Protective Effect of Selenium Against Cisplatin-Induced Ototoxicity in an Experimental Design.

Cisplatin is an effective chemotherapeutic agent in the treatment of several types of malignant solid tumors but its clinical use is associated with ototoxicity. In the present study, we investigated the effect of selenium administration on lipid peroxidation (malondialdehyde [MDA]) and cisplatin-induced ototoxicity in rats. Healthy wistar albino rats (n = 21) were randomly divided into 3 groups: control (C), cisplatin (Cis), cisplatin and selenium (Cis+Se). Cisplatin was administered for 3 days to Cis and Cis+Se groups. Cis+Se group received selenium 5 days before cisplatin injection and continued for 11 consecutive days. Hearing thresholds and lipid peroxidation (MDA) levels of the rats were recorded before injections and at the end of experimental protocol. The cochleas of animals were harvested for histologic and immunuhistochemical examinations. In biochemichal analyses, pretreatment with selenium prevented the elevation of MDA levels in Cis+Se group rats. Moreover, animals in Cis+Se group had better hearing threshold levels than animals in cis group. Samples obtained from the animals in Cis group revealed extensive loss of the normal microarchitecture of the organ of Corti. On the other hand, animals in Cis+Se group exhibited a preservation of the morphology of the organ of Corti and outer hair cells. In the immunohistochemical examinations of cochlear tissues stained with anti-caspase-3, a higher degree of immunopositivity was found in the Cis group. When Cis+Se group and Cis group were compared, significantly less immunopositivity occurred in the Cis+Se group (P < 0.05). Thus, it appears that pretreatment with selenium may reduce cisplatin-induced ototoxicity in rats.

The effect of positive end-expiratory pressure on inflammatory cytokines during laparoscopic cholecystectomy.

OBJECTIVES: To investigate effects of the positive end-expiratory pressure (PEEP) application of 10 cm H2O on the plasma levels of cytokines during laparoscopic cholecystectomy. METHODS: A prospective study was conducted on 40 patients who presented to the Department of General Surgery, Medical Faculty, Turgut Özal University, Ankara, Turkey scheduled for laparoscopic cholecystectomy operation during a 10 month period from September 2012 to June 2013. Forty patients scheduled for laparoscopic cholecystectomy operation were randomly divided into 2 groups; ventilation through zero end-expiratory pressure (ZEEP) (0 cm H2O PEEP) (n=20), and PEEP (10 cm H2O PEEP) (n=20). All patients were ventilated with 8 ml/kg TV. Levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL 10, and transforming growth factor (TGF)-ß1 were measured in the pre- and post-operatively collected samples. RESULTS: Blood samples of 30 patients' were analyzed for plasma cytokine levels, and 10 were excluded from the study due to hemolysis. Post-operative plasma IL-6 levels were observed to be significantly higher than the pre-operative patients (p=0.035). Post-operative plasma TGF-ß1 levels in the PEEP group was found significantly higher compared with the pre-operative group levels (p=0.033). However, there were no significant differences in the pre- and post-operative plasma cytokine levels between the 2 groups. CONCLUSION: The application of PEEP of 10 cm H2O, which has known beneficial effect on respiratory mechanics, does not have any effect on systemic inflammatory response undergoing pneumoperitoneum during laparoscopic cholecystectomy surgery.

Neutrophil-Lymphocyte Ratio (NLR) Could Be Better Predictor than C-reactive Protein (CRP) for Liver Fibrosis in Non-alcoholic Steatohepatitis(NASH).

BACKGROUND-AIM: Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease worldwide. The aims of this study were to assess Neutrophil-Lymphocyte Ratio (NLR) and C-reactive protein (CRP), and their association with liver histology in patients with non-alcoholic steatohepatitis (NASH), chronic hepatitis B (HBV), and hepatitis C (HCV). MATERIAL-METHODS: We studied 38 consecutive patients with biopsy-proven NASH, 19 patients with HCV, 45 patients with HBV, and 35 healthy controls who were similar for age and gender. The stage of fibrosis was measured using a 6-point scale. RESULTS: NLR was significantly higher in NASH patients compared to controls, HBV, and HCV patients (p<0.001, p<0.001, and p<0.001, respectively). NLR was positively associated with NAFLD activity scores (r=0.861, p<0.001). NLR was associated with hepatocyte ballooning degeneration (r=0.426, p=0.024), lobular inflammation(r=0.694, p<0.001), steatosis(r=0.498, p=0.007), and fibrosis stage(r=0.892, p<0.001) in NASH patients. Univariate and multivariate analyses showed that NLR was significantly associated with liver fibrosis and NAS (ß=0.631, p<0.001 for liver fibrosis; ß=0.753, p<0.001 for NAS in the multivariate model); however, CRP had no association with liver fibrosis and NAS CONCLUSION: NLR is a promising and inexpensive inflammation marker that correlates with histological grade and fibrosis stage in NASH patients.

