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The aim of this study is to investigate the association of perifollicular blood flow (PFBF) with follicular fluid EG-VEGF, inhibin-a, and insulin-like growth factor-1 (IGF-1) concentrations, endometrial vascularity, and IVF outcomes. Forty women with tubal factor infertility were included in a prospective cohort study. Each woman underwent IVF/ICSI procedure. Individual follicles of ≥16 mm (n = 156) were evaluated by power Doppler analysis and categorized as well-vascularized follicles (WVFs) or poorly vascularized follicles (PVFs). WVFs referred to those with perifollicular vascularity of 51–100 %. Each follicular fluid (FF) was individually aspirated and FF/serum EG-VEGF, inhibin-a, and FF IGF-1 levels were evaluated. Zones III–IV endometrial vascularity was classified as a well-vascularized endometrium (WVE). The presence of a WVE and mature oocytes, in addition to the embryo quality and clinical pregnancy rate (CPR), were recorded for each follicle. The main outcome measures were FF serum EG-VEGF, inhibin-a, IGF-1 levels, and WVE and IVF outcome per PFBF. For WVFs, the level of FF EG-VEGF (p = 0.008), oocyte quality (p = 0.001), embryo quality (p = 0.002), a WVE (p = 0.001), and CPR (p = 0.04) increased significantly. The pregnant group was characterized by increased numbers of WVFs (p = 0.044), a WVE (p = 0.022), and increased levels of FF IGF-1 (p = 0.001) and serum EG-VEGF (p = 0.03). FF IGF-1 >50 ng/mL (AUC 0.72) had 75 % sensitivity and 64 % specificity for predicting CPR. WVFs yield high-quality oocytes and embryos, a WVE, increased FF EG-VEGF levels, and increased CPRs.

Purpose: In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). Methods: Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. Results: The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. Conclusion: We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP.

Endothelial dysfunction and microvascular damage play a crucial role in the pathogenesis of erectile dysfunction (ED). Lp-PLA2 is a calcium-independent member of the phospholipase A2 family and hydrolyses oxidised phospholipids on low-density lipoprotein (LDL) particles that plays a pivotal role in ox-LDL-induced endothelial dysfunction. The purpose of the current study was to determine the association between Lp-PLA2 levels and ED in patients without known coronary artery disease (CAD). All patients were evaluated for ED and divided into two groups: 88 patients suffering from ED for >1 year were enrolled as an experimental group and 88 patients without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. Levels of Lp-PLA2 were measured in serum by colorimetric assay. The relationship between Lp-PLA2 levels and ED in patients was evaluated statistically. The mean age of patients with ED group was 59.4 ± 11.32 and 55.8 ± 9.67 in the control group. Plasma Lp-PLA2 levels were significantly higher in ED than in the control group (220.3 ± 66.90 and 174.8 ± 58.83 pg ml(-1) , respectively, P < 0.001). The Lp-PLA2 levels were negatively correlated with score of ED (r = -0.482, P < 0.05). In logistic regression analysis, enhanced plasma Lp-PLA2 levels result in approximately 1.2-fold increase in ED [1.22 (1.25-2.76)]. In this study, serum Lp-PLA2 levels were found to be associated with endothelial dysfunction predictive of ED. Serum Lp-PLA2 level appears to be a specific predictor of ED, and it may be used in early prediction of ED in the male population.

