Jasmina Ivanisevic

Pulmonary function, oxidative stress and inflammatory markers in severe COPD exacerbation.

BACKGROUND Oxidative stress and inflammation play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). OBJECTIVE Pulmonary function, oxidative stress parameters and inflammatory markers were measured in 74 patients with severe COPD exacerbation and 41 healthy subjects. In patients all parameters were assessed at two time points: Firstly, one day after admission and secondly, after 7 10 days when they were clinically stable enough to be discharged. Patients were divided in two groups according the presence of ischemic heart disease (IHD): IHD positive (IHD+) patients and IHD negative (IHD-) patients. METHODS AND RESULTS During hospitalisation O2•-, malondialdehyde (MDA), advanced oxidation protein products (AOPP) and total oxidant status (TOS) increased and were higher at discharge compared with admission and the control group. Superoxide dismutase (SOD) activity was significantly lower in COPD patients at both time points compared with the control group. Total antioxidant status (TAS) was significantly lower and the prooxidant-antioxidant balance (PAB) was higher at both time points in COPD patients compared with the control group. High sensitive C-reactive protein (hsCRP) and also the neutrophil count were significantly higher at admission compared with discharge. Paraoxonase 1 (PON1) enzymatic activities in COPD patients did not differ compared with the control group. IHD+ COPD patients had significantly lower PON1 activity but higher PAB levels and hsCRP concentrations, compared with IHD COPD patients. CONCLUSION The oxidant/antioxidant imbalance was significantly pronounced in patients with COPD exacerbation for at least 24 hours following their admission and when they were clinically stable enough to be discharged. Increased oxidative stress, elevated systemic inflammation and decreased antioxidant defence were common in end-stage disease and particularly COPD patients with ischemic heart disease.

Glutathione S-transferase A1, M1, P1 and T1 null or low-activity genotypes are associated with enhanced oxidative damage among haemodialysis patients

BACKGROUND Increased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S-transferases (GST) are involved in the detoxification of xenobiotics and protection of oxidative damage. We hypothesized that genetic polymorphism in antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 is more frequent in ESRD and modulates the degree of oxidative stress in these patients. METHODS GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 ESRD patients and 199 age- and gender-matched controls. Markers of protein and lipid oxidative damage [thiol groups, carbonyl groups, advanced oxidative protein products, nitrotyrosine, malondialdehyde (MDA) and MDA adducts], together with total oxidant status and pro-oxidant-antioxidant balance were determined. RESULTS Individual GST polymorphisms influence vulnerability to both protein and lipid oxidation, with GSTM1-null gene variant having the most pronounced effect. Furthermore, a strong combined effect of null/low-activity GSTM1, GSTT1, GSTA1 and GSTP1 genotypes in terms of susceptibility towards oxidative and carbonyl stress was found in ESRD patients. When patients were stratified according to GSTM1 and GSTT1, the highest oxidant damage was noted in those with the GSTM1-null/GSTT1-null genotype. The observed effect was even stronger in patients with the third low-activity GSTP1 or GSTA1 genotype. Finally, the level of oxidative and carbonyl stress was most pronounced in the subgroup of patients with all four null or low-activity GSTM1, GSTT1, GSTP1 and GSTA1 genotypes. CONCLUSIONS According to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment.

Biomarkers of acute kidney injury in pediatric cardiac surgery

OBJECTIVES Acute kidney injury (AKI) is a significant problem in children undergoing cardiopulmonary bypass (CPB). The aims of this study were to assess the diagnostic validity of serum CysC (sCysC), serum neutrophil gelatinase lipocalin (sNGAL), urine neutrophil gelatinase lipocalin (uNGAL), urine kidney injury molecule (uKIM)-1, and urine liver fatty acid-binding protein (uL-FABP) to predict AKI presence and severity in children undergoing CPB. DESIGN AND METHODS We performed a prospective single-center evaluation of sCysC, sNGAL, uNGAL, uKIM-1 and uL-FABP at 0, 2, 6, 24 and 48 h postoperatively in children undergoing CPB during cardiac surgery. AKI was defined as ≥25% decrease in the estimated creatinine clearance (eCCl) from pre-operative baseline at 48h after surgery. RESULTS Of the 112 patients, 18 patients (16.1%) developed AKI; four of them needed acute dialysis treatment and three AKI patients died. In the AKI compared to the non-AKI group, sCysC at 2h, and uNGAL and uL-FABP at 2-48 h were significantly increased, as well as CPB, aortic cross clamp time and length of hospital stay. Biomarkers increased with worsening AKI severity. At 2h after CPB the best accuracy for diagnosis of AKI had uL-FABP and sCysC with area under the receiver operator curve (AUC) of 0.89 and 0.73, respectively. At 6 and 24h after CPB the best AUC was found for uL-FABP (0.75 and 0.87 respectively) and for uNGAL (0.70 and 0.93, respectively). CONCLUSIONS sCysC, uNGAL and uL-FABP are reliable early predictors for AKI after CPB. By allowing earlier timing of injury and earlier intervention, they could improve AKI outcome.

