). However, the average Ca level of the cows with RPP was significantly lower than that of the cows with RPA and the control group (p<0.05). There was an association between the sex of calf and serum Ca level in the cows with RP. The Ca level of the cows which had female carves was significantly lower than that of cows which had male calves (p<0.05). When the seasonal distribution of RP was considered, there was no significant difference between seasons in terms of Ca levels (p>0.05), whereas P levels of cows with RP (n=6) occured in spring were significantly lower than those of cows with RP (n=15) occured in summer (p<0.01).Öğe Potential salvage therapy for accidental intrathecal vincristine administration(Karger, 2000) Özgen, Ü; Soylu, H; Önal, SÇ; Mizrak, B; Türköz, Y; Kutlu, NO; Koçak, ABackground: Accidental intrathecal vincristine (VCR) administration results in severe neurotoxicity, usually fatal in outcome. No specific therapy for initrathecal VCR toxicity has been reported so far. In our recent report, complete in vitro degradation of VCR by hypochlorous acid (HOCl) was demonstrated. Methods: In this comparative study, we examined the in vivo effectivity of HOCl in the cerebrospinal fluid of 24 New Zealand rabbits following intracisternal VCR administration. Results: There were no significant clinical or histopathologic abnormalities in the control and HOCl groups; however, multiple necrotic foci on histopathological examination of brain sections in the VCR group were determined. There were significantly lower numbers of necrotic foci in brain sections of rabbits which received HOCl administration than those without therapy. Conclusion: Our results indicate that HOCl may reduce VCR neurotoxicity. Copyright (C) 2000 S. Karger AG, Basel.Öğe Serum homocysteine level is increased and correlated with endothelin-1 and nitric oxide in Behcet's disease(Bmj Publishing Group, 2002) Er, H; Evereklioglu, C; Cumurcu, T; Türköz, Y; Özerol, E; Sahin, K; Doganay, SBackground/aims: Beligei's disease (BD) is a systemic inflammatory vasculitis of young adults with unknown aetiology, characterised by endothelial dysfunction and occlusion in both deep venous and retinal circulation. Ocular involvement occurs in 70% of cases and is characterised by periphlebitis, periarteritis, vascular occlusion, and thrombosis leading to blindness despite vigorous treatment. Endothelin-1 (ET-1) is a vasoconstricting peptide while nitric oxide (NO) is a relaxing molecule and both are released by endothelium for blood flow regulation. Homocysteinaemia is a newly defined term connected to the increased risk of atherothrombotic and atherosclerotic systemic and retinal vascular occlusive diseases, and its role in the course of BID has not been previously described. The authors aimed to detect serum total homocysteine (tHcy), ET-1, and NO in BID and to assess if tHcy, ET-1, and NO are associated with ocular BD or disease activity. Methods: 43 consecutive patients with ocular (n = 27) or non-ocular (n = 16) BD (36.95 (SD 9.80) years, 22 male, 21 female) satisfying international criteria, and 25 age and sex matched healthy control subjects (37.88 (8.73) years, 13 male, 12 female) without a history of systemic or retinal venous thrombosis were included in this study. Patients were examined by two ophthalmologists with an interest in BID. Serum tHcy, ET-1, and NO concentrations were measured in both groups. Hype rhomocysteinaemia was defined as a tHcy level above the 95th percentile in the control group. Patients were divided into active and inactive period by acute phase reactants including (X, antitrypsin, alpha(2), macroglobulin, erythrocyte sedimentation rate, and neutrophil count. Results: The overall mean serum tHcy, ET-1, and NO levels were significantly higher in patients with BD than in control subjects (tHcy = 15,83 (4.44) v7.96 (2.66) ng/ml, p <0.001; ET-1 = 17.47 (4.33) v 5.74 (2.34) mumol/ml, p <0.001; NO = 37.60 (10.31) v 27.08 (7.76) mumol/l, p <0.00 1). Serum I tHcy, ET-1, and NO levels were significantly higher in active patients than in inactive patients and control subjects. In addition, among patients with ocular BID, the mean tHcy levels were significantly increased and correlated with ET-1 and NO levels when compared with non-ocular disease and control subjects. All acute phase reactant levels were significantly higher in active period than in inactive stage and controls. Conclusions: Elevated tHcy may be responsible for the endothelial damage in BD and may be an additional risk Factor for the development of retinal vascular occlusive disease, contributing to the poor visual outcome in these patients. Assessment of tHcy may be important in the investigation and management of patients with BD, especially with ocular disease.