Inverse relations of serum phosphatidylcholines and lysophosphatidylcholines with vascular damage and heart rate in patients with atherosclerosis.

BACKGROUND AND AIMS: The rapidly growing discipline of lipidomics allows the study of a wide spectrum of lipid species in body fluids and provides new insights into the pathogenesis of cardiovascular disease. We investigated serum phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) species in relation to arterial stiffness, hemodynamics, and endothelial dysfunction in symptomatic patients with atherosclerosis and in healthy controls. METHODS AND RESULTS: Thirty-two patients with peripheral arterial disease (age 61.7 ± 9.0 years), 52 patients with coronary artery disease (age 63.2 ± 9.2 years), and 40 apparently healthy controls (age 60.3 ± 7.1 years) were studied. Serum levels of 90 glycerophospholipids were determined with the AbsoluteIDQ™ p180 kit (BIOCRATES Life Sciences AG, Innsbruck, Austria). The technique of applanation tonometry was used for non-invasive pulse wave analysis and carotid-femoral pulse wave velocity (cf-PWV) assessment. Decreased serum levels of several individual PC and lysoPC species (e.g., PC aa C28:1, PC aa C30:0, PC aa C32:2, PC ae C30:0 and PC ae C34:2, lysoPC a C18:2) were observed for the patient groups in comparison to the healthy subjects. In addition, a considerable number of PCs and lysoPCs were inversely related to either cf-PWV, heart rate, asymmetric dimethylarginine (ADMA) or ADMA/arginine for patients with symptomatic atherosclerosis but not for the controls. CONCLUSION: We found altered relationships between PC and lysoPC profiles, inflammation, and arterial function in atherosclerotic patients, compared to healthy subjects.

Association Between Fibulin-1 and Aortic Augmentation Index in Male Patients with Peripheral Arterial Disease.

BACKGROUND: Fibulin-1 (FBLN-1), a newly identified biomarker for vascular stiffness in type 2 diabetes, may participate in the pathophysiological processes leading to progression of arterial stiffness in atherosclerosis. In the present study, the relationship between FBLN-1 and arterial stiffness was examined in patients with atherosclerosis and in healthy subjects. METHODS: Thirty-eight patients with peripheral arterial disease (PAD) (age 62.4 ± 9.0 years), 38 patients with coronary artery disease (CAD) (age 64.0 ± 9.5 years), and 30 apparently healthy controls (age 61.1 ± 6.4 years) were studied. Serum FBLN-1, oxidized low density lipoprotein (oxLDL), resistin and plasminogen activator inhibitor-1 (PAI-1) levels were measured using the enzyme linked immunosorbent assay method. The technique of applanation tonometry was used for non-invasive pulse wave analysis and pulse wave velocity assessments. RESULTS: The levels of FBLN-1 (PAD = 9.4 [4.9-17.8] vs. CAD = 7.1 [4.8-11.8] vs. controls = 5.6 [4.1-8.4] µg/mL; p = .005), carotid-femoral pulse wave velocity (cf-PWV) (9.8 ± 2.2 vs. 9.5 ± 2.2 vs. 8.3 ± 2.2 m/s; p = .023) and the heart rate corrected augmentation index (AIx@75) (29.4 ± 7.2 vs. 19.2 ± 7.2 vs. 15.4 ± 7.1%; p < .001), differed among the three groups. A correlation between FBLN-1 and AIx@75 was observed only in patients with PAD (rho = 0.37, p = .021). The relationship retained statistical significance in a multiple regression model after adjustment for potential confounders. CONCLUSIONS: An independent association was demonstrated between serum FBLN-1 and AIx@75 in the PAD group. Thus, the findings suggest that FBLN-1 may play a role in arterial stiffening in patients with atherosclerosis.

Wfs1-deficient animals have brain-region-specific changes of Na+, K+-ATPase activity and mRNA expression of α1 and ß1 subunits.