Route-dependent effects of cadmium/cadmium and magnesium acute treatment on parameters of oxidative stress in rat liver

The study was designed to evaluate and compare the effects of single oral (or) and intraperitoneal (i.p.) cadmium (Cd) administration on parameters of oxidative stress in liver of rats. Furthermore, investigation on protective effects of magnesium (Mg) or and i.p. pretreatment on the same parameters was performed. Wistar rats were administrated oral dose of Cd (30 mg Cd/kg b.w.)/Cd+Mg (30 mg Cd/kg b.w., 50 mg Mg/kg b.w.) or i.p. dose of Cd (1.5 mg Cd/kg b.w.)/Cd+Mg (1.5 mg Cd/kg b.w., 3 mg Mg/kg b.w.) and sacrificed after 24 h. In liver homogenates superoxide anion, malondialdehyde, non-protein sulfhydryl groups, total sulfhydryl groups content, and superoxide dismutase activity were determined. Cadmium intoxication caused the increase of superoxide anion and malondialdehyde levels and had negative effect on investigated parameters of antioxidant defense system, except on total sulfhydryl groups. The negative effect was more emphasized after i.p. Cd administration. Oral Mg pretreatment induced more pronounced positive effect than Mg given intraperitoneally that can be attributed, at least partly, to Cd and Mg interactions on the level of GIT. On the basis of the obtained results it can be concluded that both Cd and Cd+Mg effects on parameters of oxidative stress in rats liver are route-dependent.

Relationship between bone resorption, oxidative stress and inflammation in severe COPD exacerbation.

BACKGROUND The natural course of chronic obstructive pulmonary disease (COPD) is complicated by the development of systemic consequences and co-morbidities. Increasing evidence indicates that COPD and osteoporosis are strongly linked. The common features in COPD pathology, history of smoking, age, inactivity, systemic inflammation, and use of systemic corticosteroids, are important risk factors for osteoporosis. METHODS Pulmonary function, matrix metalloproteinase, tissue inhibitor of metalloproteinases, oxidative stress parameters, inflammatory markers and bone resorption marker were measured in 85 COPD patients and 47 healthy subjects. In patients, all parameters were assessed at two time points: one day after admission during exacerbation and about 30 days after, in the stable state of disease. RESULTS In patients, bone resorption marker collagen type I β-isomerized C-terminal telopeptide (beta CL) was increased during exacerbation: geometric mean 0.521, compared with stable patients 0.408, p<0.01, and control subjects 0.362 ng/ml, p<0.001. During exacerbation high sensitivity C-reactive protein (hsCRP) and neutrophil count were significantly higher in COPD patients compared with the control group, p<0.001. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations were significantly higher in COPD patients, stable state or exacerbation, compared with control subjects, p<0.001. In patients during exacerbation, total oxidative status (TOS) was higher compared with the stable state, p<0.05 and control group, p<0.001. Multiple linear regression for the joint influence of inflammation, hypoxia and oxidative status during exacerbation showed almost 60% influence on the variability of beta CL concentrations. CONCLUSION Intensification of disease characteristic symptoms such as inflammation, hypoxia, protease/antiprotease imbalance and oxidative stress, during exacerbation episodes in COPD patients may also contribute to increased bone resorption.

Total bilirubin in young men and women: Association with risk markers for cardiovascular diseases

OBJECTIVE The aim of this study was to investigate whether high bilirubin concentration is a protective factor in cardiovascular disease (CAD) and how it correlates with parameters of oxidative stress in young males and females. METHODS The study comprised 628 healthy subjects of both genders, 18-22years of age. In fasting sera the concentration of total bilirubin (Tbil), parameters of cardiovascular risk and oxidative stress were determined. The results were analyzed by appropriate statistical methods. RESULTS We found no gender differences in body mass index (BMI), blood pressure and lipid profile between subjects with low and high Tbil level. Men with high Tbil had higher concentrations of albumin and uric acid (p<0.001) and lower of oxLDL (<0.05), while women had higher albumin (p<0.05) and lower TBARS (p<0.05). Significant positive correlation in men was found between Tbil, uric acid and albumin, while for glucose and TBARS this association was negative. In female significant positive correlation was between Tbil, HDL-C, fibrinogen, albumin and uric acid and negative between Tbil and TBARS. The high concentration of Tbil in men was independently associated with uric acid (p<0.05) and oxLDL (p<0.001), while in women it was independently associated with TBARS (p<0.05). After adjustment for traditional lipid parameters the predictive power of high bilirubin in men remained for uric acid (p<0.001) and TBARS in women (p<0.05). CONCLUSION These findings jointly support the concept that bilirubin via its antioxidant potential has a protective effect against cardiovascular disease in young male and female.