Objectives Vertigo is a common presenting complaint resulting from central or peripheral etiologies. Because central causes may be life-threatening, ascertaining the nature of the vertigo is crucial in the emergency department (ED). With a broad range of potential etiologies, distinguishing central causes from benign peripheral causes is a diagnostic challenge. Cranial magnetic resonance imaging (MRI) is the recommended neuroimaging method when clinical findings are ambiguous. However, MRI scanning for every patient with an uncertain diagnosis may not be efficient or possible. Therefore, to improve ED resource utilization for patients with vertigo, there is a need to identify the subset most likely to have MRI abnormalities. It has previously been shown that S100B protein provides a useful serum marker of stroke, subarachnoid hemorrhage, and traumatic brain injury. This study evaluated whether S100B levels could predict central causes of vertigo as identified by cranial MRI in the ED. Methods This prospective, observational study was conducted with adult patients with acute-onset vertigo (within 6 hours) in the ED of a teaching hospital in Kocaeli, Turkey. Patients with nausea or dizziness complaints without previously known vertigo or cranial pathology, and who agreed to participate in the study, were included. Patients with trauma or with neurologic findings that developed concurrent with their symptoms were excluded. Serum levels of S100B were measured with an electrochemiluminescence immunoassay kit. All subjects underwent cranial MRI. The predictors of positive MRI results were evaluated using logistic regression analysis. Sensitivity and specificity of S100B​ levels for identifying subjects with central causes of vertigo on MRI were calculated with receiver operating characteristic (ROC) curve. Results Of the 82 subjects included in the study, 48 (58.5%) were female, and the mean (±SD) age was 51 (±16) years. Thirty-one (37.8%) subjects had positive MRI results. Median (with interquartile range [IQR]) serum S100B levels were significantly different between MRI-negative and MRI-positive groups (median = 27.00 pg/mL, IQR = 10.00 to 44.60 vs. median = 60.94 pg/mL, IQR = 38.25 to 77.95, respectively; p = 0.04). In logistic regression analysis, subjective “he or she is spinning” (p = 0.030, odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.38 to 2.49), systolic blood pressure (sBP; p = 0.045, OR = 1.044, 95% CI = 1.021 to 1.080), and serum S100B level (p = 0.042, OR = 1.22, 95% CI = 1.018 to 1.445) were found to be independent predictors of MRI abnormalities. In the ROC analysis, S100B > 30 pg/mL predicted the clinical outcome with 83.9% sensitivity (95% CI = 66.3% to 94.5%) and 51.0% specificity (95% CI = 36.6% to 65.2%). The area under the ROC curve was 0.774 (95% CI = 0.666 to 0.881). Conclusions To the best of our knowledge this is the first study assessing the utility of serum S100B levels for diagnosis of acute-onset vertigo. Serum S100B levels are associated with the presence of central causes of vertigo on cranial MRI. However, serum S100B levels are not sufficiently sensitive to exclude candidates from cranial MRI. Resumen Objetivos El vertigo es un motivo de consulta frecuente y es consecuencia de una etiologia central o periferica. Debido a que las causas centrales pueden ser de riesgo vital, la determinacion de la naturaleza del vertigo es crucial en el servicio de urgencias (SU). Con un amplio abanico de etiologias potenciales, el distinguir las causas centrales de las perifericas benignas es un reto diagnostico. La resonancia magnetica (RM) craneal es la prueba de neuroimagen recomendada cuando los hallazgos clinicos son ambiguos. Sin embargo, la realizacion de una RM a todo paciente con diagnostico incierto puede no ser posible o eficiente. Por lo tanto, para mejorar la utilizacion de recursos del SU en los pacientes con vertigo, existe la necesidad de identificar el grupo con mayor probabilidad de tener alteraciones en la RM. Se ha demostrado previamente que la proteina S100B es un marcador serico de utilidad para el ictus, la hemorragia subaracnoidea y la lesion cerebral traumatica. Este estudio evaluo si los valores de S100B podrian predecir las causas centrales de vertigo en el SU como las identifica la RM craneal. Metodologia Estudio observacional prospectivo que se llevo a cabo en pacientes adultos con vertigo de inicio agudo (en las 6 primeras horas) en el SU de un hospital universitario en Kocaeli (Turquia). Se incluyeron los pacientes que aquejaban mareo o nauseas, sin historia previa conocida de vertigo o patologia craneal, y que consintieron participar en el estudio. Se excluyeron los pacientes con traumatismo o hallazgos neurologicos desarrollados simultaneamente con sus otros sintomas. Se midieron los valores sericos de S100B con un kit de inmunoensayo de electrofluorescencia. Se realizo RM craneal a todos los sujetos. Se evaluaron los factores predictivos de RM positiva usando un analisis de regresion logistica. Se calculo con la curva de caracteristica operativa del receptor (Receiver Operating Characteristic, ROC) la sensibilidad y la especificidad de los valores de S100B para la identificacion de sujetos con causas centrales de vertigo en la RM. Resultados De los 82 sujetos incluidos en el estudio, 48 (58,5%) fueron mujeres y la media de edad fue de 51 anos. Treinta y un pacientes (37,8%) tuvieron una RM positiva. La mediana (con rango intercuartilico [RIC]) de los valores sericos de S100B fue diferente de forma significativa entre los grupos con RM negativa y RM positiva (mediana 27,00 pg/mL [RIC 10,00 a 44,60] frente a 60,94 pg/mL [RIC 38,25 a 77,95] respectivamente, p = 0,04). En el analisis de regresion logistica, la sensacion subjetiva “que el o ella esta dando vueltas” (OR = 1,63, IC 95% = 1,38 a 2,49; p = 0,030), la presion arterial sistolica (OR = 1,04, IC 95% = 1,02 a 1,08; p = 0,045) y los valores sericos de S100B (OR = 1,22, IC 95% = 1,02 a 1,44; p = 0,042) resultaron ser predictores independientes de alteraciones en la RM. En el analisis ROC, los valores sericos de S100B > 30 pg/ml predijeron el resultado clinico con una sensibilidad de un 83,87% (IC 95% = 66,3% a 94,5%), y una especificidad de 50,98% (IC 95% = 36,6% a 65,2%). El area bajo la curva fue de 0,774 (IC 95% = 0,666 a 0,881). Conclusiones Hasta donde conocemos, este es el primer estudio que evalua la utilidad de los valores sericos de S100B para el diagnostico de vertigo de inicio agudo. Los niveles sericos de S100B se asociaron con la presencia de causas centrales de vertigo en RM craneal. No obstante, los niveles sericos de S100B no son suficientemente sensibles para excluir los candidatos a la RM craneal.

We evaluated the potential protective effect of hydrogen sulfide (H2S) against GEN-induced nephrotoxicity in rats.Twenty-four rats were randomly divided into four groups, each consisting of six animals as follows: (1) the rats were control, (2) intraperitoneally injected with GEN 14 consecutive days (100 mg/kg/day), (3) treated with GEN plus %0.9 saline intraperitoneally for 14 days and (4) treated with GEN plus sodium hydrogen sulfide (NaHS)-exogenous H2S donor (56 µmol/kg/day) for 14 days. After 15 days, rats were sacrificed and their kidneys were taken and blood analysis was performed. Twenty-four hours urine collections were obtained in standard metabolic cages a day before the rats were sacrificed. Tubular necrosis and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of kidneys. Statistical analyses were made by the chi-squared test and one-way analysis of variance.Serum urea and creatinine levels were significantly higher in rats treated with GEN alone, than the rats in control and GEN + NaHS groups. The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of NaHS to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and NaHS had significantly lower MDA and NO levels in kidney cortex tissue than those that was given GEN alone. In rats treated with GEN + NaHS, despite the presence of mild tubular degeneration and tubular necrosis are less severe, and glomeruli maintained a better morphology when compared with GEN group.We can say that H2S prevent kidney damage with antioxidant and anti-inflammatory effect.

To investigate the biochemical markers such as nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH), indicators of the oxidative status of the follicle, to predict the outcome of in vitro fertilization.Follicular aspirates of dominant follicles were collected during oocyte retrieval. Biochemical analyses of NO, MDA and GSH were performed on all aspirates.When the successful and unsuccessful pregnancy groups were compared in terms of NO, MDA and GSH, follicular fluid MDA was significantly higher (p=0.001) and follicular fluid NO level was significantly lower (p=0.039) in the pregnant group. Correlation analysis between oxidative stress and IVF parameters showed that MDA had a positive weak correlation with the number of grade 1 embryos (r=0.271, p=0.033) and fertilization rate (r=0.263, p=0.039). ROC curve analysis found that malondialdehyde has an area under the curve of 0.74 and can predict pregnancy with high sensitivity.As malondialdehyde was significantly different in pregnant and non-pregnant women and had a good sensitivity profile in predicting pregnancy, it may be considered a marker for predicting IVF success.Folikül oksidatif durumunun belirteci olan nitrik oksit (NO), malondialdehit (MDA) ve redükte glutatyon (GSH) gibi kimyasal belirteçlerinOosit toplama sırasında dominant foliküllerin aspire edilen sıvıları toplandı. Tüm aspire edilen sıvılarda biyokimyasal analiz ile NO, MDA ve GSH seviyelerine bakıldı.Gebelikle sonuçlanan ve gebe kalamayan olguların NO, MDA and GSH seviyeleri karşılaştırıldığında, folikül sıvısı MDA seviyesi gebe kalanlarda anlamlı olarak yüksek bulunurken (p=0.001), NO seviyesi ise gebe kalanlarda anlamlı olarak düşük bulundu (p=0.039). Oksidatif stres ve in vitro fertilizasyon parametreleri arasında korelasyon analizi yapıldığında, MDA ile grade 1 embriyo sayısı arasında (r=0.271, p=0.033) ve fertilizasyon oranı arasında (r=0.263, p=0.039) zayıf pozitif bir korrelasyon bulundu. ROC eğrisi analizinde MDA’nın çizgi altında kalan alanı 0.74 hesaplanarak gebe kalan olguları öngörmede yüksek bir duyarlılığı olduğu bulundu.Malondialdehit gebe kalan olguların follikül sıvılarında gebe kalamayanlardan anlamlı olarak yüksek bulunmasının yanı sıra, gebeliği öngörmede iyi bir duyarlılığa sahipti ve IVF olgularında gebeliği öngörmede bir belirteç olarak kullanılabilir.

