CO2 Field Flooding May Also Reduce Oxidative Stress in Open Surgery

Purpose: Anemia in chronic kidney disease (CKD) patients is an important risk factor for cardiovascular disease, and treatment of anemia by erythropoiesis-stimulating agent (ESA) has been reported to improved QOL in CKD patients. Many cardiovascular diseases are initiated by endothelial dysfunction. In this study, the influence of ESA on endothelial function was evaluated by measuring flow-mediated dilation (FMD) in anesthetized 5/6 nephrectomized (Nx) rats. Methods: Nx was established in male SD rats (7 weeks old). Continuous erythropoietin receptor activator (C.E.R.A., epoetin beta pegol; 0.6 μg/kg, once every 2 weeks) was subcutaneously administered from 1 week after Nx. Nine weeks later, endothelial function was evaluated by measuring FMD in the femoral artery of anesthetized rats with a high-resolution ultrasound system. FMD was calculated from the change in diameter of the femoral artery following reperfusion after 5 min occlusion. After that, the femoral artery was harvested and used for western blot analysis. Plasma levels of 8-OHdG and hydroperoxide were determined by ELISA and free radical elective evaluator, respectively. Results: C.E.R.A. normalized hemoglobin level of Nx rats (Nx, 12.5±0.5; Nx+C.E.R.A., 14.7±0.6 g/dL; mean ± SE, n=9) at 9 weeks after Nx. No changes in blood pressure or renal function were observed with C.E.R.A. treatment. In anesthetized rats, reperfusion after 5 min of hindlimb ischemia induced an instantaneous increase in femoral blood flow (i.e. reactive hyperemia). Following hyperemia, dilation of the femoral artery (i.e. FMD) was observed, with a maximum increase in dilation relative to baseline diameter occurring 0.5–1 min after reperfusion. C.E.R.A. significantly increased FMD of Nx rats (Nx, 11.8±2.3; Nx+C.E.R.A., 22.4±4.4%; n=9). Endothelium-independent vasodilation induced by nitroglycerin injection was not influenced by C.E.R.A treatment. C.E.R.A. significantly enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) in the femoral artery. Furthermore, Nox4 protein (a NADPH oxidase component) and nitrotyrosine (a marker of peroxynitrite) were significantly decreased in the femoral arteries of C.E.R.A.-treated rats. On the other hand, plasma 8-OHdG and hydroperoxide, which are other markers of oxidative stress, were not influenced by C.E.R.A. treatment. Conclusion: These results demonstrated that C.E.R.A. improved endothelial function in Nx rats, possibly through reduction of regional oxidative stress in the arteries. The endothelial protective effect of ESA might contribute to the improved prognosis in CKD patients treated with ESA.

Ozone medical applications gather strength, day by day. Ozone, in its oxidant status, administered in low doses and in a number of controlled treatments, is able to trigger the endogenous antioxidant systems achieving a redox balance. As such, it is able to control chronic oxidative stress associated with many diseases. Moreover, levels of nitric oxide and pro-inflammatory cytokines, like tumor necrosis factor (TNF-alfa) and interleukin 1 and 6, were able to be modulated by ozone. Also, mitochondrial integrity and functionality was preserved, calcium homeostasis was achieved, adenosine A1 receptors were activated and activity of the superoxide dismutase enzyme was regulated [1]. In this lecture, preclinical and clinical studies of recent researches developed in Cuba are presented. Two topics have been selected: Alcoholism [2,3] and arthritis [4,5]. In today's world, alcoholism is a serious health and social problem, affecting millions of people, without distinction of race, sex, culture or latitude. One diagnostic criterion of alcohol dependence is the appearance of a withdrawal syndrome when alcohol consumption ceases. Experimental studies have demonstrated that many consequences of withdrawal found in animals resemble those observed in humans. Such signs and symptoms of ethanol withdrawal (EW) include enhanced activity of the autonomic nervous system; body posture and motor abnormalities; hyperexcitability of the central nervous system (CNS), including sensory hyperreactivity, convulsion, anxiety, etc. Chronic ingestion of high levels of alcohol may bring about oxidative stress, associated with hepatic alterations, and of CNS, mainly due to the formation, through alcohol metabolism, of free radicals, acetaldehyde, lipid and protein oxidation and their reaction products. The protective effects of ozone on brain injury induced by oxidative stress and behavioral changes in rats, after 2 weeks of EW, were studied [2]. Also, a clinical trial with 10 alcoholic patients (elapsed time after ethanol withdrawal: less or equal than 3 weeks) treated with ozone by rectal insufflation (ozone concentration from 20 to 35 mg/L and volumes from 100 to 150 ml) was performed [3]. In the preclinical study [2], 4 groups of rats (n=10 each one) were settled: I-Control, II-Ethanol, III- Ethanol + Ozone (20 mg/L, dose of 1 mg/kg, 10 sessions by rectal insufflation) and IV- Ethanol + Oxygen. At the end of EW, rats were subjected to behavioral tests followed by brain tissue collection to measure markers of oxidative damage. Ozone increased food consumption, maintained water intake at the same levels as the control group and reestablished cellular redox status. Anxiety, locomotor activity and memory/learning of the rats were improved. Ozone protected the brain against oxidative injury, improving important functions of the CNS. In the clinical study [3], the results demonstrated that ozone improved 70% of the signs from Clinical Institute Withdrawal Scale (CIWA-Ar), mainly those associated to CNS. Ozone efficacy was observed in patients that required pharmacological treatment. Reduction of CIWA-Ar scores and the oxidative stress (p