Gut satiety hormones and hyperemesis gravidarum.

UNLABELLED: Hyperemesis gravidarum (HG) is described as unexplained excessive nausea and vomiting during pregnancy. Some gut hormones that regulate appetite may have important role in etiopathogenesis of HG and weight changes during pregnancy. In this study, levels of gut satiety hormones were evaluated in pregnant women with HG. METHODS: This prospective case-control study was conducted in 30 women with HG and 30 healthy pregnant women without symptoms of HG. Fasting venous blood samples were taken from all subjects for measurement of plasma gut hormone levels; obestatin (pg/mL), peptide YY (PYY), pancreatic polypeptide (PP) and cholecystokinin (CCK). RESULTS: Plasma PYY and PP levels were significantly higher in HG group. The most important parameter in diagnosis of HG was plasma PP level. Simple use of PP level led to the diagnosis 91.1 % of HG cases correctly. The single most important parameter in the prediction of HG was also PP level. CONCLUSION: Anorexigenic gut hormones might have important role in etiopathogenesis of hyperemesis gravidarum and weight changes during pregnancy.

Cilostazol attenuates spinal cord ischemia-reperfusion injury in rabbits.

OBJECTIVE: The aim of this study was to evaluate the pretreatment effect of cilostazol on spinal cord ischemia-reperfusion injury. DESIGN: Prospective, interventional study. SETTING: Research laboratory, single institution. PARTICIPANTS: Twenty-four New Zealand white rabbits. INTERVENTIONS: Twenty-four rabbits were divided into 3 equal groups: group I (sham), group II (ischemia-reperfusion, control group), and group III (cilostazol, administered orally 30 mg/kg/day for 3 days before the surgery). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the iliac bifurcation for 30 minutes. Seventy-two hours postoperatively, the motor function of the lower limbs was evaluated in each animal according to the modified Tarlov score. Spinal cord and blood samples were taken for histopathologic and biochemical analyses at the 72nd hour of reperfusion. MEASUREMENTS AND MAIN RESULTS: All rabbits in the ischemia-reperfusion group (group II) showed severe neurologic deficits. The median (IQR) Tarlov scores postoperatively at 72 hours in groups I, II, and III were 5.0(-), 2.0(1.0), and 4.5(1.0), respectively. Administration of cilostazol resulted in a significant reduction in motor dysfunction when compared with the ischemia-reperfusion group (p<0.001). In the ischemia-reperfusion group, serum and tissue glutathione peroxidase and superoxide dismutase activity were significantly less compared with the sham group (group I) (p<0.05). Serum and tissue glutathione peroxidase and superoxide dismutase levels in the cilostazol-treated group (group III) were higher compared with the ischemia-reperfusion group (p<0.05). In the cilostazol-treated group, serum and tissue malondialdehyde levels were lower compared with the ischemia-reperfusion group (p<0.05). Histopathologic analysis found decreased neuronal injury in the cilostazol group when compared with the ischemia-reperfusion group (p< 0.05). CONCLUSIONS: This study showed that pretreatment with cilostazol significantly ameliorated neurologic functional outcome and attenuated neuronal histopathologic injury after transient aortic occlusion in rabbits.

Effect of anti-vascular endothelial growth factor antibody during early fetal development in rats.