Öğe Serum levels of TNF-?, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behcet's disease(Carfax Publishing, 2002) Evereklioglu, C; Er, H; Türköz, Y; Çekmen, MAIM Behcet's disease (BD) is a systemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress. Methods: A total of 37 patients (19 men, 18 women) with BD (active, n = 17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometer technique using the immulite chemiluminescent immunometric assay. Lipid peroxidation was evaluated by Wasowicz et al. The levels of cytokines and lipid peroxidation in the active period were compared with the inactive period of the disease. Results are expressed as mean +/- standard error. Results: IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all samples. Mean levels of MDA (8.1 +/- 0.7 ?mol/l), sIL-2R (800 +/- 38 U/ml), IL-6 (12.6 +/- 1.1 pg/ml), IL-8 (7.2 +/- 0.4 pg/ml), and TNF-? (7.9 +/- 0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3 +/- 0.5 ?mol/l, p < 0.01; 447 +/- 16 U/ml, p < 0.001; 8.3 +/- 0.6 pg/ml, p = 0.006; 5.3 +/- 0.1 pg/mL p < 0.001; and 5.1 +/- 0.2 pg/ml, p < 0.001; respectively) or control subjects (2.1 +/- 0.2 ?mol/l, p < 0.001; 446 +/- 20 U/ml, p < 0.001; 6.4 +/- 0.2 pg/ml, p < 0.001; 5.4 +/- 0.1 pg/ml, p < 0.001; and 4.7 +/- 0.1 pg/ml, p < 0.001, respectively). On the contrary, only the mean IL-6 level was significantly different between inactive BD and control subjects (p = 0.02). All acute phase reactants were significantly higher in active BD than in inactive period (for each,p < 0.01). Conclusions: High levels of sIL-2R, IL-6, IL-8 and TNF-? indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-? seem to be related to disease activity. Increased lipid peroxidation suggests oxidative stress in BD and therefore tissue damage in such patients. Amelioration of clinical manifestations would be envisaged by targeting these cytokines, chemokines and lipid peroxidation with pharmacological agents.Öğe Use of pleural fluid C-reactive protein in diagnosis of pleural effusions(W B Saunders Co Ltd, 2000) Turay, ÜY; Yildirim, Z; Türköz, Y; Biber, Ç; Erdogan, Y; Keyf, AI; Ugurman, FThe aims of the study were to assess whether C-reactive protein (CRP) is a sensitive marker for discriminating between transudative and exudative and pleural effusions to evaluate whether it can be used to distinguish inflammatory pleural effusions from other types of effusion. Pleural fluid and serum CRP levels were obtained in 97 patients with pleural effusion, using an immunoturbidimetric method (Olympus AU-600 autoanalyser). We compared CRP levels between transudates and exudates, inflammatory effusions and other types of effusion. According to the criteria used, 16 patients were included in the transudate group and 81 patients in the exudate group. Pleural fluid CRP levels were significantly lower in the transudate group (P < 0.04; 14.9 +/- 4.9 mg l(-1) and 35.5 +/- 4.9 mg l(-1) respectively). Also, the ratio of pleural fluid to serum was significantly lower in the transudate group (P < 0.009 0.8 +/- 0.5 mg l(-1) and 2.8 +/- 0.7 mg l(-1), respectively). In the exudate group, 35 patients had neoplastic effusions, 10 chronic non-specific pleurisy, 19 tuberculous pleurisy, 16 parapneumonic effusion and one Dressier Syndrome. When these sub-groups were compared, the parapneumonic effusion subgroup CRP levels (mean 89 +/- 16.3 mg l(-1)) were significantly higher than those in the other subgroups, other exudate of neoplastic effusion. tuberculous pleurisy and chronic non-specific effusion and the transudate group (P < 0.0001; P < 0.0001; P < 0.0004 and P < 0.0001. respectively). The ratio between pleural fluid and serum CRP was significantly