Mutations in the WFS1 gene, which encodes the endoplasmic reticulum (ER) glycoprotein, cause Wolfram syndrome, a disease characterized by juvenile-onset diabetes mellitus, optic atrophy, deafness, and different psychiatric abnormalities. Loss of neuronal cells and pancreatic ß-cells in Wolfram syndrome patients is probably related to the dysfunction of ER stress regulation, which leads to cell apoptosis. The present study shows that Wfs1-deficient mice have brain-region-specific changes in Na(+),K(+)-ATPase activity and in the expression of the α1 and ß1 subunits. We found a significant (1.6-fold) increase of Na-pump activity and ß1 subunit mRNA expression in mice lacking the Wfs1 gene in the temporal lobe compared with their wild-type littermates. By contrast, exposure of mice to the elevated plus maze (EPM) model of anxiety decreased Na-pump activity 1.3-fold in the midbrain and dorsal striatum and 2.0-fold in the ventral striatum of homozygous animals compared with the nonexposed group. Na-pump α1 -subunit mRNA was significantly decreased in the dorsal striatum and midbrain of Wfs1-deficient homozygous animals compared with wild-type littermates. In the temporal lobe, an increase in the activity of the Na-pump is probably related to increased anxiety established in Wfs1-deficient mice, whereas the blunted dopamine function in the forebrain of Wfs1-deficient mice may be associated with a decrease of Na-pump activity in the dorsal and ventral striatum and in the midbrain after exposure to the EPM.

Prognostic impact of arterial stiffness in patients with symptomatic peripheral arterial disease.

OBJECTIVES: Arterial stiffness (AS) is increasingly recognized as an independent risk factor in different high-risk populations. Whether changes in AS can predict prognosis in patients with symptomatic peripheral arterial disease (PAD) has never been investigated. The aim of the present study was to test the hypothesis that AS is an independent predictor of all-cause and cardiovascular disease (CVD) mortality in patients with symptomatic PAD. METHODS: A cohort of 117 symptomatic PAD patients (aged 62.3 ± 7.7 years) were prospectively recruited from the Department of Vascular Surgery, Tartu University Hospital, between 2002 and 2010. The AS was measured using pulse wave analysis and assessment of pulse wave velocity (PWV). RESULTS: During the follow-up period (mean 4.1 ± 2.2 years) there were 32 fatal events. Kaplan-Meier analysis showed that the probability of all-cause and CVD mortality decreased with increasing small artery elasticity (SAE), as estimated by the log-rank test (p = .004; p = .005, respectively). By contrast, large artery elasticity, augmentation index, and aortic and brachial PWV were not significantly related to mortality. In a Cox proportional hazard model, SAE above the median was associated with decreased all-cause and CVD mortality after adjustment for confounding factors: relative risk (RR), 0.37; 95% confidence interval (CI), 0.17-0.81; p = .01; RR, 0.11; 95% CI, 0.01-0.86; p = .04, respectively). CONCLUSIONS: This study provides the first evidence, obtained from an observational study, that decreased small artery elasticity is an independent predictor of all-cause and CVD mortality in patients with symptomatic PAD.

Serum interferon gamma concentration is associated with bone mineral density in overweight boys.

UNLABELLED: Childhood obesity has recently been linked to low-grade inflammation. Overweight children have slightly different processes of bone accumulation than normal weight children. The possible links between inflammation and bone accumulation have not previously been assessed in overweight children. AIMS: An exploratory study to assess whether common inflammatory markers are associated with the development of obesity and bone accumulation in childhood. METHODS: Thirteen different inflammatory markers in serum were measured in 38 boys with BMI >85th centile (overweight) and 38 boys with normal BMI (normal weight), aged 10-11 years. Total body (TB) and lumbar spine (LS) bone mineral density (BMD), bone mineral content (BMC) were measured by DXA. TB BMC for height, TB and LS bone mineral apparent density (BMAD) were calculated. RESULTS: Overweight boys had higher mean TB and LS BMD, TB BMC and TB BMC for height, but lower mean TB BMAD (all p < 0.05) than normal weight boys. Serum interferon gamma (IFNγ) concentration was significantly (p < 0.05) correlated with TB BMD (r = 0.36), TB BMC (r = 0.38) and TB BMC for height (r = 0.53) in the broader overweight group (n = 38). In obese boys (BMI > 95 centile, n = 36) IFNγ was correlated with LS BMD (r = 0.38). CONCLUSION: The positive correlation between serum INFγ concentration and BMD suggests that the inflammatory process, already involved in the early stage of obesity, may also affect bone accumulation. Further studies are needed to clarify the role of INFγ as a possible link between adipose tissue and bone health.

