Lipid peroxidation as risk factor for endothelial dysfunction in antiphospholipid syndrome patients.

The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616-0.837 and AUC 0.824, p˂0.001, 95 % CI 0.690-0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients.

Methylmalonic acid and neutrophil morphometric index in laboratory diagnosis of cobalamin deficiency without macrocytosis.

INTRODUCTION: This study aimed to investigate the utility of methylmalonic acid (MMA) and neutrophil Cell Population Data, available on the Beckman Coulter LH750 Analyser (Miami, FL, USA), in laboratory assessment of cobalamin status in patients at risk of cobalamin deficiency, without macrocytosis and inflammation. METHODS: The study group included 189 patients. Neutrophil Cell Population Data along with vitamin B12 and homocysteine were assessed in regard to MMA tertile groups. RESULTS: Statistically significant differences were between lower and upper MMA tertile in serum B12 (P ˂ 0.001), homocysteine (P = 0.001) and neutrophil morphometric index, NeS-DW (P = 0.029). Also, serum B12 concentrations were significantly different between lower and middle MMA tertile, P = 0.005. Receiver operating characteristic analysis of NeS-DW ability to detect MMA˃367 nmol/L revealed a significant area under the curve AUC = 0.761 P ˂ 0.001 95% CI 0.693-0.830. Optimal cut-off value was NeS-DW˃3.51% with sensitivity of 74.19% and specificity of 68.87%. CONCLUSION: In patients at risk of cobalamin deficiency and normal MCV, classification according to MMA revealed cobalamin status differences. Neutrophil morphometric index may be an indicator of early changes in neutrophil nucleus morphology caused by impaired cobalamin status.

Early detection of iron deficiency in elite athletes: could microcytic anemia factor (Maf) be useful?

INTRODUCTION: The aim of this study was to establish the sensitivity and specificity of the microcytic anemia factor (Maf(®)), which is generated by the Coulter LH 750 analyzer in the evaluation of iron depletion and iron-deficient erythropoiesis in athletes. METHODS: A total of 142 athletes were divided into three groups: with iron depletion, with iron-deficient erythropoiesis, and controls. The following parameters were measured: RBCs (red blood cells), Hb (hemoglobin), Hct (hematocrit), MCV (mean cellular volume), MCH (mean cell hemoglobin), MCHC (mean cell hemoglobin corpuscular), RDW (red cell distribution width), Maf(®), Reticulocytes, Ferritin, sTfR (soluble transferrin receptor), Transferrin, Haptoglobin, IL- 6 (Interleukin-6), hs-CRP (high-sensitivity C-reactive protein). RESULTS: The best Maf(®) value to exclude iron depletion in athletes was 130.3, showing a sensitivity of 72.6% and a specificity of 57.3%. The AUC was 0.690 (CI 95% 0.607-0.765, P < 0.001). ROC curve analysis for Maf(®) in the diagnosis of iron-deficient erythropoiesis indicates sensitivity of 61.5%, and specificity of 93.0%, with AUC = 0.826 (CI 95% 0.754-0.885, P < 0.001) and on cutoff value 114. CONCLUSIONS: This study shows that Maf(®) generated by the Coulter LH 700 Series hematology analyzers, performs very well in discriminating healthy athletes and those with different stages of iron deficiency. Also, in cost/benefit terms, monitoring of Maf(®) is justified as a low cost, effective screening parameter for determining iron status in athletes.

Evaluation of derived Coulter red blood cell parameters for the assessment of iron deficiency in adults with congenital heart disease.

INTRODUCTION: The aim of our study was to evaluate derived red blood cell parameters in determining the presence of iron depletion and iron-deficient erythropoiesis, as states that precede iron deficiency anemia, in adults with congenital heart disease. METHODS: Eighty-eight adults who were diagnosed with congenital heart disease were divided into two groups (cyanotic and acyanotic). In both groups, congenital heart disease patients were then divided into three subgroups: with iron depletion, with iron-deficient erythropoiesis, and a control group. The following parameters were measured: complete blood count, reticulocytes, ferritin, soluble transferrin receptor, haptoglobin, lactate dehydrogenase, and calculated parameters: low hemoglobin density (LHD), red cell size factor (RSF), and microcytic anemia factor (MAF). RESULTS: Discriminant analysis indicated statistically significant differences in the first discriminant function: Function 1 - body iron, LHD, MAF, sTfR, and RSF (P < 0.001) in patients with acyanotic congenital heart disease and significant differences in both discriminant functions in patients with cyanotic congenital heart disease: Function 1 - body iron, soluble transferrin receptor, LHD, RSF, MAF, lactate dehydrogenase, and haptoglobin (P = 0.008) and Function 2 - reticulocytes (#), immature reticulocyte fraction and reticulocytes (%) (P = 0.049). CONCLUSIONS: Beside parameters that describe iron metabolism dynamics (body iron and soluble transferrin receptor), LHD, indicator of hypochromia, have the highest potential to differentiate and classify iron deficiency in patients with congenital heart disease.