higher in the parapneumonic effusion subgroup than in the neoplastic subgroup (P < 0.0002; 6.6 +/- 2.7 mgl(-1) and 1 +/- 0.2 mg l(-1), respectively). Pleural fluid CRP levels >30 mg l(-1) ! had a high sensitivity (93.7%) and specificity (76.5%) and a positive predictive value of 98.4%. In the differential diagnosis of pleural effusions, higher CRP levels may prove to be a rapid, practical and accurate method of differentiating parapneumonic effusions from other exudate types. Although the high level of CRP obtained in the exudate group may be due to the number of patients with parapneumonic effusion who were included, the pleural CRP level may also be helpful in discriminating between exudative and transudative pleural effusions.Öğe Use of pleural fluid C-reactive protein in diagnosis of pleural effusions (vol 94, pg 432, 2003)(W B Saunders Co Ltd, 2003) Turay, ÜY; Yildirim, Z; Türköz, Y; Biber, Ç; Erdogan, Y; Keyf, AI; Ugurman, F[Abstract Not Available]Öğe Vascular endothelial growth factor levels are increased and associated with disease activity in patients with Behcet's syndrome(Wiley, 2003) Çekmen, M; Evereklioglu, C; Er, H; Inalöz, HS; Doganay, S; Türköz, Y; Özerol, IHBackground/aims Vascular endothelial growth factor (VEGF) is a cytokine participating in inflammation with potent endothelial cell effects. It is produced by macrophages, neutrophils and vascular endothelial cells and can alter vessel permeability. Behcet's syndrome is a systemic inflammatory disorder with unknown etiology. Vascular endothelial dysfunction is one of the prominent features of the disease. We previously demonstrated the possible involvement of proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, soluble interleukin-2 receptor (sIL-2R), interleukin (IL)-6 and IL-8], nitric oxide (NO) and adrenomedullin in the etiopathogenesis of Behcet's syndrome. Since VEGF expression is induced by these cytokines and VEGF itself is a potent stimulator of NO production with endothelial cell effects, this study aimed to investigate whether VEGF was affected during the course of Behcet's syndrome. We also assessed the possible involvement of VEGF in ocular Behcet's syndrome or in disease activity. Methods This multicenter case-control study included a total of 39 patients with active (n = 22) or inactive (n = 17) Behcet's syndrome (mean age, 38.1 +/- 10.4 years; 21 men and 18 women) satisfying International Study Group criteria, and 15 healthy hospital-based control volunteers (mean age, 39.2 +/- 9.3 years; eight men and seven women) matched for age and gender from a similar ethnic background. Patients were examined by a dermatologist and an ophthalmologist with an interest in Behcet's syndrome. Plasma VEGF concentrations were measured using a newly established enzyme-linked immunosorbent assay. Clinical findings and acute-phase reactant parameters such as erythrocyte sedimentation rate, alpha(1)-antitrypsin, alpha(2)-macroglobulin, and neutrophil count were used to classify the disease in Behcet's patients as active or inactive. The Wilcoxon test or the Mann-Whitney U-test was used for statistical analysis as indicated and the results were expressed as mean +/- SD, with range. Results The mean plasma VEGF level in patients with Behcet's syndrome (291.9 +/- 97.1 pg/mL; range 121-532 pg/mL) was higher than that in control subjects (103.0 +/- 43.6 pg/mL; range 25-187 pg/mL) and the difference was significant (P < 0.001). Patients with active disease had significantly (P < 0.001) higher VEGF levels than patients with inactive disease (347.6 +/- 87.1 vs. 219.9 +/- 51.6 pg/mL). In addition, ocular Behcet's patients (n = 23) had higher VEGF levels (315.7 +/- 92.1 pg/mL) than nonocular patients (n = 16, 257.8 +/- 96.6 pg/mL) and the difference was of borderline significance (P = 0.041). The levels of all acute-phase reactant parameters were significantly higher in the active stage than in the inactive stage (for each, P < 0.01) or in control subjects (for each, P < 0.001). Conclusions VEGF may participate in the course of Behcet's syndrome, especially in the active stage, and elevated levels of VEGF may be an additional risk factor for the development of ocular disease, contributing to poor visual outcome.