Comparative study of systemic inflammatory responses in psoriasis vulgaris and mild to moderate allergic contact dermatitis.

BACKGROUND: Psoriasis vulgaris (PV) is associated with low-grade systemic inflammation. OBJECTIVE: Cytokines' and growth factors' serum patterns in patients with PV, allergic contact dermatitis (ACD) and healthy subjects were investigated to describe and compare systemic inflammatory responses in these diseases. METHODS: A total of 12 inflammation-sensitive biomarkers were analyzed simultaneously by means of the Evidence Investigator™ biochip technology. RESULTS: In PV, proinflammatory tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukins (IL)-1ß, -2, -6, -8, and monocyte chemoattractant protein (MCP)-1 were elevated. In ACD, 2 markers, TNF-α and MCP-1, were increased, and regulatory cytokine IL-10 was decreased. Proinflammatory IL-2 had the strongest correlations with other pro- as well as anti-inflammatory cytokines in PV and ACD, whilst IL-6 correlated positively with the Psoriasis Area and Severity Index. Growth factors' levels correlated with MCP-1, but only in PV. CONCLUSION: Although psoriasis induces a more variegated proinflammatory systemic response, ACD is likewise associated with a systemic increase in inflammatory mediators.

[Effect of probiotic Heart cheese "Harmony" comprising bacteria L. plantarum TENSIA DSM 21380 on blood pressure and metabolic health indices].

The probiotic L. plantarum strain TENSIA (DSM 21380) is a novel microorganism having antimicrobial and antihypertensive properties. The aim of the study was to test the efficacy of the consumption of the cheese, comprising the novel strain TENSIA on multiple health markers of humans. Human intervention trial showed that the blood pressure lowering effect of cheese, comprising L. plantarum TENSIA was evident in healthy volunteers with high normal blood pressure up to normal values. The 3-week consumption of the prohiotic cheese did not increase the CVD risk factors like BMI, the level of plasma lipids and glucose as well as inflammatory and immunological markers of human body.

Aortic stiffness and vitamin D are independent markers of aortic calcification in patients with peripheral arterial disease and in healthy subjects.

OBJECTIVE: Arterial stiffness is a significant determinant of cardiovascular risk and is related to vascular calcification. Vitamin D may regulate arterial calcification and has been associated with cardiovascular survival benefits. However, data about the relationship between arterial stiffness, aortic calcification and vitamin D levels in patients with peripheral arterial disease (PAD) and in healthy subjects are limited. We examined the potential association between aortic calcification, arterial stiffness and vitamin D levels in patients with symptomatic PAD and in healthy individuals. METHODS: We studied 78 men with PAD (aged 63 ± 7 years) and 74 healthy men (aged 61 ± 10 years). Aortic pulse wave velocity (aPWV) was determined by applanation tonometry using the Sphygmocor device. Aortic calcification score (ACS) was quantified by computed tomography. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured using a radioimmune assay. RESULTS: ACS (4.9(2.3-8.9) vs. 0.2(0.03-1.6) (cm³); p < 0.01), aPWV (9.8 ± 2.4 vs. 8.2 ± 1.6 (m s⁻¹; p < 0.01) and 25(OH)D (15.1 ± 5.4 vs. 19.0 ± 5.9 (ng ml⁻¹); p < 0.01) were different in the patients compared with the controls. In multivariate analysis, ACS was independently determined by 25(OH)D, aPWV, calcium and age in patients with PAD (R² = 0.49; p < 0.001) and by 25(OH)D, aPWV, cholesterol/high-density lipoprotein (HDL) and age in the control group (R² = 0.55; p < 0.001). Increased aPWV and lower levels of 25(OH)D were associated with decreased ankle-brachial pressure index (p = 0.03). CONCLUSION: These results indicate that calcification of the aorta is independently associated with aortic stiffness and serum 25(OH)D level in patients with PAD and in healthy subjects. Aortic stiffness and abnormal vitamin D level may contribute to vascular calcification and are related to higher severity grade of atherosclerotic disease.

