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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 Cytokine profile and nitric oxide levels in sera from patients with brucellosis(Assoc Bras Divulg Cientifica, 2004) Refik, M; Mehmet, N; Durmaz, R; Ersoy, YThe aims of this study were to investigate the serum levels of some cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-2R, IL-6, and IL-8] and nitric oxide (NO) levels in patients with untreated brucellosis and to test the correlation of these parameters with each other. The study was conducted on 67 subjects, 37 patients with brucellosis and 30 healthy individuals with no history of Brucella infection. Brucellosis was identified by a positive blood culture and/or increased Brucella antibodies in serological tests in addition to compatible clinical symptoms. Cytokine profile analysis was performed by the immulite chemiluminescent enzyme immunometric assay whose inter- and intra-assay coefficients of variance were 2.6-3.6 and 4.4-8.5%, respectively. The levels of nitrites/nitrates, which are representative of NO levels, were measured by the Griess method. Patients with brucellosis had significantly elevated serum levels of nitrites/nitrates, IL-2R, IL-6 and IL-8 (mean +/- SD, 102.8 +/- 23.8 mumol/l, 806.1 +/- 58.5 U/ml, 21.1 +/- 2.3 mug/ml, and 8.8 +/- 1.6 pg/ml, respectively) compared to healthy controls, whereas TNF-alpha and IL-1beta levels were unchanged. No statistically significant correlation was detected between any of the studied cytokine levels and nitrate/nitrite concentrations according to Pearson's linear correlation test. We conclude that only IL-6, IL-8 and IL-2R are elevated in brucellosis and the extent of elevation depends on the severity and clinical pattern of the disease. Moderate elevation in serum NO was comparable to that observed in previous studies. This explains the absence or very rare occurrence of septic shock in brucellosis.Öğe Effects of long-term solvent exposure on blood cytokine levels and antioxidant enzyme activities in house painters(Taylor & Francis Inc, 2002) Karagözler, AA; Mehmet, N; Batçioglu, KThe aim of this study was to examine solvent-associated effects on blood cytokine levels, antioxidant enzyme activities, and malondialdehyde (MDA) concentration in house painters. Trace element (Cu and Zn) and nitrite and nitrate levels as well as protein concentrations in erythrocytes and serum were determined. Thirty male house painters and 30 male clerical workers were included in the study. There were 13 smokers and 17 nonsmokers in each group. Hemoglobin concentrations were significantly lower in house-painter blood compared to controls. House painters had significantly higher concentrations of erythrocyte protein (excluding hemoglobin), whereas no significant difference was observed between serum protein levels. Proinflammatory cytokine levels, such as tumor necrosis factor-alpha and interleukin-8, were significantly increased in house painters' sera. Interleukin-6 was below the detection limit of the assay in both groups. Interleukin-1beta and cytokine receptor interleukin 2R concentrations were not significantly affected. Furthermore, a three- to fourfold increase in nitrite and nitrate concentrations was found in house painters' sera. Serum superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities were significantly lower in house painters compared to controls. Malondialdehyde (MDA) concentration, a measure of lipid peroxidation, was found to be significantly elevated. In house painters, erythrocyte carbonic anhydrase and catalase activities were elevated approximately 11- fold and 2-fold, respectively. Zinc levels were significantly decreased in house painters' sera. Smoking was not found to be a major confounder for the association between solvent exposure and blood parameters.Öğe Lipid peroxidation and antioxidant status in stomach cancer(Taylor & Francis Inc, 2006) Batcioglu, K; Mehmet, N; Ozturk, IC; Yilmaz, M; Aydogdu, N; Erguvan, R; Uyumlu, BBackground: Considerable evidences have linked oxidative damage and cancer. In this article, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) activities, and malondialdehyde (MDA) and nitric oxide metabolites' levels (NOx) were investigated in patients with stomach cancer. Methods: All measurments were done by spectrophotometric techniques. Results: We observed a significant decrease in the activities of SOD and CAT in tumour tissues when compared with control tissues. The different of GSHPx activities and NO metabolite' levels were not statistically significant. MDA levels were significantly increased. Conclusions: We conclude that increased MDA levels and decreased antioxidant enzyme activities can be valuable parameters in assessing the possible risk of cancer.Öğe Postoperative changes in serum cytokines profile and nitric oxide levels in patients with cystic echinococcosis(Edp Sciences S A, 2005) Refik, M; Mehmet, N; Durmaz, RThe aim of the present study was to examine serum cytokines and nitric oxide (NO) levels in patients with cystic echinococcosis (CE). 28 patients with CE were studied and all underwent surgery. Serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin IL-1 beta, receptor of soluble IL-2R (sIL-2R), IL-6, IL-8, nitrate/nitrite, and C-reactive protein (CRP) were determined before and after induction of treatment. Data were compared with those obtained from 28 healthy volunteers. IL-6 was elevated in all CE patients (100 %). IL-8 was increased in 11/28 (39.3 %). Increased levels of IL-2R and TNF-alpha were found in a limited number of them particularly those showing cysts in the central area of the liver (5/28, 6/28). IL-1 beta level was not elevated in any patient except in secondary severe CE. CRP and nitrate/nitrite levels were also increased. A positive correlation between CRP and IL-6 (r = 0.74; p < 0.001) was found confirming the link between inflammation due to CE and activation of monocytes. All patients completely recovered and the levels of the studied parameters reverted to normal levels except one patient in whom severe recurrent disease occurred two years after the first operation. These results suggest that there are different immunoregulatory events and cytokines response during CE and may be in part related to slight monocytosis and in part to Th2 activation. IL-6, NO and CRP were unambiguously involved in the host parasite interaction and therefore may be useful markers in monitoring CE management and evaluating surgical stress.Öğe The role of nitric oxide and cytokines in asthma-like syndrome induced by sulfur dioxide exposure in agricultural environment(Elsevier, 2003) Koksal, N; Yildirim, Z; Gokirmak, M; Hasanoglu, HC; Mehmet, N; Avci, HBackground: We previously demonstrated that apricot sulfurization workers are exposed to high concentrations of SO2, subsequently causing asthma-like syndrome. This study investigated the effects of SO, exposure on serum TNF-alpha, IL-1beta, IL-6, IL-8, nitrite and nitrate levels to understand the mechanism of SO-induced bronchoconstriction in asthma-like syndrome. Methods: We measured the serum levels of the cytokines, direct nitrite, total nitrite and nitrate obtained from 40 volunteer workers after an hour of exposure to SO2 and 23 healthy controls. Results: The concentrations of the cytokines, direct nitrite, total nitrite and nitrate were significantly (p < 0.0001) higher in the workers than in the controls. The mean serum concentrations of TNF-alpha, IL-1beta, IL-6, IL-8, direct nitrite, total nitrite and nitrate were 430.60 +/- 397.03 pg/ml, 436.67 +/- 316.31 pg/ml, 752.11 +/- 394,95 pg/ml, 262.12 +/- 287.99 pg/ml, 7.75 +/- 3.34 mumol/l, 115.72 +/- 48.78 mumol/l and 107.97 +/- 46.19 mumol/l in the workers, while they were 9.83 +/- 3.12 pg/ml, < 5 pg/ml, 7.49 +/- 1.27 pg/ml, 9.38 +/- 1.99 pg/ml, 2.17 +/- 0.77 mumol/l, 59.91 +/- 7.56 mumol/l and 57.74 +/- 7.20 mumol/l in the controls, respectively. Conclusion: These results show that TNF-alpha, IL-1beta, IL-6, IL-8 and nitric oxide may play a role in the pathogenesis of bronchoconstriction in asthma-like syndrome due to the SO2 exposure. (C) 2003 Elsevier B.V. All rights reserved.Öğe The role of oxidative stress in bronchoconstriction due to occupational sulfur dioxide exposure(Elsevier, 2003) Gokirmak, M; Yildirim, Z; Hasanoglu, HC; Koksal, N; Mehmet, NBackground: We previously showed that apricot sulfurization workers (ASW) are exposed to high concentrations of SO2, resulting in an asthma-like syndrome. The aim of this study was to evaluate whether oxidative stress plays a role in the pathogenesis of asthma-like syndrome due to the high concentrations of SO2 exposure in agricultural environment. Methods: Serum antioxidant enzyme activities and malondialdehyde (MDA) concentrations, which are markers of lipid peroxidation, and pulmonary function tests (PFT) were measured in 40 volunteer ASW and compared to 20 healthy control subjects. Results: The superoxide dismutase (SOD, 2.2 +/- 0.6 vs. 3.2 +/- 0.7 U/m), glutathione peroxidase (GSH-Px, 0.6 +/- 0.3 vs. 1.1 +/- 0.3 U/m) and catalase (107.6 +/- 27.4 vs. 152.6 +/- 14.3 k/l) activities in ASW were significantly (p < 0.0001) lower than controls, whereas the malondialdehyde concentration (4.1 +/- 0.9 vs. 1.9 +/- 5.3 nmol/l) was higher in ASW (p < 0.0001). ASW had significant decreases in pulmonary function parameters after exposure. Conclusion: These results show that occupational exposure to high concentrations of SO2 enhances oxidative stress and lipid peroxidation may be considered as a new mechanism of SO2-induced bronchoconstriction. (C) 2003 Elsevier Science B.V. All rights reserved.Öğe Serum and gastric fluid levels of cytokines and nitrates in gastric diseases infected with Helicobacter pylori(Luigi Ponzio E Figlio, 2004) Mehmet, N; Refik, M; Harputluoglu, M; Ersoy, Y; Aydin, NE; Yildirim, BThis case control study presents data on the concentrations of nitrite and nitrate and a variety of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor TNF-alpha in gastric fluid and serum. Patients with gastritis, gastric ulcer and gastric cancer are studied and grouped according to infection by Helicobacter pylori. The 208 patients who underwent tipper gastrointestinal endoscopic examination were classified as follows; H. pylori-positive gastritis (n=32), H. pylori-negative gastritis (n=32), H. pylori-positive ulcers (n=34), H. pylori-negative ulcers (n=34), 43 patients with H. pylori-positive gastric cancer in addition to 33 H. pylori-negative healthy control individuals. Gastric fluids and blood samples were taken concomitantly. Cytokines and nitrite and nitrate determinations were attempted as soon as possible after collection of the samples. Nitrite and nitrate levels of serum and gastric fluids of H. pylori-positive gastritis and ulcers were higher than H. pylori-negative gastritis and ulcers. The concentrations of total nitrite and nitrate and cytokines (TNF-alpha IL-2R, IL-6, and IL-8) in gastric fluids and sera of H. pylori-positive gastric cancer patients were higher than H. pylori-negative control groups. IL-1beta level was significantly elevated in gastric fluid of infected cancer patients but not in serum. Taken together, the results suggest that an increase in cytokine-NO combination in gastric mucosa previously reported by many studies is not restricted to local infected gastric tissue but also detected in gastric fluid and sera of H. pylori-positive subjects and may have an important role in the pathogenesis and development of common gastric diseases.Öğe Serum cytokine changes in Turkish children infected with Giardia lamblia with and without allergy(Elsevier Science Bv, 2005) Bayraktar, MR; Mehmet, N; Durmaz, RThe present report is a case control study aimed to determine the levels of cytokines and other parameters in the sera of allergy-complicated and uncomplicated giardiasic children before and after metronidazole treatment. The study included a total of 126 subjects; 52 giardiasic children, 34 allergy-complicated giardiasis (36.9%) and 34 healthy controls, as well as six cases of giardiasis simultaneously infected with other parasites or bacterial pathogens. Serum levels of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1 beta, soluble IL-2 receptor (sIL-2R), IL-6, IL-8, nitric oxide (NO), and C-reactive protein (CRP) were determined. TNF-alpha and sIL-2R levels significantly increased in giardiasic cases. IL-1 beta, IL-6, IL-8, CRP, and NO levels increased only in the cases associated with allergy. All increased variables significantly decreased following metronidazole treatment and returned to normal levels. Metronidazole-treated