Is serum level of nestin useful in detecting epithelial ovarian cancer?

AIM: The aim of the present study was to evaluate the usefulness of nestin as a discriminative marker between benign and malignant ovarian tumors. METHODS: During the 1 year from January 2015 through December 2015, a nonconsecutive series of 80 patients (40 malignant, 40 benign) who underwent surgery for an adnexal mass were enrolled in the study. Intraoperative frozen section evaluation was performed if there was a suspicion in diagnosis. Statistical analyses were performed using spss ver. 16.0, while clinicopathological variables, including the categorical data, were analyzed using the χ2 -test or Fisher's exact test. A P-value < 0.05 was defined as statistically significant. RESULTS: Preoperative serum carbohydrate antigen (CA)-125, CA-15-3, and nestin levels were significantly higher in the malignant group compared to patients with benign ovarian tumors (P < 0.001, respectively). Serum nestin levels did not differ significantly on the basis of histologic subtypes. Serum nestin levels had specificity of 89.7%, which demonstrates nestin's sufficiency to distinguish benign from malignant epithelial ovarian tumors. The positive likelihood ratio of nestin was found to be superior to that of CA-125 and CA-15-3. CONCLUSION: The results obtained from our study suggest that measurement of nestin level, alongside physical examination, transvaginal ultrasound, and serum CA-125 and CA-15-3 levels, can help differentiate benign ovarian tumors from malignant epithelial ovarian tumors. The findings of our study need to be supported with additional studies.

Gender and chronological age affect erythrocyte membrane oxidative indices in citrate phosphate dextrose adenine-formula 1 (CPDA-1) blood bank storage condition.

It is well known that in vitro storage lesions lead to membrane dysfunction and decreased number of functional erythrocytes. As erythrocytes get older, in storage media as well as in peripheral circulation, they undergo a variety of biochemical changes. In our study, the erythrocytes with different age groups in citrate phosphate dextrose adenine-formula 1 (CPDA-1) storage solution were used in order to investigate the possible effect of gender factor on oxidative damage. Oxidative damage biomarkers in erythrocyte membranes such as ferric reducing antioxidant power, pro-oxidant-antioxidant balance, protein-bound advance glycation end products, and sialic acid were analyzed. Current study reveals that change in membrane redox status during blood-bank storage condition also depends on both gender depended homeostatic factors and the presence of CPDA-1. During the storage period in CPDA-1, erythrocytes from the male donors are mostly affected by free radical-mediated oxidative stress but erythrocytes obtained from females are severely affected by glyoxidative stress.

Fluoxetine ameliorates imbalance of redox homeostasis and inflammation in an acute kidney injury model

Ischemia-reperfusion (IR) has been reported to be associated with augmented reactive oxygen radicals and cytokines. Currently, we aimed to examine the influence of fluoxetine, which is already used as a preoperative anxiolytic, in the context of IR induced by occlusion of infrarenal abdominal aorta (60 min of ischemia) and its effects on renal oxidative status, inflammation, renal function, and cellular integrity in reperfusion (120 min post-ischemia). Male rats were randomly assigned as control, IR, and pretreated groups. The pretreated group animals received fluoxetine (20 mg/kg, i.p.) once daily for 3 days. Renal tissue oxidative stress, myeloperoxidase activity, proinflammatory cytokines (tumor necrosis factor-alfa, interleukin-1beta, interleukin-6), histology, and function were assessed. As an anti-inflammatory cytokine, interleukin-10 was also assessed. IR led to a significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant antioxidant balance and decrease in superoxide dismutase activity and ferric reducing/antioxidant power level (p < 0.05), but fluoxetine was able to restore these parameters. High concentrations of tumor necrosis factor-alfa, interleukin-1beta, interleukin-6, and myeloperoxidase activity caused by IR were significantly decreased in kidney tissue with fluoxetine. In addition, interleukin-10 levels were high in fluoxetine pretreated group. IR resulted in disrupted cellular integrity, infiltration of tissue with leukocytes, and decreased serum creatinine-urea levels (p < 0.05). Fluoxetine significantly restored impaired redox balance and inflammation parameters of rats subjected to IR to baseline values. This beneficial effect of fluoxetine on redox balance might be addressed to an improvement in renal function (AU)

Fluoxetine ameliorates imbalance of redox homeostasis and inflammation in an acute kidney injury model.