The levels of adiponectin and leptin and their relation to other markers of cardiovascular risk in patients with psoriasis.

BACKGROUND: A link between psoriasis and risk for cardiovascular disease (CVD) is supposed. Adipokines (adiponectin and leptin) playing roles in inflammation as well as lipid metabolism could have impact on CVD. OBJECTIVES: We investigated links between adiponectin and leptin levels and several inflammation- and oxidative stress-related CVD risk makers in patients with psoriasis. METHODS: Sixty patients with plaque-type psoriasis with normal total cholesterol levels belonging to three body mass index (BMI) categories: BMI < 24.9, BMI 25.0-29.9 and BMI ≥ 30.0 kg/m(2) were studied. Fasting blood samples were analysed for adiponectin, leptin, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), oxidized low density lipoprotein (oxLDL), oxidized LDL/ß(2) -glycoprotein complexes (oxLDL-ß(2)-GPI) and standard blood lipid panel. RESULTS: In patients, adiponectin was negatively (P < 0.005), and leptin, oxLDL and oxLDL-ß(2) -GPI levels were positively correlated to BMI (P < 0.005, P < 0.05, and P < 0.01, respectively). Patients had higher hsCRP and IL-6 levels as compared with the endemic reference values. High adiponectin was strongly associated with higher TNF-α and high density lipoprotein cholesterol (P = 0.001), and lower triglycerides (TG) (P = 0.01) as well as oxLDL-ß(2) -GPI levels (P < 0.05). After multivariate adjustment, the association for TNF-α and TG remained significant (P < 0.01 for both). Multiple regression analysis also revealed that leptin concentration was significantly associated with hsCRP, oxLDL and TG levels. CONCLUSION: The data suggest that in addition to the strong effect of inflammation and LDL oxidation, adipokine level may be one of the mechanisms behind the close association between psoriasis and CVD. Given the significant relations of several markers with BMI, health consequences of excessive weight should be better communicated to patients with psoriasis.

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.

Temperature dependence of the sodium pump is altered in the cerebral cortex of CCK2 receptor-deficient mice.

Previously we have shown that the temperature dependence of the sodium pump (Na(+),K(+)-ATPase) is altered under different neuropathological conditions. In this study we compared temperature dependence of the Na(+),K(+)-ATPase in the fronto-parietal cortex of CCK(2) receptor-deficient (homo- and heterozygous) and normal (wild-type) mice. The Arrhenius plot for Na(+),K(+)-ATPase from wild-type brain is non-linear with a breakpoint at 20.3 +/- 0.4 degrees C. In case of the brain cell membrane of CCK(2) receptor-deficient mice (homo- and heterozygous) the breakpoint on Arrhenius plot was detected at 26.0 +/- 1.1 degrees C and 25.4 +/- 0.4 degrees C, respectively. The shift of the breakpoint on the Arrhenius plot established in CCK(2) receptor-deficiency as well as in case of some other pathological conditions confirms that such kind of alteration in the Na(+),K(+)-ATPase temperature dependence is likely related to the homeostatic adjustment of altered function of the sodium pump.

Complete glutathione system in probiotic Lactobacillus fermentum ME-3.

