Oxidative stress markers in pre-uremic patients.

AIM: The present study was designed to investigate a complex of oxidative stress (OS) markers in patients with chronic renal failure (CRF) and to study the relationship between different OS markers and degree of renal failure. The following indices of OS were measured in plasma: oxidized glutathione (GSSG), reduced glutathione (GSH), total glutathione (TGSH), glutathione redox ratio (GSSG/GSH) and resistance of lipoprotein fraction to oxidation (lag phase of LPF). Baseline diene conjugation level of lipoprotein fraction (BDC-LPF), total antioxidative activity (TAA), diene conjugates (DC), lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS) were measured in serum. All markers in plasma and serum were measured both in patients with CRF and in healthy controls. SUBJECTS AND METHODS: Blood samples were obtained from 38 patients with CRF and from 61 healthy controls. Routine biochemical analyses were performed by using commercially available kits. RESULTS: Levels of DC, BDC-LPF, LOOH, GSSG and GSSG/GSH ratio were significantly increased and lag phase of LPF was significantly shortened in patients with CRF compared with healthy controls. Serum creatinine and urea levels correlated significantly with GSSG level and GSSG/GSH in patients with CRF. A significant inverse correlation was found between glutathione redox ratio and lag phase of LPF and between GSSG level and BDC-LPF. CONCLUSIONS: The findings suggest that renal patients are in a state of oxidative stress compared with healthy controls. The most informative indices to evaluate the degree of OS in CRF were: GSSG level, GSSG/GSH status, lag phase of LPF and BDC-LPF.     

Differential effects of nebivolol and metoprolol on central aortic pressure and left ventricular wall thickness

The aim of this study was to investigate the effects of the vasodilating β-blocker nebivolol and the cardioselective β-blocker metoprolol succinate on aortic blood pressure and left ventricular wall thickness. We conducted a randomized, double-blind study on 80 hypertensive patients. The patients received either 5 mg of nebivolol or 50 to 100 mg of metoprolol succinate daily for 1 year. Their heart rate, central and brachial blood pressures, mean arterial pressure, augmentation index, carotid-femoral pulse wave velocity, and left ventricular wall thickness were measured at baseline and at the end of the study. Nebivolol and metoprolol significantly reduced heart rate, brachial blood pressure, and mean arterial pressure to the same degree. However, reductions in central systolic and diastolic blood pressures, central pulse pressure, and left ventricular wall thickness were significant only in the nebivolol group. The change in left ventricular septal wall thickness was significantly correlated with central systolic blood pressure change (r=0.41; P=0.001) and with central pulse pressure change (r=0.32; P=0.01). No significant changes in augmentation index or carotid-femoral pulse wave velocity were detected in either treatment group. This proof-of-principle study provides evidence to suggest that β-blockers with vasodilating properties may offer advantages over conventional β-blockers in antihypertensive therapy; however, this remains to be tested in a larger trial.     

Acute immune response in respect to exercise-induced oxidative stress

The relationship between exhaustive exercise, oxidative stress, the protective capacity of the antioxidant defense system and cellular immune response has been determined. Exhaustive exercise in well-trained young men (n=19)-induced leukocytosis, decreased proportion of activated-lymphocyte subsets (CD4+ and CD8+) expressing CD69, decreased lymphocyte mitogenic response to concanavalin A (ConA) and phytohemagglutinin (PHA), increased lipid peroxidation, increased total antioxidant status (TAS) and catalase activity, immediately after exercise. Suppressed blood concentration of T-lymphocyte subsets (CD3+, CD4+, CD8+, NK), increased TAS and blood total glutathione (TGSH) in early recovery period (30 min after exercise) were found. Strong positive correlation was observed between TGSH and lymphocyte mitogenic response to ConA and PHA (r=0.85 and 0.85, respectively) immediately after exercise. Moderate positive correlation was observed between TAS and lymphocyte mitogenic response to PHA (r=0.59) immediately after exercise as well as between TAS and lymphocyte mitogenic response to PHA and ConA (r=0.69 and 0.54, respectively). Moderate to weak correlation was observed between TAS and conjugated dienes with exercise (r=0.66) as well as in 30-min recovery (r=0.50). After a short-term bout of exhaustive exercise, immune system was characterized by acute phase response, which was accompanied with oxidative stress. Suppression of the cellular immunity 30 min after exercise shows that this period is not enough for recovery after exhaustive exercise. The results suggest the interactions between exercise-induced oxidative stress and immune response.     

