Markers of Oxidative Stress and Endothelial Dysfunction Predict Haemodialysis Patients Survival.

INTRODUCTION: Overall survival of patients with end-stage renal disease (ESRD) remains poor. Oxidative stress is one of the major risk factors associated with mortality in this patient group. As glutathione S-transferases (GST) are well-established antioxidants, we hypothesized that a model including GST gene polymorphisms, oxidative damage byproducts and cell adhesion markers has a prognostic role in ESRD patient survival. METHODS: A prospective study of 199 patients with ESRD on haemodialysis was conducted. GST genotype, oxidative stress byproducts and cell adhesion molecules were measured in plasma. Multivariate Cox regression and Kaplan-Meier survival analyses were performed to test the predictive ability of these parameters in the 8-year follow-up period. RESULTS: GSTM1-null genotype was associated with significantly shorter overall (HR 1.6, p = 0.018) and cardiovascular-specific (HR 2.1, p = 0.010) survival. Oxidative stress byproducts (advanced oxidation protein products [AOPP], prooxidant-antioxidant balance [PAB], malondialdehyde [MDA]) and cell adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1] and soluble intercellular adhesion molecule-1 [sICAM-1]) demonstrated a significant predictive role in terms of overall and cardiovascular survival. When 6 biomarkers (GSTM1 genotype, high AOPP/PAB/MDA/-sVCAM-1/sICAM-1) were combined into a scoring model, a significantly shorter overall and cardiovascular survival was observed for patients with the highest score (p < 0.001). CONCLUSION: We identified a novel panel of biomarkers that can be utilized in predicting survival in ESRD patients. This biomarker signature could enable better monitoring of patients and stratification into appropriate treatment groups.

The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet.

CONTEXT: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. OBJECTIVES: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. MATERIALS AND METHODS: Eighteen male Wistar albino rats were divided into three groups (n = 6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. RESULTS: Normalized HO-1 [0.11 (0.04-0.24)] and MCP-1 [0.29 (0.21-0.47)] mRNA levels and DNA scores [12.50 (4.50-36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35-2.51)], p = 0.021 for HO-1 [0.85 (0.61-3.45)], p = 0.047 for MCP-1 and [176.5 (66.50-221.25)], p = 0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21-0.71), p = 0.049]. CONCLUSIONS: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage.

PRO-OXIDANTS AND ANTIOXIDANTS IN RETINOPATHY OF PREMATURITY.

- Premature infants are susceptible to oxidative stress that causes neonatal disease such as retinopathy of prematurity (ROP). Oxidative stress is an imbalance between the production of pro-oxidants and the ability of the body to detoxify their harmful effects by antioxidants. The proliferative phase 2 ROP occurs at around 33rd postmenstrual week (pmw). The purpose of our study was to evaluate the pro-oxidant/antioxidant status in preterm infants at 33rd pmw. The study included 59 premature infants. ROP was classified according to the International Classification of Retinopathy of Prematurity. Total oxidative status (TOS), total antioxidant status (TAS), malondialdehyde (MDA) and paraoxonase 1 (PON1) activity were determined spectrophotometrically. The values of the pro-oxidants TOS and MDA were significantly higher in infants with ROP as compared to infants without ROP (p<0.05 both). There were no significant differences in the values of TAS and PON1 between the infants with and without ROP. According to study results, TOS and MDA are good markers of oxidative stress, whereas TAS and PON1 activity are unreliable in assessing antioxidant protection.

Association of adenylate cyclase-associated protein 1 with coronary artery disease.

BACKGROUND: Adenylate cyclase-associated protein 1 (CAP1) is a recently identified receptor for human resistin. As resistin has been related to CAD development and progression and CAP1 has never been evaluated in CAD, the aim of this study was to determine its peripheral blood mononuclear cells (PBMCs) mRNA in patients with CAD, and resistin plasma concentration, PBMCs resistin and CD36 mRNA, considering resistiǹs ability to stimulate CD36 expression in vitro. MATERIALS AND METHODS: This case-controlled study included 27 healthy subjects (CG) and 66 patients requiring coronary angiography. Of the latter, 42 had nonsignificant CAD whereas 24 had significant CAD. Circulating resistin was measured by ELISA; PBMCs CAP1, resistin and CD36 mRNA were determined by real-time PCR. RESULTS: Patients with significant as well as patients with nonsignificant CAD had significantly higher resistin concentrations compared to the CG (P < 0·001; P = 0·003). Resistin mRNA did not show significant difference between the investigated groups. CAP1 and CD36 mRNA were significantly higher in significant CAD (P < 0·001; P < 0·001, respectively) and nonsignificant CAD (P < 0·001; P < 0·001, respectively) compared to the CG; significant CAD showed significantly higher CD36 mRNA (P = 0·040) compared to the nonsignificant CAD group. Multiple linear regression analysis identified Tg and CD36 mRNA as independent predictors of CAP1 (R2  = 0·402; adjR2  = 0·376). CONCLUSION: Significant up-regulation of PBMCs CAP1, CD36 mRNA and plasma resistin found in significant CAD, as well as in nonsignificant CAD compared to CG, indicates that resistin could be able to exert its effects stronger on cells with up-regulated CAP1 mRNA thus contributing atherosclerosis development.

