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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.

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.

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

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.

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.

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.

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.

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

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 (

AIM: Behçet's disease (BD) is asystemic 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 micromol/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-alpha (7.9+/-0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3+/-0.5 micromol/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 micromol/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-alpha indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-alpha 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.

Background: It is well known that mucosal changes and alterations in liver function occur in the experimental obstructive jaundice model. Aims: We aimed to evaluate the effect of resveratrol on obstructive jaundice-induced changes in the small bowel mucosa and liver using ischaemia-modified albumin as a marker of oxidative damage. Study Design: Animal experimentation. Methods: The study used a rodent experimental model of obstructive jaundice, including a sham group (1), a control group (2), and a study group (3). Wistar albino rats were used. Jaundice was produced by ligation of the bile duct in Groups 2 and 3. In Group 3, resveratrol was administered intraperitoneally for 14 days. Results: In terms of the structure and the size of the mucosal villi, significant thickening and blunting were detected in Group 2 compared with Group 1. These changes were significantly less noticeable in Group 3 compared with Group 2. Levels of ischaemia-modified albumin were significantly higher in Group 2 compared with those in Group 1, and they were significantly decreased in Group 3 compared with Group 2. Conclusion: Resveratrol administration to obstructive jaundiced rats reduced the organic effects of obstructive jaundice on small bowel mucosa and liver oxidative stress. We believe that this reduction might attenuate bacterial translocation and systemic effects of secreted cytokines. (Balkan Med J 2014;31:95-99).

AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats. METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group. Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally 3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other 16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells (RGCs) have been marked with dextran tetramethylrhodamine (DTMR) retrograde at the end of the sixth week and after 48h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the whole-mount retina. Whole-mount retinal tissues homogenized and nitric oxide (NO), malondialdehyde (MDA) and total antioxidant capacity (TAC) values were measured biochemically. RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group (Bonferroni, P

Cisplatin is a chemotherapeutic agent which affects renal functions adversely. The best indicator of renal functions is glomerular filtration rate (GFR) measurement. Cystatin-C appears to be a good alternative to existing methods of measuring GFR. However, it is controversial whether Cystatin-C demonstrates GFR correctly for patients receiving chemotherapy. This study aimed to investigate the correlation between GFR values calculated by Cystatin-C based formulas, radionuclidic method (multiple blood sampling) and blood Cystatin-C values in patients with lung cancer, receiving cisplatin treatment in both pre-treatment and post-treatment periods.Thirty-six patients with lung cancer who were going to receive cisplatin treatment were included in this study. However, the evaluation was performed with 20 patients since 16 of them could not complete the treatment. Blood Cystatin-C values, GFR values calculated via Cystatin-C based formulas, and radionuclidic method were investigated before and after the cisplatin treatment.After treatment significant decreases were detected in GFR values, obtained via radionuclidic measuring method. However, there was no significant difference in Cystatin-C values between pre-treatment and post-treatment periods. Also GFR values obtained by Cystatin-C based formulas were not significantly different in pre-treatment and post-treatment periods. There were meaningful correlations between radionuclidic method and Cystatin-C values and Cystatin-C based formulas before treatment. However, all correlations disappeared after the treatment.GFR values, calculated by Cystatin-C may not be reliable in following renal functions in patients receiving chemotherapy. When reliable monitoring of the renal functions is necessary radionuclidic method may be preferred in these patients.

WOS: 000370436100006 PubMed ID: 25838069 Aims: Ureteral obstruction may cause permanent kidney damage at late period. We know that the pomegranate extract (PE) play a strong role on removal of free oxygen radicals and prevention of oxidative stress. In the current study study, we evaluated the effect of PE on kidney damage after unilateral ureteral obstruction (UUO). Settings and Design: A total of 32 rats were divided into four groups. Group 1 was a control, Group 2 was a sham, Group 3 was rats with UUO and Group 4 was rats with UUO that were given PE (oral 100 L/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Subjects and Methods: Tubular necrosis, mononuclear cell infiltration, 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 Analysis Used: Statistical analyses were performed by the Chi-square test and one-way analysis of variance. Results: There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis, mononuclear cell infiltration and fibrosis in Group 3, and there was significantly decreasing for tubular necrosis, mononuclear cell infiltration and fibrosis in Group 4 (P < 0.005). Furthermore, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in Group 3 compared the other groups (P < 0.005). Conclusions: We think that the PE prevents kidney damage by decreasing oxidative stress in kidney.