Nephrotoxicity is a major complication of gentamicin (GEN). We aimed to evaluate the potential protective effect of montelukast (MK) against GEN-induced nephrotoxicity in rats. Thirty-two rats were randomly divided into four groups, each consisting of eight animals as follows: (1) the rats were control; (2) intraperitoneally injected with GEN 14 consecutive days (100 mg/kg/day); (3) treated with GEN plus distilled water via nasogastric gavage for 14 days; and (4) treated with GEN plus MK (10 mg/kg/day) for 14 days. After 15 days, rats were killed and their kidneys were taken and blood analysis was performed. Twenty-four hours urine collections were obtained in standard metabolic cages a day before the rats were killed. Tubular necrosis and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in the other part of kidneys. Statistical analyses were made by the chi-square test and analysis of variance. Serum urea and creatinine levels were significantly higher in rats treated with GEN alone, than the rats in control and GEN + MK groups.The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of MK to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and MK had significantly lower MDA and NO levels in kidney cortex tissue than those that was given GEN alone. In rats treated with GEN + MK, despite the presence of mild tubular degeneration and tubular necrosis are less severe, and glomeruli maintained a better morphology when compared with GEN group. We can say that MK prevents kidney damage with antioxidant effect, independently of NO.

Endothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED.All men were evaluated for ED and divided into two groups: 80 patients suffering from ED for 1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated.The mean age of patients in ED group was 60.4 ± 11.3 years and 55.4 ± 9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5 ± 38.3 and 132.5 ± 53.3 ng/ mL, respectively, P 0.001). The IGF-1 levels were positively correlated with ED score (r = 0.623, P 0.01).In this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population.La dysfonction endothéliale et les altérations vasculaires jouent un rôle crucial dans la pathogenèse de la dysfonction érectile (DE). L’Insulin-like Growth Factor-1 (IGF-1) est l’un des facteurs de croissance qui ont un vaste champ d’effets biologiques. IGF-1 est un médiateur important de la croissance, différentiation et transformation cellulaires dans différents tissus. Le but de la présente étude était de rechercher une association entre les taux d’IGF-1 et la dysfonction érectile.La dysfonction érectile a été évaluée chez tous les hommes, constitués en 2 groupes : 80 patients souffrant de DE depuis plus d’un an, et 80 sujets sans DE recrutés comme groupe témoin dans l’étude. Le diagnostic de DE était basé sur le score 5 de l’Index International de la Fonction Erectile. Les taux d’IGF-1 ont été mesurés par immunodosage automatisé par chemiluminescence. La relation entre les taux d’IGF-1 et le score de la DE a été statistiquement évaluée.L’âge moyen des patients du groupe DE était de 60.4±11.3 ans et de 55.4±9.6 dans le groupe témoin. Les taux plasmatiques d’IGF-1 étaient significativement plus bas dans le groupe DE que chez les témoins (respectivement 96.5±38.3 et 132.5±53.3 ng/mL, P0.001). Les taux d’IGF-1 étaient positivement corrélés au score de la DE (r = 0.623, P0.01).Nos résultats indiquent que les taux sériques d’IGF-1 sont associés à une dysfonction endothéliale qui prédit la DE. L’IGF-1 sérique apparaît être un prédicteur spécifique de la DE, et il pourrait être utilisé pour une prédiction précoce de la DE dans la population masculine.

Introduction/Objective: Ureteral obstruction is a common pathology and causes kidney fibrosis and dysfunction at late period. In this present study, we investigated the antifibrotic and antiinflammatory effects of hydrogen sulfide on kidney damage after unilateral ureteral obstruction (UUO) in rats. Materials and Methods: 24 rats were divided into four groups. Group 1 was control, group 2 was sham, group 3 included rats with UUO and group 4 rats with UUO which were given sodium hydrogen sulfide (NaHS)-exogenous donor of hydrogen sulfide (intraperitoneally 56μmoL/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis were determined histopathologically in a part of the kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of the kidneys. Urea-creatinine levels were investigated by blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results: There was no significantly difference for urea-creatinine levels among groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing of tubular necrosis and fibrosis in group 4 (p

Background The pathogenesis of psoriasis has not been known exactly yet. Recently, it has been suggested that increased reactive oxygen species (ROS) such as nitric oxide (NO) and malondialdehyde (MDA) may play a part in the pathogenesis of various skin diseases, including psoriasis. Objectives In this study, we aimed to investigate the role of ROS in the pathogenesis of psoriasis. Methods A convenience sample of 23 patients with psoriasis and 23 healthy subjects consented to participate in the study. Plasma NO and MDA levels were measured in all participants. Psoriasis area and severity index (PASI) and tissue levels of MDA on lesional and non-lesional skin regions of psoriasis patients were measured. In addition, the correlation between age, gender with plasma NO, plasma MDA and tissue MDA was assessed. Results Plasma levels of NO and MDA in psoriasis patients (135.8 lmol ⁄ L, 4.33 lmol ⁄ L, respectively) were statistically significantly higher than those in controls (33.6 lmol ⁄ L, 2.03 lmol ⁄ L, respectively). Tissue levels of MDA in lesional tissues (49.18 nmol ⁄ gr) were significantly higher than those in non-lesional tissues (28.41 nmol ⁄ gr). A significant correlation was not found between the PASI and levels of NO and MDA. In addition, a significant negative correlation was found between the plasma NO levels and age. Conclusion NO and MDA levels are elevated in psoriasis patients, which may indicate that oxidative stress plays an important role in the aetiopathogenesis of psoriasis.