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

BACKGROUND: Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. METHODS: The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. RESULTS: In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and ß-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). CONCLUSIONS: The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/ß-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

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

BACKGROUND: 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. MATERIALS AND METHODS: Inflammatory [high-sensitive C-reactive protein (hsCRP), angiotensin-converting enzyme (ACE), SAA], lipid [total cholesterol (TC), HDL-cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG)] oxidative stress status parameters [total oxidant status (TOS), malondialdehyde (MDA), pro-oxidant-antioxidant balance (PAB), sulfhydryl (SH) groups] and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects. RESULTS: HsCRP (P < 0·05), TC, LDL-c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL-c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration. CONCLUSIONS: We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.

Higher circulating resistin protein and PBMCs resistin mRNA levels are associated with increased prevalence of small dense LDL particles in coronary artery disease patients.

Recent in vitro experiments have indicated that human resistin increases the number of lipoprotein particles secreted by the human hepatocytes and also influences their quality, in terms of generating more proatherogenic lipid particles. The aim of this study is to investigate associations of plasma resistin and peripheral blood mononuclear cells (PBMCs) resistin messenger RNA (mRNA) levels with different prevalence of small, dense low-density lipoprotein particles (sdLDL) in patients with indications for coronary angiography. This study included 65 patients requiring coronary angiography. There were 41 patients without significant stenosis and 24 patients with significant stenosis in at least one major coronary artery. Circulating resistin was measured by enzyme-linked immunosorbent assay; PBMC resistin mRNA was determined by real-time polymerase chain reaction. The LDL and high density lipoprotein subclasses were determined by gradient gel electrophoresis. Plasma resistin (P = 0.031) and PBMCs resistin mRNA (P = 0.004) were significantly higher in patients with proportion of sdLDL particles ≥ 50%, compared to the group with relative proportion of sdLDL particles < 50%. Plasma resistin correlated positively with creatinine (r = 0.456, P < 0.001) and resistin mRNA (r = 0.298, P = 0.014) but negatively with body mass index (r = -0.254, P = 0.034) and total cholesterol (r = -0.286, P = 0.021). Multiple linear regression analysis revealed LDL particle diameter as the only independent predictor of resistin mRNA (R(2) = 0.258; adjR(2) = 0.190). A significant association between resistin, both PBMCs mRNA and plasma protein, and the relative proportion of sdLDL particles in the circulation of coronary artery disease patients has been established, which implies that increased gene expression of resistin in PBMCs and higher resistin concentration in plasma are related to pro-atherogenic LDL particle phenotype.

Hypertension, lipoprotein subclasses and lipid transfer proteins in obese children and adolescents.

BACKGROUND: Obesity-related childhood hypertension is associated with disturbances of serum lipids, but less is known about distribution of lipoprotein subclasses and activities of proteins involved in reverse cholesterol transport in hypertensive obese children. Our objective was to determine low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses distribution and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in hypertensive and non-hypertensive obese children. METHODS: A total of 40 hypertensive and 25 non-hypertensive obese children were enrolled. Lipoprotein subclasses were assessed by polyacrylamide gradient gel electrophoresis. LCAT and CETP activities were determined as a rate of formation and a rate of transfer of cholesteryl esters. RESULTS: Despite of comparable values of serum lipid parameters, a shift toward smaller LDL and HDL subclasses was observed in hypertensive compared to normotensive obese children. Activities of LCAT were similar, but proatherogenic CETP activities were significantly higher in the hypertensive group (p = 0.036). LCAT/net CETP ratio inversely correlated with relative proportion of small, dense LDL particles (ρ = -0.423; p = 0.025) in the group with hypertension. CONCLUSIONS: The results of our study demonstrated a tendency toward altered distribution of lipoprotein subclasses in favor of more proatherogenic particles in childhood hypertension. Also, hypertensive obese children had increased proatherogenic CETP activity.

Gestational diabetes mellitus modulates neonatal high-density lipoprotein composition and its functional heterogeneity.