Dyslipidemia and oxidative stress in sarcoidosis patients

OBJECTIVES Sarcoidosis is an inflammatory disease characterised by enhanced production of reactive oxygen species and alterations in the circulating lipid profile. Both attributes are thought to play a role in its pathogenesis. However, current knowledge regarding the significance of blood oxidative stress/anti-oxidant defence as well as alterations in lipid status parameters in sarcoidosis is scarce. The aim of our study was to assess these parameters and their inter-relationships, as well as their potential for patient-control discrimination. DESIGN AND METHODS Oxidative stress status and anti-oxidant defence parameters were determined in serum and erythrocytes and lipid status parameters were assessed in the serum of 213 treated sarcoidosis patients and 90 controls. RESULTS Malondialdehyde, superoxide anion, total oxidant status, prooxidant-antioxidant balance and triglycerides were significantly higher whereas total anti-oxidant status, superoxide dismutase activity and HDL-cholesterol were significantly lower in sarcoidosis patients compared with controls. Total sulfhydryl group content was higher in patients compared with controls. Serum and erythrocyte malondialdehyde exhibited the strongest ability to predict disease presence. Elevated oxidative stress was characterised by higher clinical accuracy compared with lipid status abnormality. Some oxidative stress and lipid status markers were significantly associated in sarcoidosis. CONCLUSIONS Sarcoidosis is characterised by increased oxidative stress, diminished overall anti-oxidative protection and alterations in the circulating lipid profile. Both oxidative stress and lipid status parameters demonstrated the potential to discriminate sarcoidosis from controls which was particularly evident from the point of view of oxidative stress status parameters. Association between these parameters may indicate an increased risk for atherosclerosis development.

Association of serum amyloid A and oxidative stress with paraoxonase 1 in sarcoidosis patients

It has been reported that high‐density lipoprotein (HDL) particles have anti‐inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis.

Prooxidant-antioxidant balance, hsTnI and hsCRP: mortality prediction in haemodialysis patients, two-year follow-up.

Abstract Oxidative stress and inflammation are highly intertwined pathophysiological processes. We analyzed the markers of these processes and high-sensitive troponin I (hsTnI) for mortality prediction in patients on haemodialysis. This study enrolled a total of 62 patients on regular haemodialysis. The patients were monitored for two years, and the observed outcomes were all-cause and cardiovascular mortality. Blood samples were taken before one dialysis session for analysis of the baseline concentrations of prooxidant–antioxidant balance (PAB), total antioxidant status (TAS), total oxidative status (TOS), hsTnI, hsCRP and resistin. The overall all-cause mortality was 37.1% and CVD mortality 16.1%. By univariate and multivariate logistic regression, our findings suggest that good predictors of all-cause mortality include hsCRP and PAB (p < .05) and of CVD mortality hsCRP (p < .05) and hsTnI (p < .001). To evaluate the relationship between the combined parameter measurements and all-cause/CVD mortality risk, patients were divided into three groups according to their PAB, hsCRP and hsTnI concentrations. The cutoffs for hsCRP and hsTnI and the median for PAB were used. Kaplan–Meier survival curves pointed out that the highest mortality risk of all-cause mortality was in the group with hsCRP levels above the cutoff and PAB levels above the median (p < .001). The highest risk of CVD mortality was found in the group with hsCRP and hsTnI levels above the cutoff levels (p = .001). Our data suggest that hsCRP and PAB are very good predictors of all-cause mortality. For CVD complications and mortality prediction in HD patients, the most sensitive parameters appear to be hsTnI and hsCRP.

Associations of oxidative stress status parameters with traditional cardiovascular disease risk factors in patients with schizophrenia

Abstract Background. The purpose of this study was to assess oxidative stress status parameters and their possible associations with traditional cardiovascular risk factors in patients with schizophrenia, as well as their potential for patient-control discrimination. Methods. Fasting glucose, lipid profile and oxidative stress status parameters were assessed in 30 schizophrenic patients with atypical antipsychotic therapy and 60 control subjects. Results. Malondialdehyde (MDA), pro-oxidant/antioxidant balance (PAB) and total anti-oxidant status (TAS) were significantly higher whereas total sulfhydryl (SH) groups were significantly lower in schizophrenic patients vs. control group. Higher serum PAB values showed an independent association with schizophrenia. The addition of PAB to conventional risk factors improved discrimination between healthy control subjects and patients. Conclusion. Increased oxidative stress and changed lipid profile parameters are associated in schizophrenic patients and may indicate risk for atherosclerosis. The serum PAB level may reflect the levels of oxidative stress in schizophrenia and improve discrimination of patients from controls.