Doxorubicin (DOX) has been used in the treatment of childhood cancers, but its usage is limited because of cardiotoxicity. There are many studies on the role of nitric oxide (NO) in several cardiac diseases. However, to the authors’ knowledge, no studies have investigated the plasma levels of total nitrite, a stable product of NO, in children that received DOX. The authors determined plasma total nitrite levels in 29 children who received DOX and investigated the correlations between these and other clinical and laboratory findings. All patients were in remission during the study period. Plasma total nitrite levels and cardiac functions were determined prospectively. The mean cumulative DOX dose was 310.0 ± 90.9 mg/m 2 . In echocardiographic evaluation, 3 patients (10.3%) had a pathological value for ejection fraction (EF) and/or fractional shortening (FS), whereas 11 patients (37.9%) had a threshold value. Total nitrite levels were higher in patients than in matched controls (75.24 ± 39.4 vs 43.14 ± 10.58 µmol/L, respectively, P < .001). It was also found to be higher in patients who had a pathological/threshold value of EF and FS than in patients who had a physiological value of EF and FS (92.35 ± 50.36 vs 59.26 ± 13.56 µmol/L, respectively, P = .038). A negative correlation was found between FS and plasma total nitrite level (r =− .42, P = .023). The authors speculate that increased NO may be a sign of subclinical cardiotoxicity of DOX.

Summary The aim of this study was to investigate p38-mitogene-activated protein kinase (p38-MAPK), nuclear factor-kappa B (p65-NF-kB) and inducible nitric oxide synthase (iNOS) expression in an experimental model of varicocele in the rat testis. Male Wistar albino rats (n = 18) were divided into three equal groups: control group, sham operated group and left varicocele-induced group. Malondialdehyde (MDA), nitric oxide (NO) and reduced glutathione (GSH) levels were biochemically assessed, and the p38-MAPK and NF-kB activity, and iNOS expression were immunohistochemically studied in the right and left testicles of rats from each group. The GSH levels were significantly decreased, whereas the level of MDA and NO was significantly increased in the testicular tissues of rats in varicocele group compared with those of the control and sham groups. There was a marked staining for iNOS, p38-MAPK and p65-NF-kB expression in rats of varicocele group compared with the sham group. There was no positive staining in rats of control group. There were significant differences in biochemical, histological and immunohistochemical studies, but no significant differences were noted between other groups. p38-MAPK and p65-NF-kB activation, and iNOS expression have a significant role in varicocele-induced testicular dysfunction.

Summary Background The hepatitis B virus (HBV) polymerase gene completely overlaps with the envelope gene. In the present study we aimed to monitor the prevalence and pattern of the typical mutations for hepatitis B surface antigen (HBsAg) escape, and concomitantly nucleos(t)ide analog (NUC) resistance mutations, in Turkish patients undergoing different antiviral therapies and in treatment-naive patients with chronic hepatitis B (CHB). Methods The investigation was undertaken between March 2007 and August 2009 and involved a total of 142 patients under NUC therapy (88 males; mean age 42 years (range 13–68); hepatitis B e antigen (HBeAg) negativity in 94 patients; HBV DNA median log 4.3 log 10 IU/ml (range 2.0–>6.0); alanine aminotransferase (ALT) median level 76.1 IU/ml (range 12–1082)) and 185 treatment-naive CHB patients (120 males; mean age 39 years (range 1–76 years); HBeAg negativity in 132 patients; HBV DNA median log 3.5 log 10 IU/ml (range 2.0–6.0); ALT median level 60.7 IU/l (range 8–874)). Results The overall prevalence of typical HBsAg escape mutations found in the CHB patients was 8.3% (27/327). In the NUC therapy group the prevalence was 8.5% (12/142), with the following patterns: sY100C+sI110V, sL109I, sP120T, sP127T, sG130R+sG145X, sS132A+sY134N, sY134N+sG145R, sC137G, sD144E, sG145R. In the treatment-naive group the prevalence was 8.1% (15/185), with the following patterns: sL109I, sI110V, sS117INST, sP120T, sP127T, sM133I, sC137L+sG145R, sS143L. However, NUC resistance mutations were found in 7.7% (11/142) of the patients on NUC therapy and 3.8% (7/185) of the treatment-naive group patients. Interestingly, the treatment-naive patients had preexisting drug resistance mutations related to lamivudine (rtL180M+rtM204I), adefovir (rtA181V, rtQ215S, rtI233V), entecavir (intermediate susceptibility with rtL180M+rtM204IHBV variant), telbivudine (rtL180M+rtM204I), and tenofovir (rtA194T). Conclusions The findings of this study show preexisting typical HBsAg escape and NUC resistance mutations are possible. The genetic arrangement of the HBV genome with polymerase and surface genes overlapping has substantial public health and diagnostic implications and relevance.

Objective. The aim of the study was to investigate the role of malondialdehyde, nitric oxide and adrenomedullin in the etiopathogenesis of preeclampsia. Material and Methods. Forty-two pregnant women with preeclampsia and 30 healthy pregnant women were involved. The plasma concentrations of malondialdehyde, nitric oxide, and adrenomedullin were compared between the study group and the control group. Results. In women with preeclampsia the plasma concentrations of malondialdehyde was higher while nitric oxide and adrenomedullin concentrations were lower compared to control subjects. Conclusion. We concluded that the plasma levels of ADM and NO are decreased while MDA levels are increased in subjects with preeclampsia and that might contribute to the pathophysiology of preeclampsia through the lack of a paracrine vasodilatory effect on uteroplacental blood flow.

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe gram-negative infections. Reactive oxygen spaces (ROS) are important mediators of gentamicin-induced nephrotoxicity. Peroxisome proliferator-activated receptors (PPARs) have different activities including antioxidant properties. This study was performed to investigate the protective role of PPAR-γ agonist against GEN-induced nephrotoxicity. Male Wistar Albino rats were randomly divided into the following four groups, each of which consisted of six animals: (1) control; (2) intraperitoneally injected with GEN for 14 consecutive days (100 mg/kg/day); (3) treatment with rosiglitazone (RSG) via nasogastric gavage (10 mg/kg/daily for 14 days); (4) treatment with GEN + RSG combination for 14 day. Rats were decapitated on the 15th day and kidneys were removed. Urine was collected for every 24 h for the determination of daily urine volume. Urea, creatinine, Na(+) and K(+) levels were measured in blood. Malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) levels along with glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activities were determined in the renal tissue. Changes in body weight were recorded. GEN treatment was found to cause nephrotoxicity as evidenced by elevation of serum urea and creatinine levels. Renal impairment was also assessed by the renal histology. The significant decrease in GSH and increases in MDA and NO levels as well as a decrease in GSH-Px, CAT, and SOD activities indicated that GEN-induced renal damage was mediated through oxidative reactions. On the other hand, RSG administration protected kidney tissue against GEN-induced and free radical-mediated oxidative renal damage in rats.

