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Öğe Adrenomedullin and nitrite levels in children with Bartter syndrome(Springer-Verlag, 2000) Balat, A; Çekmen, M; Yürekli, M; Kutlu, O; Islek, I; Sönmezgöz, E; Çakir, MChildren with Bartter syndrome have lower than normal vascular reactivity with normotension in spite of biochemical and hormonal abnormalities which are typical of hypertension. Nitric oxide (NO) is a potent endogenous vasodilator, and plays an important role in the control of vascular tone. Adrenomedullin (AM) is a novel hypotensive peptide originally isolated from human pheochromocytoma. The possible role of NO and PLM in maintaining this reduced vascular reactivity was examined by studying plasma and urinary nitrite, a stable metabolite of NO, and AM levels in ten children with Bartter syndrome, ten healthy controls, and five children with hypokalemia of causes other than Bartter syndrome (pseudo-Bartter). Urinary excretion of nitrite (mu mol/mg urinary creatinine) was 8.9.+/-1.2 in children with Bartter syndrome, 4.7.+/-0.9 in healthy controls, and 2.9.+/-0.8 in pseudo-Bartter (P<0.05). Plasma nitrite levels (mol/l) were 101.9+/-23.4, 59.9+/-14.7, and 65.0+/-29.7, respectively (P>0.05), in the three groups. Urinary excretion of AM (pmol/mg urinary creatinine) was 187+/-40, 65+/-10, and 160+/-50, respectively (P<0.05), in the three groups. Plasma AM levels were 47.4+/-1.8, 39.9+/-5.9, and 42.4+/-3.9, respectively (P>0.05), in the three groups. The same parameters were repeated in the two groups of controls and in the Bartter patients in the 6th month of therapy. Urinary nitrite and AM levels were still higher in the Bartter patients than in the other groups. We conclude that in Bartter syndrome the increased NO production may be responsible for the reduced vascular response of the disease. Initially, increased levels of AM in Bartter syndrome and pseudo-Bartter may be a compensatory response to acute hypokalemia; however, continuation of a high level of urinary excretion of AM in children with Bartter syndrome may suggest also the possible role of AM in the reduced vascular response of the disease.Öğe Adrenomedullin and nitrite levels in children with dilated cardiomyopathy(Springer-Verlag, 2003) Kilinç, M; Balat, A; Çekmen, M; Yürekli, M; Yilmaz, K; Sahinöz, SDilated cardiomyopathy (DCM) is an important cause of chronic congestive cardiac failure in children. In patients with idiopathic DCM, endothelium vasomotor function is disturbed. There are many studies on the roles of nitric oxide (NO) and adrenomedullin (AM) in adult patients with DCM. However, to our knowledge, no studies have investigated the level of AM and NO in children with idiopathic DCM. We determined plasma and urinary AM and total nitrite concentrations in children with idiopathic DCM and investigated the correlation between these and other clinical and laboratory findings. Eleven patients with DCM, ranging in age from 5 month to 14 years, were compared to 10 healthy age- and sex-matched controls. Plasma (pmol/ml) and urinary (pmol/mg creatinine) AM levels were significantly lower than in the healthy controls (19.55 +/- 2.36 vs 51.61 +/- 7.22 and 28.29 +/- 20.66 vs 68.87 +/- 40.23, respectively; p < 0.001). Plasma and urinary AM levels were negatively correlated with ejection fraction (EF) and fractional shortening (FS). The plasma (Mmol/L) and urinary nitrite levels (Mmol/mg creatinine) were not different between patients and controls [50.90 +/- 17.50 vs 53.40 +/- 26.05 (p > 0.05) and 1.98 +/- 1.24 vs 2.75 +/- 1.68 (p > 0.05), respectively]. In our study, the first to analyze AM and nitrite levels in children with DCM, plasma and urinary AM levels were found to be decreased. A possible explanation for this reduction could be depletion of the viable myocyte population. However, this hypothesis must be clarified by further studies.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 Adrenomedullin and nitrite levels in children with primary nocturnal enuresis(Springer, 2002) Balat, AE; Çekmen, M; Yürekli, M; Gül, AK; Özbek, E; Korkut, M; Tarakçioglu, MPrimary nocturnal enuresis (PNE) is the most common type of nocturnal enuresis in children, but its etiology remains unclear. Recent studies indicated the differences in urinary electrolytes in enuretic children, and stressed the existence of a renal tubular maturation defect. In this study, 30 children (aged 6-12 years) with PNE were investigated in comparison with 18 healthy controls. We evaluated plasma antidiuretic hormone, electrolytes, 24-h urine volume, osmolarity, and urinary electrolytes. Unlike other studies, we firstly assessed the plasma and urinary adrenomedullin (AM) and total nitrite levels, a stable product of nitric oxide (NO), and investigated their relationship with urinary electrolytes. The plasma AM and total nitrite levels were significantly lower than controls. Urine volume (24-h) and potassium excretion were higher than in controls. However, 24-h urinary osmolarity and excretion of AM were significantly lower than in controls. Our results indicate that there may be a problem in renal regulation of potassium in children with PNE. Although decreased levels of AM and total nitrite may be a compensatory response to abnormal potassium and water excretion, further investigations are required to exclude whether the renal synthesis of AM and NO are also deficient in these children.