Activation of nuclear factor-kappa B subunits c-Rel, p65 and p50 by plasma lipids and fatty acids across the menstrual cycle.

This study focused on a comprehensive analysis of the canonical activation pathway of the redox-sensitive transcription factor nuclear factor-kappa B (NF-κB) in peripheral blood mononuclear cells, addressing c-Rel, p65 and p50 activation in 28 women at early (T1) and late follicular (T2) and mid (T3) and late luteal (T4) phase of the menstrual cycle, and possible relations with fasting plasma lipids and fatty acids. For the first time, strong inverse relations of c-Rel with apolipoprotein B were observed across the cycle, while those with LDL cholesterol, triglycerides as well as saturated (SFA), particularly C14-C22 SFA, monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) clustered at T2. In contrast, p65 was positively related to LDL cholesterol and total n-6 PUFA, while p50 did not show any relations.

From carotenoid intake to carotenoid blood and tissue concentrations - implications for dietary intake recommendations.

There is uncertainty regarding carotenoid intake recommendations, because positive and negative health effects have been found or are correlated with carotenoid intake and tissue levels (including blood, adipose tissue, and the macula), depending on the type of study (epidemiological vs intervention), the dose (physiological vs supraphysiological) and the matrix (foods vs supplements, isolated or used in combination). All these factors, combined with interindividual response variations (eg, depending on age, sex, disease state, genetic makeup), make the relationship between carotenoid intake and their blood/tissue concentrations often unclear and highly variable. Although blood total carotenoid concentrations <1000 nmol/L have been related to increased chronic disease risk, no dietary reference intakes (DRIs) exist.

Identification of blood cell transcriptome-based biomarkers in adulthood predictive of increased risk to develop metabolic disorders using early life intervention rat models.

Calorie restriction during gestation in rats has long-lasting adverse effects in the offspring. It induces metabolic syndrome-related alterations, which are partially reversed by leptin supplementation during lactation. We employed these conditions to identify transcript-based nutrient sensitive biomarkers in peripheral blood mononuclear cells (PBMCs) predictive of later adverse metabolic health.

Urinary Metabolomic Markers of Protein Glycation, Oxidation, and Nitration in Early-Stage Decline in Metabolic, Vascular, and Renal Health.

Glycation, oxidation, nitration, and crosslinking of proteins are implicated in the pathogenic mechanisms of type 2 diabetes, cardiovascular disease, and chronic kidney disease. Related modified amino acids formed by proteolysis are excreted in urine. We quantified urinary levels of these metabolites and branched-chain amino acids (BCAAs) in healthy subjects and assessed changes in early-stage decline in metabolic, vascular, and renal health and explored their diagnostic utility for a noninvasive health screen.

Progesterone-associated arginine decline at luteal phase of menstrual cycle and associations with related amino acids and nuclear factor kB activation.

Background/objectives: Given their role in female reproduction, the effects of progesterone on arginine and related amino acids, polyamines and NF-κB p65 activation were studied across the menstrual cycle.

Methods: Arginine, ornithine and citrulline as well as putrescine, spermidine, spermine, and N-acetyl-putrescine were determined in plasma, NF-κB p65 activation in peripheral blood mononuclear cells and progesterone in serum of 28 women at early (T1) and late follicular (T2) and mid (T3) and late (T4) luteal phase.

Results: Arginine and related amino acids declined from T1 and T2 to T3 and T4, while progesterone increased.

Low-density lipoprotein oxidation biomarkers in human health and disease and effects of bioactive compounds.

Based on the significance of oxidized low-density lipoprotein (LDL) in health and disease, this review focuses on human studies addressing oxidation of LDL, including three lines of biomarkers, (i) ex vivo LDL resistance to oxidation, a "challenge test" model, (ii) circulating oxidized LDL, indicating the "current in vivo status", and (iii) autoantibodies against oxidized LDL as fingerprints of an immune response to oxidized LDL, along with circulating oxysterols and 4-hydroxynonenal as biomarkers of lipid peroxidation. Lipid peroxidation and oxidized LDL are hallmarks in the development of various metabolic, cardiovascular and other diseases. Changes further occur across life stages from infancy to older age as well as in athletes and smokers.