To investigate whether melatonin (MLT) treatment has any protective effect on unilateral ureteral obstruction (UUO)-induced kidney injury in rats.Six animals were included in each of the following five groups: group 1, sham operation but no treatment; group 2, unilateral ureteral ligation but no treatment; group 3, sham operation + MLT; group 4, unilateral ureteral ligation + MLT; group 5, unilateral ureteral ligation +5% ethanol (the vehicle of MLT). The injected dose of MLT was 1 mg/kg/day (intraperitoneal). MLT and vehicle were injected daily, beginning 5 days before the unilateral ureteral ligation or sham operation and until 10 days after it. At 10 days after UUO, all rats were sacrificed with high-dose ketamine. Malondialdehyde, glutathione, nitric oxide (NO), and 8-hydroxydeoxyguanosine levels and inducible NO synthase (iNOS), p38-mitogen-activated protein kinase (p38-MAPK), and nuclear factor kappa B (NF-kB) expression were studied. Histopathological examination of the obstructed kidney was also performed.UUO was accompanied by a significant increase in malondialdehyde, NO, and 8-hydroxydeoxyguanosine along with a significant decrease in glutathione levels in the kidney tissue, as well as a significant elevation in iNOS, p38-MAPK, and NF-kB expression. MLT treatment resulted in reduction of the parameters of oxidative stress and the iNOS, p38-MAPK, and NF-kB expression. MLT treatment also reduced the development of leukocyte infiltration and interstitial fibrosis in UUO rats.MLT may prevent UUO-induced kidney damage in rats by reducing oxidative stress. The mechanism for this is likely mediated via reduction in the expression of iNOS, p38-MAPK, and NF-kB, since MLT reduces the activation of these pathways.

BACKGROUND: The aim of this study was to investigate the cellular/biochemical mechanisms by which cisplatin (CIS) causes testicular toxicity. We evaluated the role of inducible nitric oxide synthase (iNOS) expression, mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kB) activation in the pathogenesis of testicular damage induced by CIS, and investigated the effects of curcumin (CMN) against CIS-induced testicular injury in rats. METHODS: Rats were divided into five equal groups: (I) control, (2) CIS, (3) CMN, (4) CIS + CMN and (5) CIS + corn oil. After the treatment, body and testicular weights, and plasma testosterone levels were observed, along with the biochemical, histopathological and immunohistochemical changes in testes. RESULTS: Testicular weight, plasma testosterone levels, activities of glutathione peroxidase (GSH-Px) and glutathione (GSH) levels signifi- cantly decreased, whereas the level of malondialdehyde (MDA) and nitric oxide (NO) significantly increased with CIS compared with the controls. A significant increase in plasma testosterone levels, GSH levels and GSH-Px activity, and a decrease in MDA and NO levels in tes- ticular tissue were observed with CIS + CMN compared with that with CIS alone. There was marked staining for iNOS, MAPK/p38 and NF-kB/p65 expression with CIS compared with the control and CIS + CMN groups. CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant maturation arrest and perivascular fibrosis. CMN administration to CIS-treated rats significantly prevented these histopathologic changes. CONCLUSIONS: MAPK and NF-kB activation have a significant role in CIS-induced testicular toxicity. CMN has a strong potential for use as a therapeutic adjuvant in CIS gonadotoxicity.

To evaluate the role of the inducible nitric oxide synthase (iNOS), selective nuclear factor-kB (NF-kB), and p38-mitogene-activated protein kinase (p38-MAPK) on hyperoxaluria-induced oxidative stress and stone formation in rat kidneys. The rats were divided into five groups: group 1, control group; group 2: ethylene glycol (EG) group; group 3: EG + pomegranate juice (PJ)-low group; group 4: EG + PJ-middle group; group 5: EG + PJ-high group. Rats were sacrificed on 7, 15, and 45 days. The iNOS expression, p65-NF-kB and p38-MAPK activity, and oxidative stress markers were evaluated in the kidney. Crystal depositions were evident on day 7, and mild and severe crystallization were observed on day 15 and 45 in EG group, respectively. There was limited or no crystal formation in rats in both middle- and high-dose PJ groups when compared to low-dose PJ group. Crystal depositions, iNOS, p38-MAPK and p65-NF-kB activity, and oxidative stress markers were found to be decreased by middle- and high-dose PJ treatment. PJ was found to have inhibitory effects on renal tubular cell injury and oxidative stress caused by oxalate crystals by reducing ROS, iNOS, p38-MAPK, and NF-kB expression.

We aimed to study the protective effects of pomegranate juice (PJ) on ethylene glycol (EG)-induced crystal deposition in renal tubules, renal toxicity, and inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB activities in rat kidneys.Fifty-six rats were divided into four equal groups: Control, EG, EG + 50 microL PJ/d (PJ50), and EG + 100 microL PJ/d (PJ100). Rats were sacrified on days 10 and 45. Tissue sections were evaluated under light and polarized microscopy for the presence and degree of crystal deposition and toxicity in the kidneys. Crude extracts of the cortex were used to determine reduced gluthatione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels.In the EG group, crystal depositions were more evident and mild crystalization was observed in proximal tubules on day 10; severe crystalization and granulovacuolar epithelial cell degeneration were observed on day 45. There was limited or no crystal formation in the EG + PJ-given groups. There were completely normal renal and tubular structures in the control group. There was no significant difference between the four groups in serum levels of sodium, potassium, blood urea nitrogen, and creatinine in any sampling time. Hyperoxaluria, a marked increase in MDA and NO levels, and decrease of GSH were observed in the EG-given groups compared with the others. There were marked iNOS and p65 expressions in only the EG-given rats compared with control and PJ groups, immunohistochemically.This experiment shows the protective effect of PJ in the EG-induced crystal depositions in renal tubules.