Öğe Adrenomedullin and total nitrite levels in children with familial Mediterranean fever(Blackwell Publishing, 2006) Balat, A; Islek, I; Çekmen, M; Yürekli, M; Tekin, D; Muslu, A; Sahinöz, SAim: Familial Mediterranean fever (FMF) is the most frequent periodic syndrome characterised by recurrent attacks of polyserositis. However, recent studies revealed that there might be an ongoing subclinical inflammation between the attacks. As nitric oxide (NO) and adrenomedullin (AM) are both synthesised in the endothelium, and mediates many functions within immune system, we considered them to be an interesting target of investigation in FMF. Methods: Fifteen children with FMF receiving regular colchicine, ranging in age from 3 to 16 years, were investigated in comparison with 15 healthy age- and sex-matched controls. The mean age of the patients was 9.7 +/- 3.9 years. Total nitrite, a stable product of NO, was quantitated by means of the Griess reaction, while AM was measured by HPLC. Results: Plasma-urinary AM and total nitrite levels were significantly higher in children with FMF. Plasma AM levels (pmol/mL) in patients and controls were 40.95 +/- 5.99 vs. 34.86 +/- 5.24, P < 0.05, and urinary AM excretion (pmol/mg creatinine) was 51.16 +/- 28.15 vs. 37.5 +/- 24.26, P < 0.05 respectively. Plasma total nitrite levels (mu mol/L) in patients and controls were 44.80 +/- 10.36 vs. 32.13 +/- 9.28, P < 0.05, and urinary nitrite excretion (mu mol/mg creatinine) was 2.24 +/- 1.71 vs. 1.09 +/- 0.96, P < 0.05 respectively. Conclusion: This study considered that AM and NO may have a role in the immuno-inflammatory process of FMF, although, whether these act to preserve, or protect against, further inflammatory injury is not clear. Our results further supports the hypothesis that these patients have subclinical inflammation between attacks.Öğe Adrenomedullin and total nitrite levels in children with Henoch-Schonlein purpura(Springer, 2003) Islek, I; Balat, A; Çekmen, M; Yürekli, M; Muslu, A; Sahinöz, S; Sivasli, ENitric oxide (NO) is synthesized from endothelium and has an important role in the control of vascular tonus. Adrenomedullin (AM) is a potent vasodilator, and cytoprotective peptide is produced not only in adrenal medulla, but also in the vascular smooth muscle and endothelial cells. To investigate the endothelial synthesis of AM and NO, and endothelial injury in Henoch-Schonlein purpura (HSP), we measured their levels in 16 children with HSP, who were evaluated during the acute and remission phases, and compared with 12 healthy controls. Plasma AM levels (pmol/ml) were significantly higher in acute phase children (46.87+/-11.49) than in those in remission (35.59+/-12.39, p<0.01) and controls (30.70+/-9.12, p<0.001). Similarly, plasma total nitrite levels (mumol/l) were higher in acute phase patients (47.50+/-12.30) than in those in remission (35.94+/-10.08, p<0.005) and controls (34.56+/-11.51, p<0.05). Urinary excretion of AM (pmol/mg creatinine) was higher in acute phase patients (53.85+/-23.22) than in remission patients (29.97+/-9.33, p<0.01) and controls (37.43+/-15.78, p<0.05). Patients had increased urinary nitrite excretion (mumol/mg creatinine) in acute phase (2.39+/-1.18) compared to those in remission (1.53+/-0.90, p<0.05) and controls (1.05+/-0.61, p<0.005). There was no significant difference between remission phase and controls in AM and nitrite levels (p>0.05). This study concluded that AM and NO may have a role in the immunoinflammatory process of HSP, especially in the active stage, although whether this perpetuates, or protects against, further vascular injury is not clear. Further studies are needed to clearly establish the roles of AM and NO in the pathogenesis of HSP.Öğe Is there a change in serum CA-125 levels after laparoscopy?(I R O G Canada, Inc, 2004) Atmaca, R; Balat, O; Ugur, MG; Çekmen, M; Kutlar, I; Aksoy, FThere is no adequate data in the medical literature defining serum CA-125 levels after laparoscopy. Therefore we designed this prospective study to evaluate the effects of laparoscopy on serum CA-125 levels. Eighty-two women (mean age 34.2 +/- 12.30 years) were included in the study between January, 2001 and April, 2003. Laparoscopies were performed in patients with chronic pelvic pain, dysmenorrhea, infertility, ovarian cysts and for tubal ligation. Mean serum CA-125 levels of the patients before and after the laparoscopic procedures were 13.96 +/- 4.86 U/ml and 14.02 +/- 4.96 U/ml, respectively. The change in serum CA-125 levels prior to laparoscopy was statistically insignificant when compared with the levels obtained at 24 hours after laparoscopic procedure (p > 0.05). We found that diagnostic laparoscopy or laparoscopic surgical procedures did not change the levels of CA-125 at the 24th hour after laparoscopy indicating either serum CA-125 levels are not correlated, at least within 24 hours, with peritoneal irritation or peritoneal irritation is minimal or absent in our operations.