Vitamin D Supplementation Has No Impact on Cardiorespiratory Fitness,but Improves Inflammatory Status in Vitamin D Deficient Young Men Engaged in Resistance Training

Data on the effect of vitamin D (Vit-D) supplementation on cardiorespiratory fitness (VO₂max) are conflicting. A possible source of discrepancies in the literature is the heterogeneity in baseline Vit-D status among participants in previous studies. The main objectives of the present study were to assess the impact of Vit-D supplementation on VO₂max and inflammatory status in Vit-D deficient young healthy men. Participants (n = 39, baseline serum Vit-D level < 50 nmol/L) were quasi-randomly assigned to one of the two groups, which, in a double-blind manner, supplemented their diet daily with either Vit-D (8000 IU; VD) or placebo (PLC) and concomitantly performed a 12-week supervised resistance training program. During the 12-week intervention, serum Vit-D concentrations increased 3.9-fold (p < 0.001) in the VD group while no changes occurred in the PLC group. Baseline VO₂max did not differ in the two groups and remained unchanged during the intervention. Serum interleukin-10/tumour necrosis factor alpha ratio increased significantly (30%, p = 0.007; effect size 0.399) in VD but not in PLC group. In conclusion, 12-week Vit-D supplementation increases serum 25(OH)D levels and improves inflammatory status, but has no impact on VO₂max in Vit-D deficient young men engaged in resistance training.     

Prevalence of asthma and bronchial hyperreactivity in Danish schoolchildren: no change over 10 years

Aim: To describe the point prevalence of current physician‐diagnosed asthma and bronchial hyperreactivity (BHR) in 2001 among unselected Danish schoolchildren aged 6–17 years, compared with the prevalence from a similar study from 1990 to 1991. Methods: Cross‐sectional study using parental questionnaire on asthma and respiratory symptoms combined with a 6‐min free running test with peak expiratory flow rate (PEFR) measurement (n = 1051, response rate 89.3%). Results were compared with those of a similar study in the same area from 1990 to 1991. Main outcome measures were current physician‐diagnosed asthma or BHR in children without physician‐diagnosed asthma measured by either a decrease in lung function after standardized running test and/or variability in PEFR on home monitoring. Results: The prevalence of current physician‐diagnosed asthma was 4.0% [95% confidence interval (CI) 2.7–5.3%] in 1990–1991 and 3.6% (95% CI 2.4–4.8%) in 2001. The prevalence of BHR was 3.2% (95% CI 2.0–4.4%) in 1990–1991 and 2.0% (95% CI 1.1–2.9%) in 2001. The combined prevalence was 7.2% (95% CI 5.4–8.9%) in 1990–1991 and 5.6% (95% CI 4.2–7.1%) in 2001. Conclusion: The point prevalence of current physician‐diagnosed asthma and BHR among unselected Danish schoolchildren aged 6–17 years was unchanged over 10 years between 1990–1991 and 2001.     

Preoperative methylprednisolone does not reduce loss of knee-extension strength after total knee arthroplasty

Background and purpose — Patients undergoing total knee arthroplasty (TKA) face challenges related to postoperative reduction in knee-extension strength. We evaluated whether inhibition of the inflammatory response by a single preoperative dose of methylprednisolone (MP) reduces the pronounced loss of knee-extension strength at discharge after fast-track TKA.