Proxidant* antioxidant balance in supplemented elite female volleyball athletes during a six week training period.

AIM: The objectives of this study were: 1) to evaluate pro-oxidant-antioxidant balance (PAB) associations with the commonly measured parameters of oxidative stress and antioxidatve defence in elite female volleyball athletes; 2) to investigate changes in the parameters of oxidative stress during a period of intense training and dietary antioxidant supplementation. METHODS: Twenty-seven female volleyball players participated in this study. Blood samples were collected the day before the pre-competitive mesocycle training period began. After the first blood sample donation and during the next six weeks fourteen players (supplemented group) received a cocktail of antioxidants while thirteen of them (control group) received no dietary supplementation. The following parameters were measured: reactive oxygen metabolites (ROMs), superoxide anion (O2-), malondialdehyde (MDA), advanced oxidation protein products (AOPP), lipid hydroperoxides (LOOH), biological antioxidative potential (BAP), paraoxonase activity toward paraoxon (POase) and diazoxon (DZOase), superoxide dismutase (SOD), total sulphydryl group concentration (SH groups) and pro-oxidant-antioxidant balance. RESULTS: Significant associations were observed between biomarkers of oxidative damage with PAB in multiple linear regression model in the supplemented and the control groups (82.3% vs. 83.1%) before training and in the control group (82.1%) after training. Significant associations between antioxidative defence parameters and PAB values were found in the supplemented group after six-weeks of training (57%). CONCLUSION: In the absence of antioxidant supplementation, PAB values were dependent on the association with biomarkers of oxidative damage before and after training. After a six-week training period and the applied antioxidant supplementation, PAB values were under the influence of non-enzymatic anti-oxidative defence.

Gender-specific oxidative stress parameters.

The aim of the present study was to examine the association of proteins that regulate iron transport/storage content and acute phase response with oxidative stress in male and female athletes. Serum ferritin, transferrin, soluble transferrin receptor, C-reactive protein, interleukin-6 and oxidative stress parameters (reactive oxygen metabolites, superoxide anion, advanced oxidation protein products, lipid hydroperoxides, superoxide-dismutase and pro-oxidant-antioxidant balance) were determined in 138 athletes (73 females and 65 males). A general linear model indicated significant gender differences between athletes in terms of reactive oxygen metabolites (307.48 ± 61.02 VS. 276.98 ± 50.08; P=0.030), superoxide-dismutase (114.60 ± 41.64 VS. 101.42 ± 38.76; P=0.001), lipid hydroperoxides (149.84 ± 38.95 VS. 101.43 ± 39.26; P<0.001), pro-oxidant-antioxidant balance (512.40 ± 148.67 VS. 413.09 ± 120.30; P=0.002), advanced oxidation protein products (1.49 ± 0.30 VS. 0.91 ± 0.25; P<0.001) and superoxide (2.61 ± 0.36 VS. 2.22 ± 0.35; P=0.001), which were all significantly higher in females. Multivariate analysis of covariance indicated gender (P<0.001), training experience (P=0.004), C-reactive protein (P=0.002), soluble transferrin receptor (P=0.004) and transferrin (P<0.001) as significant covariates. Gender accounted for the largest proportion of variability for all oxidative stress parameters (46.3%) and female athletes were more susceptible to oxidative stress. Iron transport and storage proteins (transferrin and ferritin), but also acute phase reactants, were negatively related factors for oxidative stress. In conclusion, variation in the ferritin level may contribute to the different oxidative stress level between the sexes.

Aerobic exercise training as a potential source of natural antibodies protective against human immunodeficiency virus-1.

Despite the effectiveness of HAART in controlling HIV-1 replication, the emergence of drug-resistant viruses in infected patients and the severe side effects caused by the currently used drug regimens and the lack of an effective vaccine necessitate the continued search for new therapeutic strategies for prevention and therapy of HIV disease. Previously we reported that natural autoantibodies, recognizing peptide FTDNAKTI (peptide NTM1) derived from the C2 domain of HIV-1 gp120, contribute to the control of HIV disease. Here we demonstrated that sera from well-trained athletic (HIV-negative) subjects showed high reactivity with peptide NTM1. This result confirms that aerobic exercise training stimulates production of natural autoantibodies, which recognize peptide NTM1. Bioinformatics analysis indicates that these natural autoantibodies could slow down disease progression by blocking the superantigenic site on HIV-1 gp120. The results suggest that aerobic exercise training may be a promising non-toxic and inexpensive adjunctive anti-HIV therapy.