The management of epidural hematoma is classified into surgical or conservative treatment according to clinical and radiologic parameters. In the recent years, the number of paper suggesting conservative management has been increasing. The experimental works that have been performed are based on especially the effects of epidural hematomas. Basic pathophysiologic factors on ischemia result of brain trauma are based on biochemical mediators. Nitric oxide (NO) and malondialdehyde (MDA) are the substances that play important roles in brain damage after trauma.In this study, 36 rats are divided into three groups (n = 12/group). Epidural hematoma was achieved by 0.1 ml autolog blood in rat epidural space with balloon model. Early and late phase biochemical effects on parenchyma of epidural hematoma operated in a volume which neither alters intracranial pressure (ICP) nor creates shift effect were observed. Biochemical changes of NO and MDA levels were examined in each of three experimental groups.NO values increased significantly in the early group (6 hours) compared with those in the control group. Difference of NO values between the control and late groups was not significant. An increase has been found in MDA values in the control group compared with those in the early group. MDA values of the late group (30 days) were closer to that of the control group.In this study, considering biochemical results, we have found that conservative volumes which neither increase ICP nor cause brain shift do not lead to permanent changes on brain.

This study evaluated the influence of three different delivery methods (vaginal delivery, caesarean section under general anaesthesia and caesarean section with spinal block) on maternal and neonatal blood levels of nitric oxide and malondialdehyde. Results showed that caesarean section with spinal anaesthesia causes less oxidative stress compared to vaginal delivery with epidural analgesia and elective caesarean section with general anaesthesia.

To study the protective effects of a selective nuclear factor kappa B (NF-kappaB) inhibitor, pyrolidium dithiocarbamate (PDTC), on ethylene glycol-induced crystal deposition in the renal tubules, renal toxicity, as well as inducible nitric oxide synthase (iNOS) and NF-kappaB activities in rat kidneys.Rats were divided into three equal groups: control, ethylene glycol-treated (EG), and ethylene glycol + PDTC treated (EG+PDTC). Rats were sacrificed on day 7, 15, or 45, and tissue sections were evaluated under light and transmission electron microscopy for the presence and degree of crystal deposition and toxicity in the kidneys. The iNOS and NF-kappaB activity were evaluated immunohistochemically, with p65 being stained to define NF-kappaB activity. Crude extracts of the cortex were used to determine reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) concentrations.Crystal depositions were more evident in the proximal tubules on day 7 in the EG than in the other groups. Mild crystallization was observed on day 15, and severe crystallization and granulovacuolar epithelial-cell degeneration were observed on day 45. There was limited or no crystal formation in the EG+PDTC group and completely normal renal and tubular structures in the control group. Whereas ethylene glycol administration stimulated iNOS and NF-kappaB/p65 activity in renal tubules, PDTC inhibited it. Rats given only vehicle demonstrated no significant alterations. Hyperoxaluria, a marked increase in MDA and NO concentrations, and a decrease in GSH were observed in the EG group.This experiment has shown the role of transcription factors, NF-kappaB, and iNOS in ethylene glycol-induced crystal depositions in renal tubules.

Background: Translocating enteric bacteria play an important role in the development of infections following partial hepatectomy. The intestine itself is the first line of defence against bacterial translocation (BT). We investigated the effect of N-acetylcysteine (NAC) on BT and the intestinal wall. Methods: We compared four groups of Sprague–Dawley male rats (eight in each group): sham, sham plus preoperative single dose of NAC, partial hepatectomy and partial hepatectomy plus preoperative single dose of NAC. Microorganism count in the tissues and the glutathione and malondialdehyte contents of the intestinal wall were studied at the end of the 24th hour. Results: Bacterial growth was observed in the spleen and mesenteric lymph nodes in the sham group. There was bacterial growth in all the samples of the partial hepatectomy group. Differences were significant except in atrial and portal blood counts. In the partial hepatectomy plus NAC treatment group, counts were significantly low in all, except atrial and portal blood samples. The malondialdehyte level in the intestinal wall was 35.38 – 10.27 in the sham group, increasing significantly in the partial hepatectomy group (69.50 – 21.48), and decreasing in the partial hepatectomy plus NAC treatment group (35.63 – 14.12). Glutathione levels decreased significantly in the partial hepatectomy group and increased with preoperative single-dose NAC. Conclusion: Partial hepatectomy resulted in oxidative disturbances in intestinal wall, which in turn gave rise to BT. Parenteral NAC protects the intestinal wall from oxidative injury and attenuates BT.

We evaluated changes in urinary nerve growth factor (NGF) and NGF/creatinine (NGF/Cr) levels after increasing the dosage of solifenacin in overactive bladder patients. The study groups included 59 overactive bladder (OAB) patients and 20 healthy subjects as controls. We measured NGF at baseline for the patients and controls, and used the Overactive Bladder Awareness Tool (OAB-V8) to evaluate urinary symptoms. All patients received a treatment of solifenacin 5 mg for 6 weeks. The responders to treatment served as group 1 and nonresponders received solifenacin 10 mg for an additional 6 weeks. Responders and nonresponders to the 10-mg treatment were defined as groups 2 and 3 respectively. NGF was measured after each treatment using the ELISA method and normalized by the urinary creatinine levels (NGF/Cr). There were 21, 22 and 16 patients in groups 1, 2, and 3 respectively. At baseline, the NGF and NGF/Cr levels were higher in groups 1, 2, and 3 compared with the controls. After the solifenacin 5 mg treatment, the NGF and NGF/Cr levels of group 1 individuals decreased to those of the control level. After increasing the dosage of solifenacin to 10 mg in group 2, the NGF and NGF/Cr levels decreased to normal levels. In group 3 (patients who did not responded to any treatment), these levels remained unchanged. Our results suggest that urinary NGF could be a potential biomarker for monitoring the treatment of symptoms in OAB patients who are treated with solifenacin.

Colorectal cancers are the most common cancers of the gastrointestinal system. A significant relationship was detected between the metastasis and tumor angiogenesis of colorectal cancer. The aim of the present study was to investigate the association between some cytokines and tumor stages. Additionally, association between VEGF gene polymorphisms and colorectal cancer was studied.In this study, we measured serum IL-18, IL-2, VEGF, endothelin (ET), and nitric oxide (NO) levels in 44 patients with colorectal cancer and 44 healthy controls. Also we investigated VEGF G634C (rs2010963) and VEGF C936T (rs3025039) polymorphisms of VEGF gene in these groups by using a PCR-RFLP method. Data were analyzed statistically.Serum levels of IL-18, VEGF, IL-2 and NO were significantly higher in patients with colorectal cancer when compared to controls (p0,05). Serum ET levels were found to be similar in colorectal cancer patients and healthy controls. When we compared the two subgroups constituted by tumor stages (Stage 1-2 and Stage 3-4) with each other, serum VEGF levels were found significantly higher in stage 3-4 group than stage 1-2 group (p0,05). No significant difference was found between subgroups with regard to other parameters. We found that investigated VEGF G634C and VEGF C936T polymorphisms were not associated with the severity of colorectal cancer. (P=0.228 for VEGF G–634-C; P= 0.484 for VEGF C–936-T) CONCLUSION: In the future, serum levels of IL-18, VEGF, IL-2 and NO may be a useful marker for diagnosis of patients with colorectal cancer. Additionally we consider that serum VEGF levels can be used as a tumor marker to predict prognosis of cancer. However, larger studies with long-term follow-up are necessary to clarify this hypothesis. On the other hand, there is necessity for the new studies for determination of association between VEGF gene polymorphism and colorectal cancer.

Oxidative stress caused by smoking has been implicated in many pulmonary diseases. Smoking causes reductions in plasma nitrate plus nitrite (NOx) concentrations and increases in plasma malondialdehyde (MDA) concentrations, which indicate oxidative stress and lipid peroxidation, respectively. In this study, we investigated the acute effects of smoking a single cigarette on the plasma concentrations of NOx and thiobarbituric acid reactive substances (TBARS) including MDA, and whether administration of erdosteine, a mucolytic and antioxidant agent, affects these parameters.Thirty healthy smokers were included in the study. Subjects smoked a single cigarette in 10 minutes on the study day. For analysis of NOx, TBARS and cotinine, blood was drawn from each subject before and 5 and 30 minutes after smoking. The subjects were then randomly divided into two groups, one receiving placebo and the other erdosteine suspension 175mg/5mL twice daily for 1 month. After this treatment period, the same study protocol was carried out. Two subjects in the placebo and five subjects in the study group were excluded because of noncompliance.Twenty-three (14 female, 9 male) subjects completed the study. Their mean age was 32 +/- 8 years and their smoking history was 14 +/- 9 pack-years. Baseline NOx, TBARS and cotinine concentrations were similar between the groups. NOx concentrations decreased significantly after smoke exposure. At the end of the treatment period there were no significant differences in NOx, TBARS or cotinine concentrations between the groups. The concentration of TBARS after smoking decreased significantly in the erdosteine-treated group (at 5 minutes: 2.8 +/- 0.5 micromol/L before treatment and 2.3 +/- 0.3 micromol/L after treatment, p0.05; at 30 minutes: 2.8 +/- 0.5 micromol/L before treatment and 1.8 +/- 0.7 micromol/L after treatment, p0.05). Smoking history was significantly correlated with cotinine concentrations.Acute smoke exposure decreased plasma NOx concentrations in healthy smokers, and this was not changed with erdosteine treatment. However, significant decreases were noted in TBARS concentrations after smoke exposure in the group that received erdosteine, suggesting that short-term erdosteine administration might help prevent smoking-induced lipid peroxidation.

The tubers of Bongardia chrysogonum, which are used in the folk medicine in the form of 2–3% decoction in the province of Gaziantep, are supposed to treat urinary track, prosthate disorders, and hemorrhoid. The objective of this study was to assess the effect of these tubers on some serum parameters and spleen, liver, and kidney tissues in rats. One, two, and three percent decoctions of the B. chrysogonum were prepared, and instilled into the stomach of the rats, 0.2 ml/day, for 60 days via an orogastric tube. The serum glucose, creatinine, urea, uric acid, total cholesterol, triglycerides, total protein, albumin, globulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), lactate dehydrogenase (LDH), sodium (Na), potassium (K), calcium (Ca), chloride (Cl), phosphorus (P), and magnesium (Mg) levels were measured in the blood obtained via intracardiac catheterization on 15th, 30th, 45th, and 60th days, respectively. Overall health st...

Summary Surgical stress may cause neural, endocrine, metabolic and humoral responses depending on the severity of the procedure. In this study, we aimed to study the effect of the preoperatively given ascorbic acid (AA), which is an anti-oxidant, and its role in the biosynthesis of neuropituitary hormones on the surgical stress response. Twenty-two American Society of Anaesthesiologists I and II patients ageing between 18 and 40, who have no endocrine and metabolic disease, and undergoing abdominal operation for non-malignant diseases were allocated to the study. These non-premedicated patients were divided into two groups in random: Group I, etomidate group; and Group II, AA plus etomidate group. AA was given to patients in Group II 20 min before etomidate injection. After monitoring the patient, anaesthetic induction was applied by giving 0.3 mg/kg of etomidate, 2 µg/kg of fentanyl and 0.1 mg/kg of vecuronium. Anaesthesia was continued with 1–0.7% isoflurane and N2O/O2 (67 and 37%, respectively). Tramadol was given for the management of post-operative analgesia. Blood samples were obtained from all patients before the operation and at second, sixth, twelfth and twenty-forth hours after the beginning of operation for cortisol, adrenocorticotropic hormone (ACTH), osteocalcin, insulin and blood glucose level analyses. There was no statistically significant difference in cortisol, osteocalcin, insulin and glucose levels in both groups, when compared to the control levels. Whereas, patients in Group II had higher levels of cortisol than the control group at sixth hour, which were in normal limits, and there was no decrease in osteocalcin concentration. ACTH level was increased at the second and sixth hours, which was statistically significant, but at twelfth and twenty-forth hours, they were close to control group levels. As a result, we conclude that AA given before anaesthesia achieved by etomidate is not sufficient for the prevention of surgical stress response and that AA induction before anaesthesia should be preferred, particularly for the prevention of decrease in osteocalcin levels.