There is much information about glutathione (GSH) in eukaryotic cells, but relatively little is known about GSH in prokaryotes. Without GSH and glutathione redox cycle lactic acid bacteria (LAB) cannot protect themselves against reactive oxygen species. Previously we have shown the presence of GSH in Lactobacillus fermentum ME-3 (DSM14241). Results of this study show that probiotic L. fermentum ME-3 contains both glutathione peroxidase and glutathione reductase. We also present that L. fermentum ME-3 can transport GSH from environment and synthesize GSH. This means that it is characterized by a complete glutathione system: synthesis, uptake and redox turnover ability that makes L. fermentum ME-3 a perfect protector against oxidative stress. To our best knowledge studies on existence of the complete glutathione system in probiotic LAB strains are still absent and glutathione synthesis in them has not been demonstrated.

Effects of a synbiotic product on blood antioxidative activity in subjects colonized with Helicobacter pylori.

AIM: To evaluate the impact of the consumption of a synbiotic product on the antioxidative activity markers of blood in asymptomatic H. pylori-colonized persons. METHODS AND RESULTS: Fifty-three healthy adult volunteers without gastric symptoms participated in a randomized, double-blind placebo-controlled study. The crossover consumption of the enterocoated capsules containing antioxidative Lactobacillusfermentum ME-3, Lact. paracasei 8700:2 and Bifidobacterium longum 46 with Raftilose P95 lasted for 3 weeks and did not change the H. pylori colonization. In H. pylori-positive subjects the sera values of total antioxidative status (TAS) were significantly lower compared to H. pylori-negative subjects (0.97 vs 1.05 mmol l(-1), P = 0.008). After the consumption of the synbiotic, TAS values (0.97 vs 1.03 mmol l(-1), P = 0.004) increased, while the ratio between oxidized and reduced glutathione (0.035 vs 0.030, P = 0.016) decreased in H. pylori-positive subjects. CONCLUSIONS: The consumption of a synbiotic containing an antioxidative probiotic strain improved the reduced systemic antioxidative activity in H. pylori-colonized asymptomatic subjects. SIGNIFICANCE AND IMPACT OF THE STUDY: A synbiotic product containing an antioxidative probiotic strain may be useful in the reduction of systemic oxidative stress in H. pylori infection.

Clear differences in adiponectin level and glutathione redox status revealed in obese and normal-weight patients with psoriasis.

BACKGROUND: Several studies have shown increased prevalence of obesity in patients with psoriasis. OBJECTIVES: To characterize both inflammatory- and oxidative stress-related differences between obese patients with psoriasis (OPP) and normal-weight patients with psoriasis (NWPP). METHODS: The plasma concentrations of adiponectin and interleukin (IL)-6 were analysed by quantitative sandwich enzyme immunoassay technique in 10 patients with a body mass index (BMI)<25 and 12 patients with a BMI>30. Total glutathione and oxidized glutathione levels were measured spectrophotometrically. RESULTS: Plasma concentration of adiponectin in NWPP was more than twice the level in healthy normal-weight controls (P<0.001), while such an elevation did not occur in OPP. OPP were characterized by a significantly increased IL-6 level, which correlated negatively with the adiponectin level (r=-0.85, P<0.001). The glutathione redox status, which was also inversely correlated with the adiponectin level (r=-0.63, P<0.05), was associated with significantly increased oxidative stress in the OPP compared with the NWPP or controls. CONCLUSIONS: Obesity in patients with psoriasis is associated with both decreased plasma levels of protective adiponectin compared with NWPP, and enhanced systemic inflammation and oxidative stress. These findings are in concordance with high prevalence of diseases related to lower adiponectin levels among psoriasis patients.

Oxidative stress in leucocytospermic prostatitis patients: preliminary results.

The aim of this study was to contribute to the knowledge concerning pathogenesis of inflammatory chronic prostatitis by revealing possible shifts in the balance of markers of oxidative stress and anti-oxidative activity in case of leucocytospermic prostatitis. We also attempted to identify possible relations between seminal micro-organisms and oxidative stress parameters. A many-sided complex of local (spermatozoa, seminal plasma) and general (blood, urine) markers in 21 prostatitis patients and nine controls was compared. In both spermatozoa and seminal plasma, the content of diene conjugates was significantly higher in prostatitis patients compared with healthy controls. At the same time total anti-oxidative status in spermatozoa and total anti-oxidative activity in seminal plasma were lower in prostatitis patients than in controls. In urine, the level of 8-isoprostanes was significantly higher in prostatitis patients than in healthy controls, correlating well with 8-hydroxy-2'-deoxyguanosine. The latter correlated with cellular Fe and Ni contents as well, confirming that these metals with varying valency may cause DNA damage. Reduced glutathione showed higher levels in blood of controls than in prostatitis patients. Coryneform bacteria appeared to be associated with prostatitis-related oxidative stress. In conclusion, leucocytospermic prostatitis patients are characterised by oxidative stress at all levels: systemic (general), seminal plasma and cellular.

Inflammatory, cardio-metabolic and diabetic profiling of chronic schizophrenia.

BACKGROUND: There is a growing interest in low-grade inflammatory and metabolic alterations in patients with chronic schizophrenia (SCH). METHODS: Inflammatory (tumor-necrosis factor-α [TNF-α], interferon-γ [IFN-γ], interleukins [IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10], monocyte chemo-attractant protein-1 [MCP-1]) and growth factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF]) were measured in blood serum samples of 105 SCH patients and 148 control subjects (CS). Simultaneously the clinical biomarkers (C-reactive protein [CRP], triglycerides [TG], low-density lipoprotein [LDL-c] and high-density lipoprotein [HDL-c] cholesterol, glycated hemoglobin [HbA1c]) were measured, and body mass index (BMI) was calculated for patients. RESULTS: Several cyto-/chemokines (IFN-γ, MCP-1, IL-2, IL-6, IL-8 and IL-10) were significantly (P<0.0000001) elevated in SCH patients compared to CS. Odds ratios, obtained from logistic regression analyses, were significantly elevated for IL-2, IL-6, IL-10, INF-γ, and decreased for TNF-α in SCH group. Among the patients, higher IL-2, IL-6, INF-γ and lower MCP-1 levels as well as male gender were together significant (P<0.000001) predictors of higher HbA1c levels, and TG/HDL-c parameter was associated with ratios of INF-γ/IL-10 (P=0.004), and INF-γ/IL-4 (P=0.049), HbA1c (P=0.005), INF-γ (P=0.009), as well as LDL-c (P=0.02) levels. CONCLUSIONS: IL-2, IL-6, IL-10 and IFN-γ were the most significant SCH-related markers among the measured cytokines in our patient group. Furthermore, significant associations between pro-/anti-inflammatory imbalance and HbA1c as well as cardio-metabolic risk marker (TG/HDL-c) were observed, indicating higher risks of diabetes and cardiovascular diseases among SCH patients.

Patients with allergic and irritant contact dermatitis are characterized by striking change of iron and oxidized glutathione status in nonlesional area of the skin.

To assess the consequences of oxidative stress in allergic and irritant contact dermatitis, we compared the iron level, unsaturated iron-binding capacity, total iron binding capacity, the percentage saturation of iron-binding capacity, the amount of diene conjugates as well as the amounts of total glutathione, reduced glutathione, oxidized glutathione, and the oxidized glutathione/reduced glutathione ratio in skin homogenate from lesional and nonlesional skin. Lesional skin samples were obtained from positive patch test sites to 5% NiSO4 in five subjects, and from chronic contact dermatitis lesions on the hands, which had exacerbated over 3--9 wk in six subjects. Contact dermatitis caused at least a 4-fold increase in the iron level in the lesional skin area compared with the nonlesional skin area (p < 0.02). The increase in the iron level depended on the duration of contact dermatitis and was accompanied by high unsaturated iron-binding capacity and total iron-binding capacity values in the positive patch test sites (p < 0.05), and by a high percentage saturation value in the chronic contact dermatitis lesions (p < 0.05). We found high indices for iron, total iron-binding capacity and diene conjugates in the apparently healthy skin of the patients with persistent contact dermatitis that significantly (p < 0.05) exceeded the corresponding values in the patients with only patch test reactions. In summary, we have succeeded in providing evidence that generalized oxidative damage of the skin occurs as a consequence of contact dermatitis in a restricted area.

Activation of Na,K-ATPase by an endogenous peptide, PEC-60.

Several peptidic and non-peptidic factors can modulate Na,K-ATPase activity, among them mainly inhibitors of this enzyme, ouabain being the most effective. In a very few cases only, activation of Na,K-ATPase by endogenous factors has been recorded. We have investigated the effect on Na,K-ATPase of a novel regulatory peptide, PEC-60, recently isolated from porcine intestine. Various biological effects have been described for PEC-60 in different tissues, including brain. We have found that PEC-60 caused a dose-dependent activation of Na,K-ATPase from rat brain frontal cortex, whereas the carboxymethylated form of PEC-60 or other hormonal peptides had no effect. The maximal value of activity reaches up to 125% at close to micromolar concentrations of PEC-60 and the dependence can be described with a bell-shaped curve, indicating a complex mechanism for the interaction. The activation of the enzyme by PEC-60 is apparently related to Na(+)-dependent steps of the Na,K-ATPase system. The kinetic parameters for K(+)-phosphatase were unaffected. Moreover, the activating effect was enhanced by preincubation at low concentrations of ATP that transform the enzyme into the Na(+)-form. Due to the crucial physiological role of Na,K-ATPase, its activity has to be finely controlled and thus PEC-60 may be one of the endogenous factors that regulate this enzyme.

Physical exercise induces activation of NF-kappaB in human peripheral blood lymphocytes.

Current understanding of nuclear factor-kappaB (NF-kappaB) activation is derived mostly from in vitro studies, and in vivo human data are limited. This study provides first evidence showing that physical exercise (80% maximal O2 consumption, 1 h) may trigger NF-kappaB activation, as determined by electrophoretic mobility shift assay, in peripheral blood lymphocytes of physically fit young men. Supershift assay showed that the NF-kappaB protein complex contained the transcriptionally active p65 protein. Plasma levels of NF-kappaB-directed gene products such as tumor necrosis factor-alpha and interleukin-2 receptor confirmed that physical exercise caused NF-kappaB transactivation. Exercise-induced NF-kappaB activation in lymphocytes was associated with elevated levels of lipid peroxidation by-products in the plasma.

High-sensitive C-reactive protein level and oxidative stress-related status in former athletes in relation to traditional cardiovascular risk factors.

OBJECTIVE: To analyze systemic and cellular oxidative stress-related indices as well as C-reactive protein level in former top-level athletes in relation to traditional cardiovascular risk factors. METHODS: A cross-sectional study was performed in 53 former male athletes and 25 sedentary controls (age range: 39-59 years). We measured anthropometric factors (BMI, fat percentage, WHR), resting blood pressure (SBP, DBP), serum cholesterol (CHOL), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), total antioxidant status (TAS), oxidized LDL-C (oxLDL), diene conjugates (DC), glutathione redox status, high-sensitive C-reactive protein (hsCRP), and leisure-time physical activity. RESULTS: Physically active former athletes had significantly lower mean overweight (BMI, fat percentage, WHR), better spectrum of atherogenesis indicators (CHOL, HDL-C, TG, TG:HDL-C ratio) and lower oxidative stress (oxLDL, oxLDL:LDL-C ratio, DC) values than sedentary ex-athletes. No significant differences in these variables were found between the sedentary ex-athletes and control group. Significant associations were found between physical activity (METs), SBP, DBP, hypertension, CHOL, HDL-C, TG, TG:HDL-C ratio, oxLDL, oxLDL:LDL-C ratio, DC and hsCRP. CONCLUSIONS: A physically active lifestyle is related to a lower cardiovascular disease (CVD) risk profile including a substantially lower systemic and cellular oxidative stress status as well as C-reactive protein level in middle-aged men.