Long-term effects of oxidative stress in volleyball players.

The aim of this study was to determine the impact of long-term training on elite female volleyball players and to determine parameters that could discriminate them according to the level of oxidative stress-associated adaptation. Fifty-four elite female volleyball players were divided into 3 groups (1: below-average training experience <8.0 years, 2: average training experience between 8.0 and 10.5 years and 3: above-average training experience >10.5 years). The measured parameters were reactive oxygen metabolites, biological anti-oxidative potential, superoxide anion, malondialdehyde, advanced oxidation protein products, lipid hydroperoxides, paraoxonase activity, superoxide-dismutase activity and sulphydryl groups. Multiple discriminant analysis of the oxidative stress status parameters between the three groups of athletes indicated a statistically significant difference (Wilks' lambda=0.458, X(2)=35.898, p=0.031). The most important discriminant variables, superoxide-dismutase and superoxide anion, were the best indicators of differences between groups with different training experience. The significantly higher values were found in Group 3 compared with Group 1 in superoxide-dismutase activity (141+/-32 vs. 86+/-46; p=0.002), sulphydryl groups (p=0.031), and reactive oxygen metabolites (p=0.042). The significantly lower superoxide anion was found between Group 3 and Group 1 (377+/-187 vs. 1183+/-905; p=0.001). Oxidative stress status parameters adequately discriminated 68.5% of athletes with different training experience.

Could depression be a new branch of MIA syndrome?

The aims of the present study were to determine the prevalence of depression in our dialysis patients, to detect the most powerful variables associated with depression, and to determine the role of depression in prediction of mortality. The prospective follow-up study of 128 patients (77 HD and 51 CAPD, 65 male, aged 53.8 +/- 13.5 years, dialysis duration 64.7 +/- 64.8 months) was carried out over 36 months. Depression by the Beck Depression Inventory-BDI-II score, laboratory parameters (hemoglobin, serum albumin and creatinine concentration), immunological status (cytokines and hsCRP), comorbidity by Index of Physical Impairment (IPI) and adequacy of dialysis by Kt/V were monitored. The overall prevalence of depression in the dialysis patients (BDI score > or = 14) was 45.3%, and 28.2%, respectively, for moderate and severe depression (BDI > or = 20). The most powerful variable associated with depression was IL-6, but associations with albumin, hemoglobin, creatinine and IPI score were also found. During the follow-up period 36 patients died, 7 patients left the cohort and 2 patients were transplanted. If IPI score was not included in the multivariate Cox analysis, the BDI score remained one of the best predictors of mortality along with albumin. In conclusion, because of the close association of depression with inflammation, malnutrition, and cardiovascular mortality, it could be speculated that depression is one branch of the MIA (malnutrition, inflammation, atherosclerosis) syndrome.

Efficacy of hyperphosphatemia control in the progression of chronic renal failure and the prevalence of cardiovascular calcification.

BACKGROUND AND AIMS: Chronic kidney disease mineral- and bone disorder (CKD-MBD) has been studied more often in dialysis than in predialysis CKD patients. The association between efficacy of hyperphosphatemia control and chronic renal failure (CRF) progression, prevalence of bone disease and cardiovascular calcification was the objective of the present investigation. MATERIAL AND METHODS: 42 patients with CKD in Stage 5, regularly monitored for 5 years, were divided into Group 1 of 20 patients with normal serum phosphate (sPO4) levels and Group 2 of 22 patients with hyperphosphatemia registered at the majority of checks. Serum urea, creatinine, calcium (sCa) and sPO4 levels were regularly determined in the retrospective 5-year period. At the end of this period iPTH, bone alkaline phosphatase-BAP and inflammation markers (CRP, fetuin-A) were measured, valvular and arterial calcifications were detected by B mode echocardiogram and soft-tissue native radiograms of the pelvis and the wrist. RESULTS: Progression of CRF (1/sCr over time) was faster in Group 2 than in Group 1 (b = -0.0577 vs. -0.0288, p = 0.003) during the study period. Average BAP and iPTH values were similar in both groups and 23/42 patients had PTH > 300 pg/ml. Arterial and valvular calcifications were found in 5/23 patients from Group 1 and 14/22 patients from Group 2 (p = 0.011). Linear regression analysis revealed sPO4 as a predictor for total calcification number, inflammatory diseases as a predictor for valvular calcifications, while sPO4 and iPTH were predictors for arterial calcifications. CONCLUSIONS: More than half the patients with Stage 5 CKD not yet on dialysis exhibited elevated PTH. Faster CRF progression and frequent arterial and valvular calcifications were seen in patients with poor phosphate control and sPO4 was selected as an independent predictor of total calcification score.