Objectives: Aim of this study was to evaluate implication of pregnancy induced hypertension on maternal plasma lipid, lipoprotein, apolipoprotein concentrations and lipid peroxidation products by a comparison of normal pregnancy vs. preeclampsia. Design and methods: Thirty-four women with preeclampsia and 32 healthy pregnant women (controls) in the third trimester were recruited for this study. Results: In the preeclamptic group plasma total triglyceride, low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA) and apolipoprotein B (apo-B) were significantly increased, while plasma high density lipoprotein cholesterol (HDL-C) was significantly decreased compared to that of control group. There was no significant difference in total cholesterol and apolipoprotein A1 (apo-A1) concentrations. Conclusion: Our findings suggest that preeclampsia share some metabolic characteristics with coronary artery disease such as dislipidemia and increased lipid peroxidation. However lipoprotein concentrations may be better biochemical markers of dislipidemia in the preeclamptic state than the corresponding apolipoproteins. © 2003 The Canadian Society of Clinical Chemists. All rights reserved.

Nitric 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 &PLUSMN; 9.8 and 21.7 &PLUSMN; 7.3 μmol/ 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.

Dilated 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; p0.001). 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 (P0.05) and 1.98 +/- 1.24 vs 2.75 +/- 1.68 (p0.05), 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.

Detrusor instability (DI) and detrusor-external sphincter dyssynergia lead to poor bladder emptying and high bladder pressure. Recent results indicate that nitric oxide (NO) is an important transmitter or messenger molecule in autonomic neurotransmission. Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide, originally purified from human pheochromocytoma. Since NO and AM have vasodilatory effects on smooth muscles, we considered them to be of interest in children with DI. We determined the tissue levels of NO and AM in 14 children with DI, and compared these with 6 children with normal bladder activity. Bladder biopsy total nitrite levels (nmol/g tissue) were decreased in children with DI (10.69+/-0.91 vs. 12.83+/-0.98, P0.01). However, AM levels (pmol/g tissue) were increased in the same patients (48.84+/-3.52 vs. 28.79+/-1.53, P0.001). According to our results, decreased NO production probably has a role in the pathophysiology of DI, although increased AM appears to be compensatory. NO may provide a therapeutic target in clinical situations related to DI. However, the functional significance of AM and NO in bladder smooth muscle remains to be determined by further detailed studies.

Background 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 Obgene, 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 (m2)) 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 χ2 test was used for statistics as indicated, and P

Background: Nitric oxide (NO), hydroxyl radical (OH.), superoxide anion (O2 −) and hydrogen peroxide (H2O2) are free-radicals released in oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT) are antioxidant enzymes, mediating defense against oxidative stress. Excess NO and/or defective antioxidants cause lipid peroxidation, cellular dysfunction and death. Age-related maculopathy (ARM) or degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. The etiology is unclear and the molecular factors contributing this disease remain to be specified. Aims: This multicenter, double-blind, cross-sectional study aimed to investigate plasma NO and lipid peroxidation levels with relation to antioxidant enzyme activities in erythrocyte and plasma of patients with ARMD compared with healthy control subjects. Methods: NO, lipid peroxidation (measured as plasma malondialdehyde [MDA] levels) and the catalytic activity of SOD, GSHPx and CAT were measured in a group of 41 patients with maculopathy (19 men, 22 women; 67.12 ± 3.70 years) and compared with 25 age- and sex-matched healthy control subjects without maculopathy (12 men, 13 women; 68.04 ± 3.02 years). NO and MDA levels were measured in plasma, CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Color fundus photographs were used to assess the presence of maculopathy, and the patients were divided into two groups using clinical examination and grading of photographs; early-ARM (n = 22) and late-ARMD (n = 19). Results: All patients with maculopathy had significantly (p

AIM: Behçet's disease (BD) is an inflammatory vasculitis with immunologic, endothelial and neutrophil alterations. Adenosine deaminase (AD) is a marker of T-cell activation and is related to the production of reactive oxygen species by neutrophils with the production of NO(*), O(2)(*-), H(2)O(2) and OH(*). We reported increased tumour necrosis factor-alpha, soluble interleukin-2 receptor, interleukin-6, interleukin-8 and NO(*) in active BD. As there is a relation between cytokines, T cells and oxidative stress in inflammatory diseases, this study further evaluated: (1) plasma AD activity and its correlation with acute phase reactants; (2) thiobarbituric acid-reactive substances (TBARS) as an indicator for lipid peroxidation; and (3) antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase in patients with BD. The effect of disease activity and correlations between the measured parameters were explored. METHODS: A total of 35 active (n=17) or inactive (n=18) patients with BD (16 men, 19 women) satisfying International Study Group criteria, and 20 age-matched and sex-matched controls (nine men, 11 women) were included in this cross-sectional case-control study. AD and TBARS were measured in plasma, catalase in red blood cells (RBC), and SOD and GSHPx in both plasma and RBC in both groups. Acute phase reactants (alpha(1)-antitrypsin, alpha(2)-macroglobulin, neutrophils, erythrocyte sedimentation rate) were used to classify patients as active or inactive. RESULTS: Plasma AD (mean+/-standard error of the mean, 36.1+/-0.7 U/l) and TBARS (4.2+/-0.1 nmol/ml) levels were significantly (for each, p

PURPOSE Pro-inflammatory cytokines are produced by tissues and play a vital role in the host inflammatory response and uveitis. Nitric oxide (NO) can be produced in large amounts as a response to experimentally-induced uveitis or cytokines. In this study, we measured the levels of pro-inflammatory cytokines such as interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha and free-radical in aqueous humor after Nd:YAG laser iridotomy in rabbits, and investigated whether timolol maleate an anti-glaucoma drug, or a NO synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME) had an inhibitory effect on these molecules, since L-NAME is a known anti-inflammatory agent in rabbits. METHODS Bilateral experimental Nd:YAG laser iridotomy (power 7.5 mJ, mode single burst, aiming beam 4) was performed on 18 rabbits under general plus topical anesthesia. Aqueous humor samples were taken by clear corneal paracentesis preoperatively, and 1 and 24 h postoperatively. Six rabbits (12 eyes) were given bilateral topical timolol maleate 0.5% (Timoptic) drop b.i.d. (group 1), six rabbits (12 eyes) received bilateral 0.1 ml subconjuntival injections of L-NAME (150 mg/kg) (group 2), and six rabbits (12 eyes) were treated with topical balanced salt solution (BSS) b.i.d. (control). RESULTS. Preoperative cytokine and NO levels were comparable in the three groups, with no significant differences. In addition, there was no significant difference in baseline cytokine levels between the right and left eyes. In all groups, pre- and postoperative mean IL-1beta levels were below the detection limit of the assay (