OBJECTIVE: To examine the effect of anti-vascular endothelial growth factor (VEGF) antibody Bevacizumab during early fetal development in rats. METHODS: Presumed-pregnant rats received single intraperitoneal injection of Bevacizumab (0-20 mg/kg) on gestational day (GD) 3, 7, and 14 (n = 2 rats/group). After Study 1 (dose range finding study), Study 2 performed with intraperitoneal 20 mg/kg bevacizumab or saline on GD 7 (n = 6 rats/group including the Study 1). Blood samples were collected 3 and 7 d after the injection. Uterus and ovarian tissues were obtained 7 d after the injection. Number of gestational sacs (GS), size of GS and fetus, serum rat ß chorionic gonadotropin (ß-CG), and platelet endothelial cell adhesion molecule (PECAM) for immunohistochemical assessment of angiogenesis were evaluated. RESULTS: Number of GS, size of GS, and fetus were lower in the study group than the control group. Serum rat ß-CG levels were significantly increased in the control group and significantly decreased in the study group. Staining densities for PECAM in vascular structures in both corpus luteum and placenta were lower in the study group than the control group. CONCLUSION: Anti-VEGF antibody has an inhibitory effect on pregnancy development and caused litter death.

Ischemia-modified albumin may be a novel marker for the diagnosis and follow-up of necrotizing enterocolitis.

AIM: We investigate the efficacy of serial ischemia-modified albumin (IMA) measurements in diagnosis and follow-up of necrotizing enterocolitis (NEC), and compare its effectiveness with C-reactive protein (CRP), interleukin-6 (IL-6), in NEC. METHODS: Preterm infants, whose gestational age and weight matched each other, were grouped as control (n = 36) and NEC (n = 37). IMA, CRP, IL-6 levels were measured on the third day of life for the control group and on the day of diagnosis (first day), third, and seventh days of NEC. RESULTS: IMA, CRP, and IL-6 levels were significantly increased in NEC patients compared to the control group (P < 0.001) on the follow-up. IMA levels were significantly higher in infants with stage-III NEC than those in infants with stage-II NEC on the first, third, and seventh days (P < 0.001). The area under curve for IMA (0.815 at diagnosis, 0.933 at the third day, 0.935 at the seventh day) were significantly higher than CRP and IL-6 at all days for predicting perforation in infants with NEC (P < 0.001). Similarly, the area under curve for IMA (0.952 at diagnosis, 0.929 at the third day, 0.971 at the seventh day) was significantly higher than CRP and IL-6 at all consequent days of diagnosis for predicting mortality in infants with NEC (P < 0.001). CONCLUSION: Ischemia-modified albumin was found to be superior to CRP and IL-6 in both diagnosis and follow-up of NEC.

Assessment of early atherosclerotic findings in patients with nasal polyposis.

OBJECTIVE: To investigate early markers of atherosclerosis in patients with nasal polyposis (NP) through measurements of carotid artery intima-media thickness (CIMT), flow-mediated vasodilatation (FMD) of the brachial artery and serum paraoxonase-1 (PON-1) activity. METHODS: Forty-five patients with NP were included in the study group and 45 healthy individuals in the control group. The diagnosis of patients with NP was predicated on anterior rhinoscopy, endoscopic nasal examination and coronal paranasal sinus computed tomography (CT). Measurements of CIMT and FMD of the brachial artery were performed by high-resolution ultrasonography. Serum PON-1 activity was evaluated by measuring the rate of paraoxon hydrolysis. RESULTS: Mean CIMT values were found to be increased in the NP group compared to the control group. However, mean FMD % values and serum PON-1 activity were significantly lower in the NP group compared to the control group. Moreover; the endoscopic polyps' scores and paranasal sinus CT scores were positively correlated with CIMT and negatively correlated with FMD % values and PON-1 activity. Disease duration also was positively correlated with CIMT and negatively correlated with FMD % values. CONCLUSION: Impaired FMD, increased CIMT and decreased serum PON-1 activity may be considered to be risk factors for accelerated atherosclerosis in patients with NP who may have subclinical atherosclerosis and be at risk for cardiovascular events in the future.

Effects of computer monitor-emitted radiation on oxidant/antioxidant balance in cornea and lens from rats.