Öğe Serum leptin concentrations are decreased and correlated with disease severity in age-related macular degeneration(Nature Publishing Group, 2003) Evereklioglu, C; Doganay, S; Er, H; Çekmen, M; Özerol, E; Otlu, BBackground Age-related maculopathy (ARM) or degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. Despite several studies on the morphology of ARMD, the aetiology is unknown and factor(s) contributing to the pathogenesis remain to be characterised. More recent studies have demonstrated that cholesterol esters and lipids are present within Bruch's membrane deposits and drusen, and dietary fat intake is associated with ARMD. The product of Ob gene, leptin, is a recently discovered peptide participating in human metabolism. There is a direct relationship between serum leptin and diet, and lipoprotein metabolism, but the role of leptin in the course of ARMD has not previously been investigated. Purpose This cross-sectional case-control study investigated whether serum leptin level was associated with ARMD as a new possible risk factor and to assess its relationship with disease severity. Methods A total of 32 patients with ARM or ARMD (17 men, 15 women) and 20 age- and sex-matched healthy control subjects without ARMD (11 men, nine women) from a similar ethnic background were enrolled in this multicentre study. Body mass index (BMI) (weight (kg)/height (m(2))) was calculated for each group. The presence of maculopathy was assessed on the basis of colour fundus photographs using an international classification system. Patients were classified as early-ARM (n = 16) or late-ARMD (n = 16) using clinical examination and grading of photographs. Serum leptin levels were measured by an enzyme-linked immunosorbent assay kit. The Mann-Whitney U test or chi(2) test was used for statistics as indicated, and P<0.05 was considered to be significant. Results The age, sex ratio, and BMI between groups were comparable. Patients with maculopathy had significantly (P<0.001) lower leptin levels (mean +/- SD, 6.01 +/- 2.55 ng/ ml) than control subjects (13.21+/- 2.27 ng/ml). In addition, late-ARMD patients had significantly lower leptin levels (3.81 +/- 0.58 ng/ ml) than early-ARM patients (8.21 +/- 1.68 ng/ml, P<0.001) or control subjects (P<0.001). Conclusion Leptin seems to be a possible newly associated factor in the course of ARM and may be involved in the lipid composition of the macular lesions, especially in late-ARMD.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 Urinary adrenomedullin levels are increased and correlated with plasma concentrations in patients with Behcet's syndrome(Wiley-Blackwell, 2002) Evereklioglu, C; Özbek, E; Er, H; Çekmen, M; Yürekli, MBackground: The objective was to measure urinary adrenomedullin (AM) levels in patients with active or inactive Behcet's syndrome and compare them to levels in healthy control subjects. Methods: Forty-five consecutive patients with Behcet's syndrome (20 men and 25 women with a mean age of 37.7 +/- 10.8 years) and 20 age- and sex-matched healthy hospital staff volunteers as control subjects (nine men and 11 women with a mean age of 36.2 +/- 10.4 years) were studied. Urinary and plasma AM concentrations were measured by high-performance liquid chromatography. We also investigated whether disease activity correlates with urinary and plasma AM levels. The Mann-Whitney U -test was used in statistical analysis and the values were expressed as mean +/- SD. Results: Urinary excretion of AM (pmol per mg urinary creatinine) in patients with Behcet's syndrome (81.3 +/- 35.1) was significantly higher (P < 0.001) than in control subjects (31.2 +/- 16.1). Plasma AM levels (pmol/L) in patients with Behcet's syndrome and controls were 69.1 +/- 19.2 and 20.7 +/- 11.8, respectively; the difference was significant (P < 0.001). Although active Behcet's syndrome patients (n = 22) had higher urinary AM levels (92.1 +/- 41.1) compared to inactive (n = 23; 70.8 +/- 32.2), the difference was not significant (P > 0.05). Plasma AM levels in active Behcet's syndrome patients (77.5 +/- 21.2) were also higher than in inactive (61.6 +/- 17.3), but the difference was not significant (P > 0.05). Conclusion: Urinary AM levels were higher in Behcet's patients than in control subjects. Urinary AM levels were correlated with plasma AM levels. The results suggest that the higher AM levels found in the urine may be produced by the kidney as a result of the stimulation of inflammation during the course of Behcet's syndrome, or may come from plasma, as plasma AM levels were increased. However, the exact sites of AM synthesis by the kidney (e.g. glomeruli, blood vessels and/or tubular cells) could not be determined in this study. Further studies in this respect are necessary.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.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.