Patients and methods — 70 patients undergoing elective unilateral TKA were randomized (1:1) to preoperative intravenous (IV) MP 125?mg (group MP) or isotonic saline IV (group C). All procedures were performed under spinal anesthesia without tourniquet, and with a standardized multimodal analgesic regime. The primary outcome was change in knee-extension strength from baseline to 48?hours postoperatively. Secondary outcomes were knee joint circumference, functional performance using the Timed Up and Go (TUG) test, pain during the aforementioned tests, rescue analgesic requirements, and plasma C-reactive protein (CRP) changes.

Results — 61 patients completed the follow-up. The loss in quadriceps muscle strength was similar between groups; group MP 1.04 (0.22–1.91) Nm/kg (–89%) vs. group C 1.02 (0.22–1.57) Nm/kg (–88%). Also between-group differences were similar for knee circumference, TUG test, and pain scores. MP reduced the inflammatory response (CRP) at 24?hours postoperatively; group MP 33 (IQR 21–50) mg/L vs. group C 72 (IQR 58–92) mg/L (p < 0.001), and 48?hours postoperatively; group MP 83 (IQR 56–125) mg/L vs. group C 192 (IQR 147–265) mg/L (p < 0.001), respectively.

Interpretation — Preoperative systemic administration of MP 125?mg did not reduce the pronounced loss of knee-extension strength or other functional outcomes at discharge after fast-track TKA despite a reduced systemic inflammatory response.     

17beta-Oestradiol stimulation of G-proteins in aged and Alzheimer's human brain: comparison with phytoestrogens

The neuroprotective action of oestrogens and oestrogen-like compounds is in the focus of basic and clinical research. Although such action has been shown to be associated with neuronal plasma membranes, the implication of G-proteins remains to be elucidated. This study revealed that micromolar concentrations (microM) of 17beta-oestradiol and phytoestrogens, genistein and daidzein, significantly (P < 0.05) stimulate G-proteins ([(35)S]GTP gamma S binding) in the post-mortem hippocampal membranes of age-matched control women with the respective maximum effects of 28, 20 and 15% at 10 microM. In the frontocortical membranes, the stimulation of G-proteins did not differ significantly from that in hippocampal membranes. Although in the hippocampus and frontal cortex of the Alzheimer's disease (AD) women's brain, 10 microM 17beta-oestradiol produced significantly (P < 0.05) lower stimulation of G-proteins than in the control regions, stimulation by phytoestrogens revealed no remarkable decline. 17beta-Oestradiol, genistein and daidzein revealed a selective effect on various G-proteins (G(alphas), G(alpha o), G(alpha i1) or G(alpha 11) plus G(beta 1 gamma 2)) expressed in Sf9 cells. At a concentration of 10 microM, 17beta-oestradiol suppressed the H(2)O(2) and homocysteine stimulated G-proteins in the frontocortical membranes of control women to a greater extent than phytoestrogens. In AD, the suppressing effect of each compound was lower than in the controls. In the cell-free systems, micromolar concentrations of phytoestrogens scavenged OH(*) and the 2.2-diphenyl-1-picrylhydrazyl free radical (DPPH(*)) more than 17beta-oestradiol did. In the frontocortical membranes of control women, the 20 microM 17beta-oestradiol stimulated adenylate cyclase with 20% maximal effect, whereas, in AD, the effect was insignificant. Genistein did not stimulate enzyme either in control or AD frontocortical membranes. Our data confirm that the agents stimulate G-proteins in control and AD women's brains, although 17beta-oestradiol and phytoestrogens have similarities and differences in this respect. We suggest that, besides the ER-dependent one, the ER-independent antioxidant mechanism is responsible for the oestrogen stimulation of G-proteins in the brain membranes. Both of these mechanisms could be involved in the neuroprotective signalling of oestrogens that contributes to their preventive/therapeutic action against postmenopausal neurological disorders.     