patients became 100% parasite free. In conclusion, increased TNF-alpha and sIL-2R may be involved in pathogenesis of non-allergic giardiasis and probably Th1 type immune response seems to be predominant and this response may be protective rather than causative of the disease. Activation of the immune system takes place in giardiasis. It is broader and more intense in allergy-complicated giardiasis than that of uncomplicated cases, most probably due to non-invasive character of G. lamblia. Enhanced IgE production pointed to Th2-type immune response and confirms its association with allergy. (C) 2005 Elsevier B.V. All rights reserved.Öğe Serum nitrite and nitrate levels in epileptic children using valproic acid or carbamazepine(Elsevier Science Bv, 2004) Karabiber, H; Yakinci, C; Durmaz, Y; Temel, I; Mehmet, NIn experimental epilepsy studies, nitric oxide was found to act as both proconvulsant and anticonvulsant. The objective. of this study was to investigate the effects of valproic acid and carbamazepine on serum levels of nitrite and nitrate, which are the metabolites of nitric oxide. To achieve this goal, serum nitrite and nitrate levels were determined in active epileptic 34 children using valproic acid and 23 children using carbamazepine and in non-active epileptic 38 children (control group) not using any antiepileptic drug. In the valproic acid group serum nitrite and nitrate levels were 2.66 +/- 2.11 mumol/l and 69.35 +/- 23.20 mumol/l, 1.89 +/- 1.01 mumol/l and 49.39 +/- 10.61 mumol/l in the carbamazepine group, and 1.22 +/- 0.55 mumol/l, 29.53 +/- 10.05 mumol in the control group, respectively. Nitrite and nitrate levels were significantly high in both valproic acid and carbamazepine groups compared to the control group (P < 0.01). When valproic acid and carbamazepine groups were compared to each other, level of nitrate was found statistically higher in the valproic acid group in relation to the carbamazepine group (P < 0.01), however, there was no statistically significant difference in the levels of nitrite (P > 0.05). No relation could be found between serum drug levels and nitrite and nitrate levels. According to these results, it can be suggested that valproic acid and carbamazepine might have antiepileptic effects through nitric oxide. (C) 2003 Elsevier B.V. All fights reserved.Öğe Urinary nitric oxide levels are increased and correlated with plasma concentrations in patients with Behcet's disease(Wiley, 2003) Evereklioglu, C; Özbek, E; Çekmen, M; Mehmet, N; Duygulu, F; Ozkiris, A; Çalip, MNitric oxide ( NO) is a free radical and serves many functions within the kidney. Excess NO causes glomerular injury. Behcet's disease (BD) is a systemic immunoinflammatory vasculitis, affecting every organ in the body including the kidneys ( subclinic glomerulonephritis). We investigated the role of urinary total nitrite levels (end product of NO) in BD and evaluated whether urinary concentrations were correlated with its plasma levels or disease activity. Thirty-six consecutive Behcet's patients (19 men, 17 women; 35.9 years), and 20 age- and sex-matched healthy control volunteers (12 men, eight women; 33.2 years) were divided into an active (n = 16) and inactive ( n = 20) period. Urinary and serum NO levels (mumol/mg urinary creatinine) were higher in BD patients (4.1 +/- 0.3) than control subjects (1.7 +/- 0.2; P < 0.001). Serum NO levels in Behcet's patients and control subjects were 51.3 +/- 9.8 and 21.7 +/- 7.3 mu mol/ L, respectively (P < 0.001). Active patients had higher urinary NO excretion (4.9 +/- 0.3) than inactive patients (3.3 +/- 0.3; P < 0.01). Urinary NO levels were correlated with its serum levels (r(2) = 0.69, P < 0.001). Higher urinary NO levels found in BD may be produced by the kidney as a result of an inflammatory stimulation. As excess NO is toxic to the tissues, increased NO levels may play a role in mediating subclinic glomerular injury of such patients. However, we could not determine the exact site(s) of NO synthesis by the kidney, such as the glomeruli, blood vessels and/or the tubular cells. Whatever the source, urinary NO levels may be used as a new activity marker in the diagnosis and follow up of BD by serial measurements.