Survival after laparoscopic surgery versus open surgery for colon cancer: long-term outcome of a randomised clinical trial

Vitamin E Does Not Regress Hypercholesterolemic Atherosclerosis

Radiotoxicity is a serious problem for patients undergoing radiotherapy, so the search for new radioprotective drugs to mitigate its effects is highly relevant. Radioprotectors should have a number of properties, including direct antioxidant action, reduction of oxidative stress, ability to induce DNA repair or inhibit apoptosis, and at the same time not cause their own side effects. Antioxidants based on lithium salts look promising in terms of their properties. The aim of study was to study the radioprotective properties of lithium pyruvate in vitro. Material and Methods. Relatively radiosensitive blood mononuclear cells and relatively radioresistant fibroblasts of 3T3L1 line were used as biomodels for x-ray exposure. Cells were incubated and irradiated in 96-well plates. Lithium pyruvate was used at a final concentration of 1.2 mM. Cells were irradiated at a dose rate of 15 mGy/s in the absorbed-dose range from 0 to 5 Gy using an x-ray unit (anode voltage: 160 kV, average current: 3.5 mA). Cell viability was assessed by MTT test and resazurin test. The evaluation of cell death variants and the level of oxidative stress were determined by cytofluorimetric method. Results. The cytoprotective effect of lithium pyruvate was established. Cytoprotection was manifested in the increased cell survival and decreased oxidative stress level under lithium pyruvate after x-ray in a wide range of absorbed doses. Relatively high efficiency was shown in relation to blood mononuclear cells with an increase in the viable fraction by 5–7 % and a decrease in oxidative stress level during irradiation in the range of 1.0–3.0 Gy. Apoptosis was found to be the main mechanism of cell death after irradiation. Lithium pyruvate reduced the level of apoptosis in cell population under irradiation and chemically induced oxidative stress. Conclusion. Radioprotective effect of lithium pyruvate under x-ray irradiation in vitro has been shown. Reduction of oxidative stress under the action of pyruvate provides a pathogenetic basis for the potential use of this compound as a radioprotector, which requires further studies on in vivo models.

Daily exercise prevents diastolic dysfunction and oxidative stress in a female mouse model of western diet induced obesity by maintaining cardiac heme oxygenase-1 levels

Limited information exists comparing the post-operative complication rate of laparoscopic or open abdominal surgeries in children with sickle cell disease (SCD). The primary objective of this study was to compare the outcomes in children with SCD who required laparoscopic or open abdominal surgery for a cholecystectomy or splenectomy. We conducted a retrospective analysis of laparoscopic and open abdominal surgeries performed in children with SCD (ages 0-20 years) at two medical centers from 1984 to 2004. The primary outcome measures were the rates of post-operative pain and acute chest syndrome (ACS) episodes following laparoscopic or open abdominal surgery. The secondary outcome was length of hospital stay following surgery. We also examined the potential contribution of pre-operative (transfusion) and intra-operative factors (operating time, estimated blood loss, and end-operative temperature) to post-operative SCD-related complications. A total of 140 cases were identified, 98 laparoscopic and 42 open. Episodes of post-operative pain and ACS episodes were comparable between laparoscopic and open procedures (pain: 4% vs. 3%, P = 0.619; ACS: 5% vs. 5%, P = 0.933). Additionally, laparoscopic surgeries were associated with a significantly shorter hospital stay (2.9 vs. 5.4 days, 95% CI -3.7 to -1.4, P < 0.001). There was no difference in the number of hospital readmissions within 1 month of the surgery. For children with SCD who need a cholecystectomy or splenectomy, laparoscopy is the preferred strategy because of a shorter hospital stay with a similar complication rate compared to open surgeries.

Activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) has a neuro-protective effect on ischemic and hemorrhagic stroke. However, the underlying mechanism is not completely understood. We hypothesized that α-7 nAchR agonist protects brain injury after ischemic stroke through reduction of pro-inflammatory macrophages (M1) and oxidative stress. C57BL/6 mice were treated with PHA568487 (PHA, α-7 nAchR agonist), methyllycaconitine (MLA, nAchR antagonist), or saline immediately and 24 hours after permanent occlusion of the distal middle cerebral artery (pMCAO). Behavior test, lesion volume, CD68+, M1 (CD11b+/Iba1+) and M2 (CD206/Iba1+) microglia/macrophages, and phosphorylated p65 component of NF-kB in microglia/macrophages were quantified using histological stained sections. The expression of M1 and M2 marker genes, anti-oxidant genes and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were quantified using real-time RT-PCR. Compared to the saline-treated mice, PHA mice had fewer behavior deficits 3 and 7 days after pMCAO, and smaller lesion volume, fewer CD68+ and M1 macrophages, and more M2 macrophages 3 and 14 days after pMCAO, whereas MLA's effects were mostly the opposite in several analyses. PHA increased anti-oxidant genes and NADPH oxidase expression associated with decreased phosphorylation of NF-kB p65 in microglia/macrophages. Thus, reduction of inflammatory response and oxidative stress play roles in α-7 nAchR neuro-protective effect.

Activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) has a neuro-protective effect on ischemic and hemorrhagic stroke. However, the underlying mechanism is not completely understood. We hypothesized that α-7 nAchR agonist protects brain injury after ischemic stroke through reduction of pro-inflammatory macrophages (M1) and oxidative stress. C57BL/6 mice were treated with PHA568487 (PHA, α-7 nAchR agonist), methyllycaconitine (MLA, nAchR antagonist), or saline immediately and 24 hours after permanent occlusion of the distal middle cerebral artery (pMCAO). Behavior test, lesion volume, CD68+, M1 (CD11b+/Iba1+) and M2 (CD206/Iba1+) microglia/macrophages, and phosphorylated p65 component of NF-kB in microglia/macrophages were quantified using histological stained sections. The expression of M1 and M2 marker genes, anti-oxidant genes and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were quantified using real-time RT-PCR. Compared to the saline-treated mice, PHA mice had fewer behavior deficits 3 and 7 days after pMCAO, and smaller lesion volume, fewer CD68+ and M1 macrophages, and more M2 macrophages 3 and 14 days after pMCAO, whereas MLA's effects were mostly the opposite in several analyses. PHA increased anti-oxidant genes and NADPH oxidase expression associated with decreased phosphorylation of NF-kB p65 in microglia/macrophages. Thus, reduction of inflammatory response and oxidative stress play roles in α-7 nAchR neuro-protective effect.

OBJECTIVEEvaluate the effects of two dipeptidyl peptidase-IV (DPP-4) inhibitors, sitagliptin and vildagliptin, known to have different efficacy on mean amplitude of glycemic excursions (MAGE), on oxidative stress, and on systemic inflammatory markers in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSA prospective, randomized, open-label PROBE design (parallel group with a blinded end point) study was performed in 90 patients with type 2 diabetes inadequately controlled by metformin. The study assigned 45 patients to receive sitagliptin (100 mg once daily; sitagliptin group) and 45 patients to receive vildagliptin (50 mg twice daily; vildagliptin group) for 12 weeks. MAGE, evaluated during 48 h of continuous subcutaneous glucose monitoring, allowed an assessment of daily glucose fluctuations at baseline and after 12 weeks in all patients. Assessment of oxidative stress (nitrotyrosine) and systemic levels of inflammatory markers interleukin (IL)-6 and IL-18 was performed at baseline and after 12 weeks in all patients.RESULTSHbA1c, fasting and postprandial glucose, MAGE, and inflammatory and oxidative stress markers were similar between the groups at baseline. After 12 weeks, MAGE (P < 0.01) was lower in the vildagliptin group than in the sitagliptin group. After treatment, HbA1c and postprandial glucose evidenced similar changes between the groups (P = NS). Vildagliptin treatment was associated with a stronger decrease in nitrotyrosine (P < 0.01), IL-6 (P < 0.05), and IL-18 (P < 0.05) than sitagliptin treatment. Nitrotyrosine and IL-6 changes significantly correlated with changes in MAGE but not in fasting glucose and HbA1c.CONCLUSIONSMAGE reduction is associated with reduction of oxidative stress and markers of systemic inflammation in type 2 diabetic patients. These effects were greater in the vildagliptin group than in the sitagliptin group.