Effects of 60 minutes of hyperoxia followed by normoxia before coronary artery bypass grafting on the inflammatory response profile and myocardial injury

Background

Ischemic preconditioning induces tolerance against ischemia-reperfusion injury prior a sustained ischemic insult. In experimental studies, exposure to hyperoxia for a limited time before ischemia induces a low-grade systemic oxidative stress and evokes an (ischemic) preconditioning-like effect of the myocardium. We hypothesised that pre-treatment by hyperoxia favours enchanced myocardial protection described by decreased release of cTn T in the 1^st postoperative morning and reduces the release of inflammatory cytokines.

Methods

Forty patients with stable coronary artery disease underwent coronary artery bypass grafting with cardiopulmonary bypass. They were ventilated with 40 or >96% oxygen for 60 minutes followed by by 33 (18?C59) min normoxia before cardioplegia.

Results

In the 1^st postoperative morning concentrations of cTnT did not differ between groups ((0.44 (0.26-0.55) ng/mL in control and 0.45 (0.37-0.71) ng/mL in hyperoxia group). Sixty minutes after declamping the aorta, ratios of IL-10/IL-6 (0.73 in controls and 1.47 in hyperoxia, p?=?0.03) and IL-10/TNF-?? (2.91 and 8.81, resp., p?=?0.015) were significantly drifted towards anti-inflammatory, whereas interleukins 6, 8and TNF-?? and interferon-?? showed marked postoperative rise, but no intergroup differences were found.

Conclusions

Pre-treatment by 60 minutes of hyperoxia did not reduce postoperative leak of cTn T in patients undergoing coronary artery bypass surgery. In the hyperoxia group higher release of anti-inflammatory IL-10 caused drifting of IL-10/IL-6 and IL-10/TNF-?? towards anti-inflammatory.     

Lower bone mineral density in children with type 1 diabetes is associated with poor glycemic control and higher serum ICAM-1 and urinary isoprostane levels

The purpose of the study was to investigate bone mineral density (BMD) in children with type 1 diabetes (DM1) and to establish the relationships between BMD, physical activity, glycemic control, and markers of systemic oxidative stress and inflammation. We studied 30 children with DM1, aged 4.7–18.6 years, and 30 healthy subjects, matched by sex, age, and body mass index (BMI). Mean duration of DM1 was 5.4 ± 3.4 years and mean glycosylated hemoglobin (HbA_1c) level over 12 months was 9.8 ± 1.5%. Lumbar and total bone mineral density (BMD, g/cm²) were measured by dual-energy X-ray absorptiometry (DXA). We calculated the apparent volumetric lumbar BMD (BMDvol, g/cm³) and total mineral content adjusted for age and height (BMCadj), and measured plasma intercellular adhesion molecule-1 (ICAM-1), high sensitivity C-reactive protein (hs-CRP), and urinary 8-iso-prostaglandin F_2a (F₂-IsoPs). Calcium (Ca) intake was assessed by questionnaire and physical activity by questionnaire and accelerometer (ActiGraph, count/h). Total BMCadj and lumbar BMDvol were significantly lower in children with DM1 than in controls (101.8 ± 7.7 vs. 107 ± 5.7%, P = 0.005; 0.32 ± 0.08 vs. 0.36 ± 0.09 g/cm³, P = 0.05, respectively). These differences were mostly caused by the differences in boys. Plasma ICAM-1 and hs-CRP levels were significantly higher in the DM1 group compared to the controls. Ca intake and urine F₂-IsoPs levels were similar between the groups. Diabetic boys were less active than controls (18231 ± 6613 vs. 24145 ± 7449 count/h, P = 0.04). In the DM1 group, lumbar BMDvol correlated inversely with urinary F₂-IsoPs (r = −0.5; P = 0.005) and plasma ICAM-1 levels (r = −0.4; P = 0.02), and also with HbA_1c levels after adjustment for age (r = −0.45; P < 0.05). Total BMCadj correlated inversely with HbA_1c levels (r = −0.4; P = 0.02). We conclude that children with DM1, particularly boys, have lower BMD. Poor glycemic control, elevated markers of oxidative stress, and inflammation are associated with lower BMD.