Ischemia-reperfusion (IR) has been reported to be associated with augmented reactive oxygen radicals and cytokines. Currently, we aimed to examine the influence of fluoxetine, which is already used as a preoperative anxiolytic, in the context of IR induced by occlusion of infrarenal abdominal aorta (60 min of ischemia) and its effects on renal oxidative status, inflammation, renal function, and cellular integrity in reperfusion (120 min post-ischemia). Male rats were randomly assigned as control, IR, and pretreated groups. The pretreated group animals received fluoxetine (20 mg/kg, i.p.) once daily for 3 days. Renal tissue oxidative stress, myeloperoxidase activity, proinflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, interleukin-6), histology, and function were assessed. As an anti-inflammatory cytokine, interleukin-10 was also assessed. IR led to a significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant antioxidant balance and decrease in superoxide dismutase activity and ferric reducing/antioxidant power level (p < 0.05), but fluoxetine was able to restore these parameters. High concentrations of tumor necrosis factor-α, interleukin-1ß, interleukin-6, and myeloperoxidase activity caused by IR were significantly decreased in kidney tissue with fluoxetine. In addition, interleukin-10 levels were high in fluoxetine pretreated group. IR resulted in disrupted cellular integrity, infiltration of tissue with leukocytes, and decreased serum creatinine-urea levels (p < 0.05). Fluoxetine significantly restored impaired redox balance and inflammation parameters of rats subjected to IR to baseline values. This beneficial effect of fluoxetine on redox balance might be addressed to an improvement in renal function.

The effect of fluoxetine on ischemia-reperfusion after aortic surgery in a rat model.

BACKGROUND: Aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute lung injury after abdominal aortic surgery. The aim of the present study was to examine the effect of fluoxetine (Flx), a selective serotonin reuptake inhibitor widely used as a preoperative anxiolytic, on lung injury induced by abdominal aortic IR in rats. METHODS: Wistar rats were randomized into three groups (n = 7 per group): (1) control (sham laparotomy); (2) IR without Flx (60-min ischemia and 120-min reperfusion); (3) IR with Flx (Flx + IR) (Flx 20 mg/kg/d, intraperitoneally for 3 d before surgery). Lung tissue samples and bronchoalveolar lavage (BAL) were obtained for biochemical analysis of oxidative status. Ischemia-modified albumin (IMA) level and protein concentrations in BAL and lung wet to dry weight ratios were determined. Histologic evaluation of the lung tissues was also performed. RESULTS: IR without Flx led to significant increase in lipid hydroperoxide, malondialdehyde, and pro-oxidant-antioxidant balance and decrease in superoxide dismutase, glutathione, and ferric reducing antioxidant power activities (P < 0.05 versus control), whereas Flx was able to restore these parameters (P > 0.05 versus control) and decrease IMA level (P < 0.01 versus control) and protein concentration (P < 0.05 versus control) in BAL and wet to dry lung weight ratio. Histologic evaluation showed that Flx attenuated the morphologic changes associated with lung injury. CONCLUSIONS: The results indicate that Flx confers protection against aortic IR-induced lung oxidative stress and cellular integrity. IMA levels in BAL may be used as a follow-up marker for the efficacy of treatment in lung injury.

The effect of chronic long-term intermittent hypobaric hypoxia on bone mineral density in rats: role of nitric oxide.

Intermittent hypoxia is the most common pattern of hypoxic exposure in humans. The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on bone metabolism is not investigated. We examined the effect of CLTIHH on bone metabolism and the role of nitric oxide (NO) in this process. The rats were divided into three groups in this study. The animals in groups I and II have been exposed to CLTIHH. The animals in group II were also treated with nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mm Hg; 5 h/day, 5 days/week, 5 weeks). The group III (control) rats breathed room air in the same environment. At the begining of the experiments, bone mineral density (BMD) of the animals were measured, and blood samples were collected from the tail vein. After the 5-week CLTIHH period, the same measurements were repeated. Parathyroid hormone, calcium, phosphate, bone alkaline phosphatase (b-ALP), NO, interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha levels were determined. The cytokines, NO levels, and BMD in CLTIHH-induced rats were higher compared with baseline and control values. The cytokines, b-ALP, and BMD increased while NO levels decreased in the group II compared with baseline values. BMD values of group II were lower than group I but higher than control group. Our results suggested that CLTIHH has positive effects on bone density. Intermittent hypoxia protocols may be developed for treatment and prevention of osteopenia and osteoporosis.

Increased maternal serum and cord blood fibronectin concentrations in preeclampsia are associated with higher placental hyaluronic acid and hydroxyproline content.