Hepatic and renal toxicity is one of the side effects of doxorubicin used in the antineoplastic treatment. The aim of this study was to determine if leucine supplementation in the diet of Wistar rats treated with doxorubicin has protective hepatic and renal action evidenced by the reduction of oxidative stress. The experiment included 36 rats distributed in four groups, with 8 Control, 8 LEUcina, 10 DOXorubicin and 10 DOX + LEU. Animals from the DOX and DOX + LEU groups were treated with intraperitoneal injections of doxorubicin for two weeks, three times a week, at a cumulative dose of 7.5 mg / kg. The animals of groups C and LEU received intraperitoneal volume of saline daily, similar to that administered with doxorubicin. The LEU and DOX-LEU groups received the amino acid leucine throughout the study plus 5% added to the basal diet. Hepatic and renal tissue oxidative stress was evaluated by the dosages of the antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR) and also reduced levels of glutathione (GSH) and glucose-6-phosphate dehydrogenase (G6PDH); the oxidizing activity was measured by lipid peroxidation (thiobarbituric acid-TBARS). The hepatic collagen content was evaluated in histological analysis using picrosirius red staining; for analysis of the hepatic and renal tissues the Gomori trichrome was used. The results were presented as mean standard error of the mean (EPM), using GraphPad Prism software version 5.0. The results were compared by the Student's t-Test or the analysis of variance (ANOVA), as appropriate. To verify the detected differences between the groups, the Tukey test was used. Differences were considered significant when p <0.05. The results showed that, in the liver, the DOX group compared to the LEU presented higher antioxidant activity of SOD, catalase and Gpx, and GSH levels and lower levels of lipid peroxidation and collagen deposition. The group DOX + LEU compared to the LEU group also presented lower levels of lipid peroxidation and collagen deposition, and finally, the DOX + LEU group, when compared to the DOX group, presented lower oxidant activity and lower antioxidant activity of SOD, catalase, Gpx and GSH. The renal analyzes showed an increase in oxidative stress in the LEU group evidenced by the increase in GR. All experimental groups had a reduction in the total number of glomeruli in relation to the control. There was no change in collagen deposition. It was concluded that the addition of 5% leucine to the diet administered to doxorubicin treated rats showed a hepatoprotective effect. The hypothesis of leucine nephroprotective effect evidenced by the reduction of oxidative stress was not demonstrated.

This study was designed to assess the efficacy of N-acetylcysteine (NAC) on the reduction of oxidative stress in chronic hemodialysis (HD) patients through measurement of total serum anti-oxidant capacity. In this randomized, double-blind, controlled clinical trial, the efficacy and safety of NAC in reduction of oxidative stress was evaluated in 40 chronic HD patients. The study was conducted at the HD Department of the Golestan Hospital, Ahvaz, Iran. Data were analyzed using SPSS version 19. Paired samples test showed that the mean score of the serum level of total anti-oxidant capacity (TAC) increased from 26.39±17.03 to 33.26±18.8 (Pvalue=0.01) and from 24.02±16.47 to 25.38±17.04 (P=0.1) in the NAC and placebo groups, respectively. Difference in the mean TAC changes between groups was statistically significant (P=0.042). In our study, NAC administration could reduce oxidative stress in chronic HD patients. No major side-effects were observed.

The integrity of spermatozoa in the seminal fluid given its parameters (motility, concentration, morphology and vitality) is important for the reproductive function. The oxidative stress can adversely affect the quality of the semen, which causes the damage and dysfunction of the sperm. Thus, a literature review based on Pubmed was held seeking studies that aimed to improve the quality of sperm with the use of antioxidants. The use of certain vitamins and minerals seem to affect the sperm quality. Literature data on single or combined oral use of these micronutrients in improving semen parameters and fertility potential are limited and scarce. Thus, it is essential to develop new studies that enable micronutrient dosages settings, as well as their combinations in improving sperm quality. The use of oral antioxidants has proved to be a promising strategy for a non-invasive treatment that reduces the need to use assisted reproductive technologies; providing lower costs in the management of male infertility.

Current surgical training: simultaneous training in open and laparoscopic surgery

Treatment of people at ultra-high risk for psychosis.