WOS: 000354634500014 PubMed ID: 26005969 Introduction: Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO) in rats. Materials and Methods: 32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/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 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. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results: There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p

WOS: 000346477700001 PubMed ID: 25518026 OBJECTIVES: Serotonin plays a central role in ejaculation and selective serotonin reuptake inhibitors have been successfully used to treat premature ejaculation. Here, we evaluated the relationship between a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the response of patients with premature ejaculation to SSRI medication. METHODS: Sixty-nine premature ejaculation patients were treated with 20 mg/d paroxetine for three months. The Intravaginal Ejaculatory Latency Time and International Index of Erectile Function scores were compared with baseline values. The patients were scored as having responded to therapy when a 2-fold or greater increase was observed in Intravaginal Ejaculatory Latency Time compared with baseline values after three months. Three genotypes of 5-HTTLPR were studied: LL, LS and SS. The appropriateness of the allele frequencies in 5-HTTLPR were analyzed according to Hardy-Weinberg equilibrium using the chi(2)-test. RESULTS: The short (S) allele of 5-HTTLPR was significantly more frequent in responders than in nonresponders (p

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. Reactive oxygen species are important mediators of GEN-induced nephrotoxicity. Because of the strong antioxidant properties of pomegranate extract (PE), we evaluated the protective effect of PE against GEN-induced nephrotoxicity. Thirty-two adult male rats were randomly divided into four equal groups: (1) controls; (2) treated with GEN for 14 consecutive days (100 mg/kg/day); (3) treated with GEN plus distilled water; and (4) treated with GEN plus PE (100 μL). After 15 days, the rats were killed and their kidneys were taken, and blood analysis was performed. Tubular necrosis and interstitial fibrosis scores were determined histopathologically; and biochemically, nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels in kidneys were determined. Urea, creatinine, Na(+), and K(+) levels were investigated in the blood analysis. 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 rats in the control and the GEN + PE-treated groups. The GSH level in renal tissue of only GEN-treated rats was significantly lower than those in the control group, and administration of PE to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and PE had significantly lower MDA levels in kidney cortex tissue than those given GEN alone. There was no significant difference of NO levels between the groups. In rats treated with GEN + PE, despite the presence of mild tubular degeneration and tubular necrosis is less severe, and glomeruli maintained a better morphology when compared with the GEN-treated group. We think that PE prevents kidney damage by decreasing oxidative stress in kidney.

The aim of this study was to investigate whether the amount of urinary albumin concentration (UAC) or urinary albumin to creatinine ratio (UACR) is more strongly associated with angiographically documented coronary artery disease (CAD).A total of 199 consecutive patients [11 9(60%) male, 80 (40%) female, mean age =57±10] undergoing diagnostic coronary angiography were included in the study. Significant coronary artery disease was defined as a stenosis equal to or above 50% in the main coronary artery or in one of the other branches. UAC and UACR were calculated from the urine. Baseline clinical parameters, UAC and UACR were compared between subjects with and without CAD. Factors predicting CAD were evaluated by multivariate analysis.Baseline clinical and laboratory characteristics of patients with and without CAD were not different except for a slightly male predominance in patients with CAD. Patients with CAD had significantly higher UACs and UACRs than patients without CAD (32.14±31.27 mg/day vs. 15.61±16.70 mg/day, p=0.01; 9.11±7.42 mg/g vs. 4.80±3.28 mg/g, p=0.009). A positive correlation was found between Gensini score and UACR (p=0.01), whereas no correlation was found between Gensini and UAC. UACR was the only significant parameter for the presence of CAD in the multivariate analysis adjusted for age, sex, other well known CAD risk factors, UAC and UACR.Our preliminary results suggest that UACR is more closely associated with angiography documented CAD than is the level of UAC itself, but UACR maybe more significantly associated with angiography documented CAD than with the levels of UAC.