Circulating leptin and NF-κB activation in peripheral blood mononuclear cells across the menstrual cycle.

Using the menstrual cycle as a model, this study focused on longitudinal changes and associations within a physiological network known to play a role in female fertility, including, as biologically active nodes, NF-κB, leptin and adiponectin, β-carotene, adipose tissue, and progesterone. In 28 women, leptin, adiponectin, β-carotene, and progesterone concentrations, NF-κB p65 and p50 activation in peripheral blood mononuclear cells (known to possess estrogen, progesterone and leptin receptors), total body fat (TBF) and subcutaneous adipose tissue (SAT) mass were determined at early (T1) and late follicular (T2) and mid (T3) and late (T4) luteal phase. Leptin and adiponectin concentrations were higher, while NF-κB p65 activation was lower at T3 compared with T1.

Increased DNA dicarbonyl glycation and oxidation markers in patients with type 2 diabetes and link to diabetic nephropathy.

Aim: The aim of this study was to assess the changes of markers of DNA damage by glycation and oxidation in patients with type 2 diabetes and the association with diabetic nephropathy.

Methodology: DNA oxidation and glycation adducts were analysed in plasma and urine by stable isotopic dilution analysis liquid chromatography-tandem mass spectrometry. DNA markers analysed were as follows: the oxidation adduct 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-OxodG) and glycation adducts of glyoxal and methylglyoxal--imidazopurinones GdG, MGdG, and N2-(1,R/S-carboxyethyl)deoxyguanosine (CEdG).

Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy.

Background: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273).

Effects of a pre-dialysis patient education program on the relative frequencies of dialysis modalities.

Background: Pre-dialysis education can guide the choice of the dialysis modality best tailored to meet the needs and preferences of individual patients with chronic kidney disease.

Methods: In a retrospective single-center cohort study, we evaluated the impact of a pre-dialysis education program on the incidence rates of patients using hemodialysis (HD) and peritoneal dialysis (PD) in our unit. The frequency distribution of dialysis modalities between people attending our education program and people not attending the program (control group) was analyzed for the 4-year period 2004 - 2008.

Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy.

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers.

Urinary collagen fragments are significantly altered in diabetes: a link to pathophysiology.

Background: The pathogenesis of diabetes mellitus (DM) is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes.

Exit-site care in Austrian peritoneal dialysis centers -- a nationwide survey.

Background: Catheter-associated infections markedly contribute to treatment failure in peritoneal dialysis (PD) patients. There is much controversy surrounding prophylactic strategies to prevent these infections.

Methods: In this nationwide multicenter study we analyzed strategies to prevent catheter-associated infections as performed in Austrian PD centers in 2006.

Antioxidant status of patients on peritoneal dialysis: associations with inflammation and glycoxidative stress.

Background: Patients on peritoneal dialysis (PD) frequently exhibit oxidant-antioxidant imbalance, advanced glycation end-product overload, and subclinical inflammation but the interrelations between these pathophysiological changes have not been fully elucidated.

Subjects And Methods: To study possible associations, a cross-sectional study of antioxidant status, glycoxidative stress, and inflammation, using HPLC and ELISA methods, was undertaken in 37 PD patients and age- and sex-matched healthy controls.

Results: Plasma ascorbate concentrations were low in patients not taking at least low-dose vitamin C supplements.

Increased concentrations of circulating vitamin E in carriers of the apolipoprotein A5 gene - 1131T>C variant and associations with plasma lipids and lipid peroxidation.

The aim of this study was to investigate the effects of the apolipoprotein A5 (APOA5) 1131T>C gene variant on vitamin E status and lipid profile. The gene variant was determined in 297 healthy nonsmoking men aged 20-75 years and recruited in the VITAGE Project. Effects of the genotype on vitamin E in plasma, LDL, and buccal mucosa cells (BMC) as well as on cholesterol and triglyceride (TG) concentrations in plasma and apolipoprotein A-I (apoA-I), apoB, apoE, apoC-III, and plasma fatty acids were determined.

Reference values for plasma concentrations of asymmetrical dimethylarginine (ADMA) and other arginine metabolites in men after validation of a chromatographic method.

Background: Owing to the growing number of reports in the literature on ADMA as a possibly useful marker of endothelial health, its use in the clinical laboratory is of increasing interest. Age dependency and the small, but statistically significant differences between healthy subjects and disease groups are difficult to interpret. Additionally, levels of ADMA in comparable patient groups of different studies vary widely, even when similar methods have been used.

[Comparison of clinical outcomes in peritoneal dialysis and hemodialysis].

In addition to kidney transplantation, peritoneal dialysis (PD) and hemodialysis represent two options for renal replacement therapy in patients with end-stage renal disease (ESRD). Given that most patients are suitable for both types of dialysis and that many of them require lifelong therapy, differences in clinical outcome between these treatments are of major interest. Differences between the two dialysis treatments have been described in single clinical aspects (e.

Does aging affect the response of vitamin E status to vitamin E depletion and supplementation?

A vitamin E depletion/supplementation study was conducted in 100 healthy 20-75-year-old volunteers. The responses of vitamin E status to 3-week dietary vitamin E restriction to approximately 25% of recommended intake and 2-month unrestricted dietary intake plus 800 IU/d of RRR-alpha-tocopherol were studied as a function of age. Plasma alpha-tocopherol concentrations were closely related to cholesterol concentrations, which increased with age (P < 0.

The decrease in gamma-tocopherol in plasma and lipoprotein fractions levels off within two days of vitamin E supplementation.

The effects of vitamin E supplementation on alpha- and gamma-tocopherol concentrations were studied in plasma and lipoprotein fractions of five healthy volunteers taking 1000 IU/day of RRR alpha-tocopherol for 4 days. Although plasma alpha-tocopherol increased, gamma-tocopherol decreased. Compared with baseline, gamma-/alpha-tocopherol ratios decreased from 48 h onward (P < 0.

Effects of vitamin E depletion/repletion on biomarkers of oxidative stress in healthy aging.

The effects on ex vivo LDL resistance to oxidation and biomarkers of in vivo oxidative stress in response to 3-month dietary vitamin E restriction to 25% of recommended intake and 2-month unrestricted dietary intake and supplementation with 800 IU/d were studied in 100 healthy, nonsmoking 20-75-year-old volunteers. Significant changes in vitamin E status were associated with decreases and increases, respectively, in LDL resistance to oxidation in the depletion and supplementation period and with decreases in lipid peroxidation and oxidative DNA modification in the supplementation period. Healthy aging was not associated with enhanced susceptibility to oxidation in the depletion period.

The effect of age on vitamin E status, metabolism, and function: metabolism as assessed by labeled tocopherols.

The effects of age on vitamin E metabolism were studied in 97 healthy 20-75-year-old male nonsmoking Austrian volunteers of the VITAGE project. After a single oral intake of 30 mg d(6)-RRR-alpha- and d(2)-RRR-gamma-tocopheryl acetate, blood and 24-hour urine was collected. Deuterated tocopherols in plasma and deuterated urinary metabolites were analyzed by GC-MS.

Effects of vitamin E and carotenoid status on oxidative stress in health and disease. Evidence obtained from human intervention studies.

Vitamin E and carotenoids are known to act as antioxidants both in vitro and in vivo. In this review we present a series of studies in healthy subjects and in patients who exhibit either acute or chronic oxidative stress. In the EU-Commission funded VITAGE project we investigated the status and effects of vitamin E and carotenoids on oxidative stress in 300 healthy volunteers.

Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis.

Intravenous iron application to anemic patients on hemodialysis leads to an "oversaturation" of transferrin. As a result, non-transferrin-bound, redox-active iron might induce lipid peroxidation. To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(III) hydroxide sucrose complex intravenously during a hemodialysis session, 22 patients were investigated in a randomized cross-over design, either with or without a single oral dose of 1200 IU of all-rac-alpha-tocopheryl acetate taken 6 h before the hemodialysis session.