BACKGROUND: Total or cellular fibronectin (FN) determinations have been used to differentiate between normal and preeclamptic pregnants. The purpose of this study was to examine the relationship between maternal serum FN levels and the extracellular matrix molecule contents of placental tissue, such as FN, hyaluronic acid (HA) and hydroxyproline (HP) levels. MATERIAL AND METHODS: We obtained maternal blood samples and placental tissue samples from healthy (n = 17, controls) and preeclamptic pregnants (n = 29). We also obtained cord blood samples for FN and HA determination from the same patients. FN and HA concentrations in the placenta and maternal and cord blood were measured by and enzyme-linked immunosorbent assay and HP contents in the placenta were measured by a colorimetric assay. RESULTS: FN levels in maternal serum, cord blood, and placenta were significantly higher in preeclamptics than in controls (p<0.001, p<0.001 and p<0.05, respectively). HA concentrations in the cord blood and placenta were found to be elevated in preeclamptics (p<0.05 and p<0.01). Preeclamptics had significantly higher placental HP levels than controls (p<0.001). Similar statistically significant results were obtained when the pregnant subjects classified as nulliparous and multiparous. There was no difference in ECM molecule levels between nulliporous and multiparous women in preeclamptic pregnant group. In regression analysis maternal serum FN levels were correlated with placental HA and HP levels (p<0.01 and p<0.01). There was a positive correlation between cord blood FN and both placental HP (p<001) and HA levels (p<0.01). FN levels in maternal serum, cord blood, and placenta were also negative correlated with fetal birth weight (p<0.01, p<0.05 and p<0.05, respectively). CONCLUSION: FN in maternal serum, cord blood, and placenta is increased with elevated placental HA and HP levels, probably reflecting placental basement membrane alterations during preeclampsia.

Plasma protein carbonyl and thiol stress before and after laparoscopic gastric banding in morbidly obese patients.

BACKGROUND: The aim of this study is to examine the relationship between oxidative plasma protein and thiol stress and weight loss after laparoscopic adjustable gastric banding (LAGB). METHODS: Plasma protein carbonyl (PCO) concentration as a marker of protein oxidation, plasma thiol (P-SH) and erythrocyte glutathione concentration (GSH, major intracellular thiol), as an antioxidant and metabolic markers, such as Homeostatic Model Assessment - Insulin resistance (HOMA-IR), BMI and plasma lipids were determined in morbidly obese patients (n 22, mean age 34.7 +/- 11 years, BMI 48.4 +/- 6.4 kg/m2) at baseline and 1 and 6 months after operation. Baseline levels in patients were also compared with the levels in age-matched controls (n 20, BMI 21.3 +/- 1.8 kg/m2). Plasma PCO and thiols and erythrocyte GSH concentrations were determined spectrophotometrically. RESULTS: Plasma PCO were significantly higher and plasma and erythrocyte thiol concentrations were significantly lower in morbidly obese patients than in controls (for each comparison, P<0.01). BMI, plasma triglycerides and HOMA-IR were positively correlated with plasma PCO and negatively correlated with plasma P-SH and erythrocyte GSH (for each comparison, P<0.01). Plasma HDL-cholesterol levels were positively correlated with plasma erythrocyte GSH (r = 0.405, P<0.01) and negative correlated with plasma PCO (r = -0.273, P<0.01). One and 6 months after the LAGB operation, total weight loss was 13.2 +/- 6.3 and 35.5 +/- 7.5 kg, respectively. Plasma PCO concentrations were decreased and P-SH and erythrocyte GSH concentrations were elevated following weight loss (for each, P<0.01). Only plasma P-SH levels were restored to the control levels 6 months after LAGB. CONCLUSIONS: Obesity and insulin resistance appear to be associated with plasma protein oxidation and thiol concentrations. Protein and thiol oxidative stress was improved by weight loss after LAGB in the short-term.

Oxidative stress and nitric oxide in rats with alcohol-induced acute pancreatitis.

AIM: Oxygen free radical mediated tissue damage is well established in pathogenesis of acute pancreatitis (AP). Whether nitric oxide (NO) plays a deleterious or a protective role is unknown. In alcohol-induced AP, we studied NO, lipooxidative damage and glutathione in pancreas, lung and circulation. METHODS: AP was induced in rats (n = 25) by injection of ethyl alcohol into the common biliary duct. A sham laparatomy was performed in controls (n = 15). After 24 h the animals were killed, blood and tissue sampling were done. RESULTS: Histopathologic evidence confirmed the development of AP. Marked changes were observed in the pulmonary tissue. Compared with controls, the AP group displayed higher values for NO metabolites in pancreas and lungs, and thiobarbituric acid reactive substances in circulation. Glutathione was lower in pancreas and in circulation. Glutathione and NO were positively correlated in pancreas and lungs of controls but negatively correlated in circulation of experimental group. In the experimental group, plasma thiobarbituric acid reactive substances were negatively correlated with pancreas thiobarbituric acid reactive substances but positively correlated with pancreas NO. CONCLUSION: NO increases in both pancreas and lungs in AP and NO contributes to the pathogenesis of AP under oxidative stress.