PURPOSE: This study aims to investigate the possible effects of computer monitor-emitted radiation on the oxidant/antioxidant balance in corneal and lens tissues and to observe any protective effects of vitamin C (vit C). METHODS: Four groups (PC monitor, PC monitor plus vitamin C, vitamin C, and control) each consisting of ten Wistar rats were studied. The study lasted for three weeks. Vitamin C was administered in oral doses of 250 mg/kg/day. The computer and computer plus vitamin C groups were exposed to computer monitors while the other groups were not. Malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities were measured in corneal and lens tissues of the rats. RESULTS: In corneal tissue, MDA levels and CAT activity were found to increase in the computer group compared with the control group. In the computer plus vitamin C group, MDA level, SOD, and GSH-Px activities were higher and CAT activity lower than those in the computer and control groups. Regarding lens tissue, in the computer group, MDA levels and GSH-Px activity were found to increase, as compared to the control and computer plus vitamin C groups, and SOD activity was higher than that of the control group. In the computer plus vitamin C group, SOD activity was found to be higher and CAT activity to be lower than those in the control group. CONCLUSION: The results of this study suggest that computer-monitor radiation leads to oxidative stress in the corneal and lens tissues, and that vitamin C may prevent oxidative effects in the lens.

Oxidant stress due to non ionic low osmolar contrast medium in rat kidney.

BACKGROUND & OBJECTIVES: Contrast media may cause contrast-induced nephropathy (CIN) in risk group. This study was taken up to establish possible effects of non ionic low osmolar contrast medium administration on oxidant/antioxidant status and nitric oxide (NO) levels in rat kidney tissues. METHODS: Fourteen female, 14 wk old Wistar-albino rats were divided into 2 groups of 7 rats each (control and contrast groups). Non ionic low osmolar contrast medium was administered iv to the animals in the contrast group. The day after, animals were sacrificed and malondialdehyde (MDA) and NO levels and activities of antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] and oxidant [xanthine oxidase (XO)] enzymes were measured in kidney tissues. Serum creatinine levels were measured to evaluate kidney functions. RESULTS: Contrast medium administration caused an increase in MDA levels and a decrease in NO levels in kidney tissues. INTERPRETATION & CONCLUSIONS: The results suggest that non ionic low osmolar contrast medium administration leads to accelerated oxidant reactions and decreased NO level in rat kidney tissues. Further studies need to be done to assess the role of these changes in CIN.

Honey prevents hepatic damage induced by obstruction of the common bile duct.

AIM: To examine the possible effects of honey supplementation on hepatic damage due to obstruction of the common bile duct in an experimental rat model. METHODS: The study was performed with 30 male rats divided into three groups: a sham group, an obstructive jaundice group, and an obstructive jaundice plus honey group. At the end of the study period, the animals were sacrificed, and levels of nitric oxide (NO), and NO synthase (NOS) activities were measured in liver tissues, and levels of adenosine deaminase (ADA) and alanine transaminase (ALT) activities were measured in serum. RESULTS: Blood ALT and ADA activities were significantly elevated in the jaundice group as compared to those of the sham group. In the obstructive jaundice plus honey group, blood ALT and ADA activities were significantly decreased as compared to those of the jaundice group. In erythrocytes and liver tissues, NO levels were found to be significantly higher in the obstructive jaundice plus honey group compared to those of the sham group. Additionally, NO levels were found to be significantly higher in liver tissues from the animals in the obstructive jaundice plus honey group than those of the jaundice group. CONCLUSION: Honey was found to be beneficial in the prevention of hepatic damage due to obstruction of the common bile duct.

Effects of aqueous green tea extract on activities of DNA turn-over enzymes in cancerous and non-cancerous human gastric and colon tissues.

AIM: The purpose of this study was to investigate possible effects of green tea extract on the activities of DNA turn-over enzymes, namely adenosine deaminase (ADA) and xanthine oxidase (XO) in gastric and colon tissues from patients with stomach and colon cancer. MATERIALS AND METHODS: Six cancerous and 6 non-cancerous adjacent human gastric tissues, and 7 cancerous and 7 non-cancerous adjacent colon tissues obtained surgically were treated with aqueous green tea extract at 3 different concentrations for 1 hour, and then ADA and XO activities were measured. RESULTS: In all of the tissues, XO activities were found to elevate after treatment with green tea extract. Additionally, ADA activity was found to be inhibited in the cancerous gastric tissues by the green tea extract. Elevated XO and reduced ADA activities due to treatment with green tea extract may lower salvage pathway activity and lead to inhibition in carcinogenesis. CONCLUSION: Our data suggest that green tea may support the medical treatment of stomach and colon cancer.