Gestational diabetes mellitus (GDM) is related to neonatal macrosomia and an increased risk of vascular events. We hypothesized that GDM exerts qualitative effects on neonatal high-density lipoprotein (HDL). HDL was isolated from control (n=11) and GDM maternal/neonatal donors (n=9) and subjected to shotgun proteomics. Differences in HDL mobility were assessed by FPLC and native gel-electrophoresis. Paraoxonase (PON1) activity, cholesterol ester-transfer protein (CETP) mass and activity, phospholipid, triglyceride and cholesterol concentrations were quantified with commercial kits. Total anti-oxidative capacity and cholesterol efflux capability of HDLs were measured. Four proteins involved in lipid metabolism, inflammation and innate immunity were differentially expressed between controls and GDM neonates. ApoM (decreased, p<0.05) and SAA1 (increased, p<0.05) showed the same differences on both, maternal and neonatal GDM HDL. Lower PON1 protein expression was corroborated by lower activity (p<0.05) which in turn was associated with attenuated anti-oxidant capacity of GDM HDL. Protein changes were accompanied by increased levels of triglycerides and decreased levels of cholesterol esters, respectively. The observed differences in GDM HDL lipid moiety may be related to CETP mass and activity alterations. The rate of cholesterol efflux from term trophoblasts to maternal and from placental endothelial cells to neonatal GDM HDL was impaired (p<0.05). In conclusion, GDM causes changes in HDL composition and is intimately associated with impaired cholesterol efflux capability as well as diminished anti-oxidative particle properties. Remodeling of neonatal GDM HDL in utero supports the hypothesis that maternal conditions in pregnancy impact neonatal lipoprotein metabolism.

Are decreased AdipoR1 mRNA levels associated with adiponectin resistance in coronary artery disease patients?

The aim of the present study was to investigate if circulating adiponectin levels and the expression of AdipoR1 and AdipoR2 in peripheral blood mononuclear cells (PBMC) are altered in coronary artery disease (CAD) patients, with and without significant stenosis, compared to healthy patients. The present study included 69 patients with presenting symptoms of CAD (26 patients with significant stenosis and 43 patients without significant stenosis). The control group (CG) consisted of 33 healthy patients. Circulating adiponectin levels were measured by enzyme-linked immunosorbent assay, whereas AdipoR1 and AdipoR2 mRNA levels in PBMC were determined by real-time polymerase chain reaction. Adiponectin levels were significantly higher in patients with and without significant stenosis compared to the CG (P < 0.001 vs P = 0.006, respectively). Both patient groups had lower AdipoR1 levels compared to the CG (P < 0.001 vs P < 0.001, respectively). There were no significant differences in these parameters between the two patient groups. Adiponectin negatively correlated with body mass index, triglycerides, insulin and homeostasis model assessment of insulin resistance index (HOMA IR), and positively with high-denisty lipoprotein cholesterol in the CG. Glucose, insulin, and the HOMA IR index negatively correlated with adiponectin in patients. A positive correlation between adiponectin receptors was found in patients and the CG. Decreased AdipoR1 mRNA levels and increased circulating adiponectin in advanced stages of CAD, as well as in patients without significant stenosis, compared to the CG, implies that CAD could be related to 'adiponectin resistance'. Despite increased adiponectin, its protective effects could be diminished even in early stages of atherosclerosis.

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury.

Sepsis-associated acute kidney injury (SA-AKI) severely impacts morbidity and mortality in surgical patients with sepsis. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) have an important role in pathophysiology of sepsis but they have been unexplored in SA-AKI. We aimed to investigate the role of MMP-9 and TIMP-1 in septic surgical patients with SA-AKI and to evaluate them as diagnostic biomarkers of SA-AKI. This prospective observational study compared 53 major abdominal surgery patients with sepsis divided into SA-AKI (n = 37) and non-SA-AKI (n =16) group to 50 controls without sepsis matched by age, gender, comorbidities and type of surgery. Blood and urine samples from septic patients were collected on admission to ICU and 24, 48, 72 and 96 h later and once from the controls. The levels of MMP-9, TIMP-1, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, urea and creatinine were measured. MMP-9/TIMP-1 ratio and disease severity scores, such as Sequential Organ Failure Assessment (SOFA), were calculated. Septic patients with SA-AKI had higher serum TIMP-1 levels and lower serum MMP-9 levels and lower MMP-9/TIMP ratio, compared to septic patients without SA-AKI and controls. The levels of these biomarkers did not change significantly over time. MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio correlated with urea, creatinine, NGAL, and SOFA scores. Moreover, using the area under ROC curve, we showed that TIMP-1 and MMP-9/TIMP-1 ratio, but not MMP-9, were good diagnostic biomarkers of SA-AKI. We report for the first time the potential diagnostic value of TIMP-1 and MMP-9/TIMP-1 ratio in SA-AKI.