The aim of this study was to evaluate the role of the inducible nitric oxide synthase (iNOS), selective nuclear factor-kappaB (NF-kappaB) and p38-mitogene-activated protein kinase (p38-MAPK) on oxalate-induced crystal deposition in renal tubules. The rats were divided into three groups; group 1; control group, group 2; ethylene glycol (EG) group, group 3; EG + pyrrolidine dithiocarbamate (PDTC) group. Rats were sacrified on 7, 15 and 45th days. The iNOS expression, p65/NF-kappaB and p38/MAPK activity, and oxidative stress markers were evaluated in the kidney. Crystal depositions were evident on day 7, mild and severe crystallization were observed on day 15 and 45 in EG group, respectively. There was limited or no crystal formation in the EG + PDTC group. While EG stimulates iNOS, p65/NF-kappaB and p38/MAPK activity in renal tubules, PDTC inhibited it. PDTC prevents crystal depositions in renal tubules by reducing oxidative stress, iNOS, NF-kappaB, and p38-MAPK expression.

In vitro studies have shown that nitric oxide (NO), inhibits sperm motility at high concentrations. In this study we aimed to determine the NO levels in the seminal fluid of patients with infertile varicocele both pre and postoperatively and in the control group, and compare the results. 20 men with varicocele presented to our clinic for primary infertility and 15 normal fertile men as controls were involved to study. NO levels in the seminal fluid were determined as the total nitrite by Griess reaction and results were compared with Mann-Whitney U test. Preoperative and postoperative mean seminal fluid NO levels in patients with varicocele were 114.82 +/- 33.02 micromol/L and 93.17 +/- 27.24 micromol/L, respectively. In the control group it was 89.4 +/- 20.82 micromol/L. There was a statistically significant different between mean preoperative and postoperative seminal NO levels (p0.05), whereas there was no significant difference between mean postoperative seminal NO levels and that of control group (p0.05). According to the results of present study, an increase in the level of seminal NO levels may play a role in the sperm dysfunction in infertile patients with varicocele.

Gentamicin (GM) is still considered to be an important antibiotic against life-threatening, gram-negative bacterial infections despite its known nephrotoxic effects. We aimed to evaluate the potential protective effect of atorvastatin (ATO) against GM-induced nephrotoxicity in rats.The rats were randomly divided into five groups of six animals each: control, GM (100 mg/kg/day), ATO (10 mg/kg/day), GM + ATO, and GM + Vehicle. Kidney function tests, tissue oxidative stress parameters, and histopathological and immunohistochemical studies clarified GM nephrotoxicity.GM caused a marked reduction in renal functions and increased oxidative stress parameters. Histopathological examination revealed tubular necrosis especially in the renal cortex in GM rats. On immunohistochemical evaluation, GM rat showed more intense expressions of mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-kappaB), and inducible nitric oxide synthase (iNOS) compared with control. Kidney function tests and tissue oxidative stress parameters were normalized in the GM + ATO group. Histopathological and immunohistochemical pictures were also greatly ameliorated.ATO acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM via the inhibition of MAPK and NF-kappaB signaling pathways and iNOS expression.

Bacterial translocation (BT) is the passage of viable indigenous bacteria from one site to another, such as from gastrointestinal tract to the normally sterile regional mesenteric lymph nodes and than other internal organs. In this study we aimed to investigate the BT to kidney and the protective effect of nitric oxide (NO) inhibition.A total of 40 adult male Wistar albino rats weighing 320-350g were divided into four equal groups. Group 1 (n = 10): control group, group-2 (n = 10) sham control, group-3 (n = 10) simple obstruction, in which ileum was ligated 1-2 cm proximal to the ileocecal valve, group-4 (n = 10), simple obstruction and treated with L-NAME. Twenty four hour after the operation rats were sacrificed and kidneys were removed by sterile manner and trunk blood obtained for NO analysis. BT was defined as any positive culture from the blood and kidney. Results were compared with Mann- Whitney U test.NO levels in control, sham group, simple obstruction group and obstruction plus L-NAME treated group were 14.04 +/- 0.65 micromol/L, 13.03 +/- 0.080 micromol/L, 31.17 +/- 0.40 micromol/L and 12.24 +/- 0.70 micromol/L, respectively. Renal culture results were negative in all controls and sham operated rats. However, all culture results were positive in obstruction group and in 4 in L-NAME-treated group. The most common microorganism that translocated was E. coli.This experimental study shows that BT to rat rat kidneys occurs in bowel obstruction and this can be inhibited by a NO inhibitor, L-NAME. Further studies are needed to define the clinical significance of these findings on urinary tract infection.

The objective of this study was to evaluate inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB inhibitor (NF-kappaB) expression and the potential chemoprotective effects of an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), against cisplatin-induced testicular damage in rats. Rats were divided into 4 equal groups: group 1, control; group 2, injected with cisplatin (CIS) for 5 days (7 mg/kg/day intraperitoneally [IP]); group 3, injected with PDTC alone; group 4, injected with CIS plus PDTC (100 mg/kg IP). Body and testicular weights, plasma testosterone levels, and histopathologic structure of the testicular tissue were determined. The iNOS and NF-kappaB activity were evaluated immunohistochemically by staining p65 to define NF-kappaB activity. Malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) levels and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue. Body and testicular weights, plasma testosterone levels, activity of GSH-Px, and GSH levels were all significantly decreased, whereas the levels of MDA and NO were significantly increased in rats of the CIS group. PDTC treatment increased plasma testosterone levels. A significant increase in GSH levels and GSH-Px activity and a decrease in MDA and NO levels in testicular tissue were observed in the CIS + PDTC group. Immunohistochemically, there was a marked staining for iNOS and NF-kappaB/p65 expression in rats injected with CIS compared with the control (P < .001). CIS caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant arrest of maturation, and perivascular fibrosis. Moreover, PDTC administration to CIS-treated rats significantly prevented these histopathologic chances, as well. CIS induces iNOS expression through activation of NF-kappaB/p65, and CIS-induced testicular toxicity may be prevented by PDTC, which is a selective NF-kappaB inhibitor.

Acetaminophen (APAP) can cause life-threatening renal damages and there is no specific treatment for APAP-induced renal damage. The aim of this study was to investigate the protective effects of curcumin (CMN) on APAP-induced nephrotoxicity. Nephrotoxicity was induced in male Wistar Albino rats by the administration of a single dose of 1000 mg/kg APAP intraperitoneally (i.p.). Some of these rats also received i.p. CMN (200mg/kg) at 30 min after the administration of APAP. Twenty-four hours after the administration of APAP, all the rats were sacrificed with a high dose of ketamine. Urea and creatinine levels were measured in the blood, and the levels of malondialdehyde (MDA) and glutathione (GSH), and antioxidant enzyme activity were determined in the renal tissue. Histopathological changes were studied. APAP administration caused elevated levels of renal MDA, and marked depletion of GSH levels and antioxidant enzyme activity, and deteriorated the renal functions as assessed by the increased plasma urea and creatinine levels as compared to control rats. CMN markedly reduced the elevated MDA levels, significantly increased the antioxidant enzyme activity and normalized the altered renal morphology in rats treated with APAP. CMN might be a potential candidate agent against APAP-induced nephrotoxicity, but further studies are required to identify this issue before clinical application becomes possible.

Objective To evaluate the effect of melatonin on cyclophosphamide (CP)- and cisplatin-induced testicular toxicity with use of sperm parameters and biochemical and histopathologic approaches. Design Experimental study. Setting Vakif Gureba Hospital, Istanbul, Turkey. Animals Six-week-old adult male Wistar albino rats (N = 48). Intervention(s) Cyclophosphamide was administered to rats by gavage at a single dose of 100 mg/kg body weight, only once. Cisplatin was injected intraperitoneally at single doses of 7 mg/kg/d for five consecutive days. Melatonin was both administered separately and coadministered with CP and cisplatin intraperitoneally at a dose of 10 mg/kg body weight. Main Outcome Measure(s) Body and testicular weight, epididymal sperm characteristics, plasma T, and histopathologic structure of the testicular tissue were determined. Malondialdehyde (MDA) and reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue. Result(s) Body and testicular weight, epididymal sperm count, motility and morphology, plasma T levels, the activities of GSH-Px, and GSH levels were significantly decreased whereas the level of MDA was significantly increased in rats of the CP and cisplatin group. Melatonin treatment increased GSH levels and GSH-Px activity, decreased MDA level in testicular tissue, and increased plasma T level. Cyclophosphamide and cisplatin caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant maturation arrest, and perivascular fibrosis. Melatonin significantly improved histopathologic changes. Conclusion(s) Melatonin may prevent CP- and cisplatin-induced testicular damage.

