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Long-chain n-3 polyunsaturated fatty acids modulate immune cell functions. The primary objective of this study was to evaluate the impact of different lipid emulsions (LEs) with supplemented doses of fish oil (FO) on serum cytokine concentration and in vitro cytokine production in patients with intestinal failure on home parenteral nutrition (HPNPs). We hypothesized that FO supplementation would diminish lipopolysaccharide (LPS)-stimulated cytokine production. Twelve HPNPs receiving Smoflipid for at least 3 months were given FO (Omegaven) for a further 4 weeks. After this cycle, the patients were randomized to subsequently receive 1 cycle with Lipoplus and 1 cycle with ClinOleic for 6 weeks or vice versa plus 4 weeks of added Omegaven after each cycle in a crossover design. Comparison of the baseline LE regimens showed lower LPS-stimulated production of IL-1β in the HPNPs on Lipoplus than on the Smoflipid and ClinOleic regimens, as well as lower IL-8 compared to the Smoflipid regimen. Omegaven reduced IL-8 concentration in serum under the Lipoplus regimen and diminished LPS-stimulated production of IL-1β under the Smoflipid and ClinOleic. IL-6 and TNF-α production was depressed only in those on Smoflipid. Irrespective of the LE used, the HPNPs compared to the healthy controls showed higher IL-6, IL-8, and TNF-α concentrations in serum and LPS-stimulated production of IL-6 as well as lower n-6/n-3 long-chain polyunsaturated fatty acids in the erythrocyte phospholipids. LPS-stimulated production of IL-6 correlated negatively with the parenteral dose of eicosapentaenoic acid + docosahexaenoic acid. In conclusion, FO-supplemented parenteral nutrition suppresses in vitro cytokine production.

INTRODUCTION: We analyzed concentrations of osteopontin (OPN) in patients with pancreatic ductal adenocarcinoma (PDAC) in order to determine firstly whether it is useful to distinguish between PDAC patients and those with chronic nonhereditary pancreatitis (CP) and type 2 diabetes mellitus (T2DM), and secondly whether OPN concentrations depend on the PDAC stage. METHODS: Groups consisting of 64 patients with PDAC, 71 with CP, 67 with T2DM and 48 healthy controls (CON) were enrolled in the study. Controls were compared with regard to levels of OPN, oxidative stress markers, conventional tumor markers and other biochemical parameters. RESULTS: Levels of OPN were higher in patients with PDAC compared with CP patients ( P< 0.001), T2DM ( P< 0.001) and CON ( P< 0.001). There were increased OPN levels in CP patients in comparison with T2DM ( P< 0.001) and CON ( P< 0.001). Patients with PDAC in stage IV had higher OPN levels than PDAC patients in stage III ( P< 0.01). There was no difference in OPN levels of PDAC patients in stage III compared to patients in stage II. CONCLUSION: Our pilot study demonstrates the usefulness of estimating OPN levels to differentiate between pancreatic cancer and chronic pancreatitis. Higher OPN levels over 102 ng/ml could be a potential diagnostic biomarker for pancreatic cancer.

Markers of oxidative stress and antioxidant status in relation to inflammatory mediators in septic patients (SPs) during the course of sepsis and after recovery were analysed. Patients were 30 critically ill adults in severe sepsis/septic shock, 19 of which completed 3 samplings (S1: within 24 h after onset of sepsis, S7: 7 days after S1, R7: 7 days after clinical recovery). Comparing SPs with healthy controls (HCs), enhanced C-reactive protein, procalcitonin, bilirubin and CuZn-superoxide dismutase activity were found at S1 only. Oxidized low-density lipoprotein, conjugated dienes and nitrotyrosine were increased at S1, culminated at S7 and reverted nearly to HC levels at R7. Reduced catalase activity and serum amyloid were observed at S1 and endured until R7. Increase in IL-6, IL-10 and tumour necrosis factor alpha (TNF-α) with accompanying decrease in apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, selenium, zinc, albumin, paraoxonase 1 and glutathione peroxidase 1 activity appeared at S1 and persisted until R7. TNF-α, IL-10 and markers of oxidative stress were in negative correlation with HDL cholesterol and albumin at R7. After clinical recovery, increased cytokines and decreased antioxidants were accompanied by lower albumin and HDL cholesterol levels. During this important and beneficial period of tissue repair, patients with prolonged persistence of this status are probably more vulnerable to secondary infections and should be dealt with as constituting a high-risk population.

OBJECTIVES Oxidative stress has been implicated in the pathogenesis of chronic pancreatitis (CP) and pancreatic cancer (PC). The study aim was to assess the oxidative stress markers and antioxidant defense system in patients with CP and those with PC. METHODS Activities of superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1) and concentrations of reduced glutathione, conjugated dienes in low-density lipoprotein (CD/LDL) and oxidized LDL (ox-LDL/LDL) were assessed in 50 PC and 50 CP patients and 50 age and sex-matched controls. RESULTS Comparison of PC and CP groups to controls found the following changes: glutathione peroxidase 1 (GPX1) (-20.2%, -25.5%; P < 0.001), glutathione reductase (GR) (-9.5%, -11.9%; P < 0.05), SOD1 (+22.9%; P < 0.01), CAT (-10.6%; P < 0.05), PON1-A (-34.3%, -16.0%; P < 0.001), PON1-L (-44.2%; -17.0%; P < 0.01), conjugated dienes in LDL (CD/LDL) (+20%, +33.3%; P < 0.05) and ox-LDL/LDL (+42.2%, +14.4%; P < 0.05). The patients with PC had changed activities and levels of SOD1 (+24.2%), CAT (-10.4); P < 0.01), PON1-A (-21.7%), PON1-L (-32.9%), and ox-LDL/LDL (+24.3%); (all P < 0.01) compared with the patients with CP. CONCLUSIONS Reduced antioxidant defense system capacity and increased markers of oxidative stress were found in PC and CP. PON1-L and CAT activities, along with ox-LDL/LDL levels, were the independent factors differentiating the patients with PC from the patients with CP.

This study analyzes fatty acid (FA) composition in plasma lipids and erythrocyte phospholipids while comparing septic and non-septic critically ill patients. The aim was to describe impacts of infection and the inflammatory process. Patients with severe sepsis (SP, n = 13); age-, sex- and APACHE II score-matched non-septic critically ill with systemic inflammatory response syndrome (NSP, n = 13); and age-/sex-matched healthy controls (HC, n = 13) were included in a prospective case–control study during the first 24 h after admission to the intensive care unit. In both SP and NSP, lower n-6 polyunsaturated FA (PUFA) accompanied by higher proportions of monounsaturated FA (MUFA) in plasma phospholipids (PPL) was observed relative to HC. MUFA proportion was negatively correlated with n-6 PUFA, high density lipoprotein cholesterol (HDL-C), and albumin. MUFA was positively correlated with C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-10), oxidized low density lipoproteins (ox-LDL), and conjugated dienes (CD). In both SP and NSP, inflammatory and lipid peroxidation markers were significantly higher—CRP (p

Anthracyclines are regarded as some of the most potent oxidative stress inductors. Despite the fact that oxidative stress induction by anthracyclines is believed to be the key factor in anthracycline-related cardiotoxicity, the precise timeline of oxidative stress changes after anthracycline treatment remains unknown. The aim of the present study is to assess the level of oxidative stress after anthracycline therapy in patients with solid tumors.The study population consists of 128 adult patients (14 males, 114 females, mean age 56 ± 10 years) receiving anthracycline chemotherapy for solid tumors. The control group consists of 38 patients (4 males, 34 females, mean age 59 ± 11 years) receiving anthracycline-free chemotherapy for solid tumors.The main activities of antioxidant enzymes (catalase, glutathione peroxidase-1, superoxide dismutase, and paraoxonase-1) and concentrations of conjugated dienes, surrogate markers of oxidative stress level, were established at the baseline and after anthracycline therapy (median 45; IQR 27-69 days after the end of anthracycline therapy) in all patients. By comparing the activities of antioxidant enzymes and the concentrations of conjugated dienes, before and after therapy, changes in oxidative stress level within the time period were established for both study groups. Differences between the study groups, with regard to changes in the activities of antioxidant enzymes and the concentrations of conjugated dienes, were also evaluated.An increase in oxidative stress was observed after the end of anthracycline therapy in patients with solid tumors. However, our study shows that this persistent elevation of oxidative stress after the end of anthracycline therapy is probably not caused by anthracyclines.

Atherogenic dyslipidemia contributes substantially to the residual cardiovascular risk. The aim of this study was to examine the effects of therapeutic doses of n-3 polyunsaturated fatty acids on the three major lipid abnormalities of atherogenic dyslipidemia, i.e. hypertriacylglycerolemia, low HDL cholesterol, and increased levels of small dense LDL particles, as well as on some new risk factors.A total of 60 hypertriacylglycerolemic patients were included in the study. Group S consisted of 36 patients who were already treated with statins, Group N of 24 patients not yet treated. Each patient was examined after six weeks on placebo and six weeks of treatment with n-3 PUFA (eicosapentaenoic and docosahexaenoic acid ethyl esters, 3.0 g/d).Treatment with n-3 PUFA caused a decrease in plasma triacylglycerols (28%, p0.001), and VLDL (-27%, p0.001), an increase in HDL-C (+4%, p0.01), and a decrease in sdLDL cholesterol (-16%, p0.05). These changes were accompanied by a decrease in microalbuminuria (-30%, p0.05), as well as in several parameters of oxidative stress. Analysis of the fatty acids composition of plasma phospholipids showed a significant increase in all n-3 PUFAs examined, accompanied by a decrease in n-6 PUFAs, as well as in monounsaturated acids. No significant differences in the effects of n-3 PUFA were found between the Groups S and N.Our results support the opinion that hypertriacylglycerolemic patients benefit from the treatment with n-3 PUFA which improves several important metabolic factors of cardiovascular risk.

Objective: In the pathogenesis of the metabolic syndrome (MetS), an increase of oxidative stress could play an important role which is closely linked with insulin resistance, endothelial dysfunction, and chronic inflammation. The aim of our study was to assess several parameters of the antioxidant status in MetS. Methods: 40 subjects with MetS and 40 age- and sex-matched volunteers without MetS were examined for activities of superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), paraoxonase1 (PON1), concentrations of reduced glutathione (GSH), and conjugated dienes in low-density lipoprotein (CD-LDL). Results: Subjects with MetS had higher activities of CuZnSOD (p < 0.05) and GR (p < 0.001), higher concentrations of CD-LDL (p < 0.001), lower activities of CAT (p < 0.05) and PON1 (p < 0.05), and lower concentrations of GSH (p < 0.05), as compared with controls. Activity of GPX1 was not significantly changed. Conclusions: Our results implicated an increased oxidative stress in MetS and a decreased antioxidative defense that correlated with some laboratory (triglycerides, high-density lipoprotein cholesterol (HDL-C)) and clinical (waist circumference, blood pressure) components of MetS.

Paraoxonase 1 is believed to play a role in preventing lipid oxidation and, thus, limiting production of proinflammatory mediators. Systemic inflammatory response in sepsis increases oxidative stress and decreases high-density lipoprotein (HDL) concentrations. The objective of this study was to investigate serum paraoxonase 1 activities in critically ill patients with sepsis and after recovery. Serum paraoxonase 1 arylesterase/paraoxonase activities, concentration of total cholesterol, HDL cholesterol (HDL-C) and serum C-reactive protein (CRP) in septic patients of a medical intensive care unit (n = 30) and age/sex-matched outpatient controls without sepsis (n = 30) were analyzed. Paired convalescent samples were also taken 1 week after recovery (n = 11). In septic patients, both arylesterase (88.3 +/- 36.5 vs. 162.1 +/- 44.8 kU/l, P < 0.001) and paraoxonase (75.2 +/- 50.0 vs. 125.2 +/- 69.4 U/l, P < 0.01) paraoxonase 1 activities decreased as compared to controls. Both activities normalized after recovery. Negative correlation was found between CRP and both arylesterase (r = -0.676, P < 0.001) and paraoxonase (r = -0.401, P < 0.01) as well as positive correlation between HDL-C and both arylesterase (r = 0.585, P < 0.001) and paraoxonase (r = 0.405, P < 0.01) paraoxonase 1 activities. The decreased activity of paraoxonase 1 in negative correlation with CRP offers a potentially useful marker of sepsis progress and recovery in critically ill patients.

To investigate the activities of the main antioxidative enzymes and oxidative stress in women with depressive disorder (DD).In 35 drug-naive women with DD and 35 age matched healthy women enzymes superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPX1), glutathione reductase (GR) and paraoxonase (PON1), concentrations of conjugated dienes (CD), reduced glutathione (GSH) and anthropometric and clinical data were investigated.Women with DD were found to have decreased activities of GPX1 (p0.05), decreased concentrations of GSH (p0.05), and increased activities of GR (p0.05), CuZnSOD (p0.001), and concentrations of CD (p0.05). Activity of GPX1 was positively correlated with concentration of GSH (p0.05). Concentrations of CD were positively correlated with TG (p0.01).Our set of depressive women was characterized by changes indicating an increased oxidative stress, as well as by certain features of metabolic syndrome.

Metabolic syndrome (MS) is defined by the clustering of several components (MSC), which include abdominal fat accumulation, impaired glucose homeostasis, hypertriglyceridemia, lowered high-density lipoprotein cholesterol, increased blood pressure, and hyperuricemia. Metabolic syndrome is also accompanied by increased oxidative stress and inflammation as well as by altered composition of esterified fatty acids (FA). Therefore, we have investigated 210 men (categorized into six groups with increasing number of MSC) to find trends in the extent of oxidative stress, FA pattern and frequency of pathological alleles of the selected candidate genes for lipid metabolism. Increasing number of MSC was connected with the raised serum glucose and insulin, increased concentrations of conjugated dienes in low-density lipoprotein (all p < 0.0001), and high frequency of e2 and e4 alleles of the apolipoprotein E gene (p < 0.005). However, the last significance was lost after the adjustment for age. The incidence of 54Thr allele for intestinal isoform of the fatty acid-binding protein (FABP-2) gene was comparable in all groups. The most important findings were the raised content of saturated FA and the increased activities of Delta9 and Delta6 desaturases (all p < 0.0001), and the decreased content of polyunsaturated FA n-6 family and the decreased activity of Delta5 desaturase (both p < 0.001) in connection with increasing number of MSC. In conclusion, the severity of MS is connected with the progression of oxidative stress and the unfavorable changes in the FA composition. These changes are independent of the studied gene polymorphisms.

Introduction Breast cancer (BC), like other malignancies, is associated with chronic increase of oxidative stress (OS). Anthracyclines (ANTS), potent inductors of OS, represent first-line therapy of advanced BC. OS induction by ANTS is believed to be the key factor in ANTS- related left ventricle dysfunction and the subsequent development of heart failure, which are major complications of ANTS therapy. The aim of the present study is to establish the role of malignancy-related OS present before ANTS therapy in the development of changes in echocardiografic (ECHO) parameters after chemotherapy in patients with breast cancer. Patients and methods The study population consists of 99 adult female suffering from breast cancer (mean age 52 ± 12 years) receiving ANTS chemotherapy. Catalase (CAT) activity as a surrogate marker of OS level and ECHO examination were established at the baseline in all patients. Follow-up ECHO examinations were performed at the end of therapy and again one year after the start of therapy. The correlations between baseline CAT activities and changes in ECHO parameters were evaluated. Results Statistically significant correlation between baseline CAT activity and unfavorable change in end-diastolic left ventricle diameter ( r = 0.24; p = 0.02) was observed soon after the ANTS therapy. Statistically significant correlation between baseline CAT activities and unfavorable change in end-diastolic left ventricle diameter (r = 0.30;p = 0.003) was found at one year following the start of ANTS therapy. Conclusion The results of our study suggest a possible correlation between baseline OS level and the future development of morphological cardiac changes after ANTS chemotherapy in patients with breast cancer. Whether pre-treatment levels of OS can predict ANTS induced left ventricle dysfunction and/or the development of heart failure will be shown by a further follow-up of the study population. The study was supported by the grant awarded by Ministry of Health, Czech republic, IGA MZ CR NS 9774-4 Disclosure All authors have declared no conflicts of interest.