Association of small, dense low-density lipoprotein cholesterol and galectin-3 in patients with chronic kidney disease.

BACKGROUND: Dyslipidemia is a common feature of chronic kidney disease (CKD). Although it has been observed that the pattern of lipid abnormalities can vary according to the stage of CKD, there is lack of data concerning the distribution of lipoprotein subclasses at various stages of the disease. In addition, association of proatherogenic small, dense low-density lipoprotein (sdLDL) subclasses with markers of inflammation, such is galectin-3, is not sufficiently explored. The aim of this study was to analyze concentrations and relative proportions of sdLDL-cholesterol (sdLDL-C) and galectin-3 in patients with CKD, with respect to the stage of the disease. Also, we sought possible independent associations of galectin-3 and sdLDL-C. METHODS: The study involved 100 hemodialysis (HD) and 50 pre-dialysis patients, together with 94 healthy individuals. SdLDL-C was measured by heparin-magnesium precipitation method. Galectin-3 was measured by ELISA technique. RESULTS: Galectin-3 levels were higher in pre-dialysis and HD patients than in the control group (p < 0.01). The concentration of sdLDL-C was highest in the pre-dialysis group and lowest in HD patients (p < 0.01). CKD patients with increased galectin-3 concentrations had significantly higher relative proportions of cholesterol in sdLDL (% sdLDL-C) than their counterparts with lower galectin-3 levels (p < 0.05). Relative proportion of sdLDL-C was shown to be an independent determinant of galectin-3 concentration. CONCLUSIONS: Our results demonstrated alterations in concentrations and proportions of sdLDL-C according to the stages of CKD. The observed independent associations of % sdLDL-C and galectin-3 provide further insight into their complex interaction during the progression of atherosclerosis in CKD.

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.

Hyperlipidemia, oxidative stress, and intima media thickness in children with chronic kidney disease.

BACKGROUND: The roles of dyslipidemia and oxidative stress in the early phases of atherosclerosis were tested in children with chronic kidney disease (CKD). Intima media thickness of common carotid arteries (cIMT) is used as a measure of early atherosclerosis. METHODS: Fifty-two pediatric CKD patients were enrolled in the study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20 with chronic hemodialysis (cHD) patients, and 36 healthy children (control group, CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were assessed. cIMT was measured by ultrasound, adjusted for age and sex, and presented as standard deviation scores (SDS). RESULTS: Children with CKD had disturbed lipid content, which was most pronounced in cHD children, with higher free cholesterol and triglycerides compared with healthy children. Oxidative stress was markedly increased (malodialdehyde [MDA, µmol/L]: CRF 1.50 ± 0.26, RT 1.55 ± 0.40, cHD 1.77 ± 0.34, CG 0.97 ± 0.33, p < 0.001) and antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120 ± 21, CRF 84 ± 25, RT 93 ± 12, cHD 119 ± 37, p < 0.001). Multiple linear regression analysis showed that a model that included disease duration, blood pressure, urea, lipid, and oxidative status parameters accounted for more than 90% of the variability of cIMT-SDS. CONCLUSIONS: Early atherosclerosis in CKD children is caused, at least in part, by dyslipidemia and oxidative stress. Monitoring of vessel wall changes, along with assessment of oxidative stress status and high density lipoprotein (HDL) functionality is necessary to ensure better therapeutic strategies for delaying atherosclerotic changes in their asymptomatic phase.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

BACKGROUND: The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. METHODS: We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. RESULTS: Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. CONCLUSIONS: NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor.

Changes in LDL and HDL subclasses in normal pregnancy and associations with birth weight, birth length and head circumference.

Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P < 0.001), due to reduction in relative proportion of LDL I (P < 0.01) and increase of LDL II (P < 0.001) and IIIA (P < 0.05) subclasses. In the same time, HDL size and proportions of HDL 2a particles significantly decreased (P < 0.001), with concomitant increase of HDL 3b and 3c subclasses (P < 0.05). Observed alterations were associated with changes in serum triglyceride levels. Rearrangement in LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.

Effect of astaxanthin supplementation on paraoxonase 1 activities and oxidative stress status in young soccer players.