Nephrotoxicity is one of the most important complications of anticancer treatment. Ifosfamide, platinum and methotrexate (MTX) affect renal tubular epithelial cells. Nitric oxide (NO) serves many functions within the kidney. Adrenomedullin (AM) is a potent vasodilator peptide, and may function as a circulating hormone and an autocrine/paracrine mediator involved in the regulation of the cardiovascular system, blood pressure, and renal function. It also has a renoprotective effect and inhibits the generation of reactive oxygen metabolites. To our knowledge, no studies have investigated the effects of anticancer drugs on levels of AM and NO. We investigated the effects of these drugs on the levels of AM and total nitrite, a stable product of NO, and their relations to renal functions. The study was performed in 18 patients (13 males, 5 females) who received chemotherapeutic regimens including high-dose MTX or ifosfamide and platinum. Total nitrite was quantitated by means of the Griess reaction, while AM level was measured by high performance liquid chromatography (HPLC). Plasma total nitrite level (micromol/L) was decreased after chemotherapy (78.73 +/- 47.28 vs. 46.69 +/- 13.89, p: 0.002). A statistically significant difference was found between fractional excretion (FE) of total nitric oxide (FE(NO)) before and after chemotherapy (25.89 +/- 23.11 vs. 51.74 +/- 40.01, p: 0.008). The differences in plasma AM levels (pmol/ml) before (25.07 +/- 4.98) and after (30.20 +/- 1.39) chemotherapy were also statistically significant (p: 0.005). FE(AM) after chemotherapy (1.41 +/- 1.01) was found to be higher than before chemotherapy (0.64 +/- 0.43) (p: 0.000). Our results indicate that some chemotherapeutic agents (high-dose MTX, ifosfamide, and cisplatinium) may cause renal tubular damage. FE(AM) and FE(NO) may also be used for the detection of subclinical acute tubular nephrotoxicity. However, further detailed researches will be necessary to establish the certain role of NO and AM in toxicities of chemotherapeutic agents.

Nitric oxide (NO) is a free oxygen radical with powerful vasodilator properties studied in many tissues. It is produced by NO synthases in endothelial cells upon stimulation by various agents like cytokines and tumor necrosis factor. The end-products of NO are nitrite and nitrate. Their levels are used biochemically to determine NO synthase activity. Evidence is accumulating for the role of NO in the pathophysiology of inflammatory Behcet’s disease (BD). Indeed, we first demonstrated that serum NO production is increased in active BD, suggesting a possible new activity marker. More recently, we have reported that pro-inflammatory cytokines, inducers of NO, and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in BD. Our findings were then supported by four independent investigations, one of which was from the present group. 7 Moreover, aqueous humor NO levels were found to be increased in uveitic BD patients. Furthermore, Salvarani et al . have recently shown that the GluAsp298 polymorphism of endothelial NO synthase gene is associated with BD susceptibility. Therefore, to support our previous studies, this report further investigated for the first time NO levels in red blood cells of BD patients compared with age-matched and sex-matched healthy control volunteers. A total of 20 patients with BD (16 men, four women), with a mean age of 33.4 years, and 15 healthy control subjects (12 men, three women), with a mean age of 32.1 years, were enrolled in this study. Patients with BD had to fulfil the International Study Group criteria for the diagnosis of BD. Fasting whole-blood samples were taken from BD patients and control subjects by venipuncture from an antecubital peripheral vein into heparinised plain tubes to prepare the erythrocyte sediment. The buffy coat on the erythrocyte sediment was carefully separated. The erythrocyte sediment was subsequently washed three times with 10-fold volumes of 0.9% sodium chloride solution to remove the plasma remnants. Following this, the erythrocyte sediment was treated with four-fold volumes of ice-cold deionised water to obtain hemolysate. NO is a labile compound and has a brief half-life, and therefore its detection as the native NO molecule is difficult. It is rapidly converted to the stable end-products nitrate (NO3 ) and nitrite (NO2 ) in typical oxygenated aqueous solutions and tissues. Thus, erythrocyte total nitrite levels were measured as an index of NO production. For total nitrite detection, lysate was treated with copperised cadmium in glycine buffer at pH 9.7 (2.5 /3.0 g of cadmium granules for a 4 ml reaction mixture) to reduce NO3 to NO2 . Measurement of total nitrite was based on the Griess reaction, in which a chromofore with a strong absorbance at 540 nm is formed by the reaction of nitrite with a mixture of sulphanilamide and N -(1Letter