The purpose of the study was to examine the effects of astaxanthin (Asx) on paraoxonase (PON1) activities and oxidative stress status in soccer players. Forty soccer players were randomly assigned in a double-blind fashion to Asx and placebo (P) group. Blood samples were obtained before, 45 and 90 days after supplementation. PON1 activity was assessed by using two substrates: paraoxon and diazoxon. The oxidative stress biomarkers were also examined: total sulphydryl group content (-SH groups), thiobarbituric acid-reactive substances (TBARS), advanced oxidation protein products and redox balance. The significant interaction effect of supplementation and training (p < 0.05) on PON1 activity toward paraoxon was observed. The PON1 activity toward diazoxon increased in Asx group after 90 days (p < 0.01), while there was no significant difference in P group. SH groups content rose from pre- to post-supplementation period only in Asx group (supplementation and training, p < 0.05; training, p < 0.01). TBARS levels decreased after 45 days and increased after 90 days of regular soccer training in both groups (training, p < 0.001). Redox balance decreased significantly in response to the regular training, regardless of treatment group (training, p < 0.001). Asx supplementation might increase total SH groups content and improve PON1 activity through protection of free thiol groups against oxidative modification.

Association of the atherogenic index of plasma and oxidative stress status with weight gain during non-complicated pregnancy.

BACKGROUND: Pregnancy is a stressful condition linked with altered lipid profile, increased oxidative stress and increased inflammation processes. The purpose of the present study was to determine the associations between those alterations with increased weight gain during pregnancy. METHODS: The atherogenic index of plasma (AIP) and oxidative stress status parameters were determinated in 50 healthy and 172 pregnant women with non-complicated pregnancy. Pregnant women were divided in four groups according to body mass index (BMI) values (BMI quartiles). RESULTS: Oxidative stress parameters were significantly lower in the control group compared with all the pregnant women quartiles. Unexpectedly, differences in oxidative stress parameters between BMI quartiles groups were not significant. The antioxidant defence parameters remained quite similar in the different BMI quartiles. Weight gain and paraoxonase-1 (PON1) activities were independently associated with increased AIP while weight gain and triglyceride concentration were found to be significant predictors of PON1 activities. CONCLUSIONS: The results of our current study indicate the association of maternal weight gain during pregnancy and altered lipid profile, elevated oxidative stress and changed antioxidative capacity of PON1. Taken together all these facts indicate possible increased risk of cardiovascular disease (CVD) development in later life if the weight gain during pregnancy is excessive.

Can non-cholesterol sterols indicate the presence of specific dysregulation of cholesterol metabolism in patients with colorectal cancer?

Colorectal cancer (CRC) is a highly prevalent malignancy. Previous studies suggested that cholesterol might play a signficant role in malignant transformation and proliferation. Non-cholesterol sterols (NCS), which are transported by serum lipoproteins alongside cholesterol, are regarded as cholesterol synthesis and absorption markers. Quantification of NCS in serum and HDL fraction (NCSHDL), could provide a better insight into the cholesterol metabolism. The aim of this study was to examine the status of cholesterol synthesis and cholesterol absorption markers in serum and HDL fraction and explore their interrelation in CRC patients. Current study was designed as observational, case-control study. The study included 73 CRC patients and 95 healthy subjects. NCS and NCSHDL concentrations were determined by HPLC-MS/MS. Based on NCS and NCSHDL concentrations, different cholesterol homeostasis indices were calculated. Patients had significantly lower NCS (P<0.001) and NCSHDL concentrations (P<0.001 for desmosterolHDL; P<0.05 for lathosterolHDL, P=0.001 for campesterolHDL, P<0.001 for ß-sitosterolHDL). NCSHDL/NCS (P<0.005 for desmosterolHDL/desmosterol; P<0.05 for lathosterolHDL/lathosterol; P<0.001 for both ß-sitosterolHDL/ß-sitosterol and campesterolHDL/campesterol) and synthesis to absorption ratio (CSI/CAI) (P<0.005) were increased in CRC patients. Additionally, low serum concentrations of desmosterol (P<0.001; OR=0.329; 95%CI (0.199-0.542)) and campesterol (P<0.001; OR=0.540; 95%CI (0.424-0.687)) were independent predictors of CRC presence. Our data suggest that cholesterol homeostasis in CRC is shifted towards increased synthesis. Relative abundance of NCS in HDL particles is increased, suggesting the possible overproduction of cholesterol precursors in peripheral tissues.

Characteristics of low-density and high-density lipoprotein subclasses in pediatric renal transplant recipients.

Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles and their associations with carotid intima-media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)-cholesterol (sdLDL-C) and sdLDL-apolipoprotein B (sdLDL-apoB) using heparin-magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P < 0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL-C (P < 0.01) and sdLDL-apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P < 0.05). Patients treated with cyclosporine had significantly higher sdLDL-C and sdLDL-apoB concentrations (P < 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small-sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy.