[show abstract][hide abstract] ABSTRACT: 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).
In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier.
We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found.
We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.
[show abstract][hide abstract] ABSTRACT: Oxidative stress is a risk factor for chronic diseases and was previously shown to be independently associated with obesity. The authors investigated the relationship between body mass index (BMI), age and oxidative stress on 2190 subjects undergoing a health care examination. Total antioxidant status (TAS), total peroxides (TOC) and autoantibodies against oxidized LDL (oLAb) were used as oxidative stress biomarkers in addition to serum lipoproteins, bilirubin and uric acid. Gender-specific differences were observed for age, BMI, serum concentrations of bilirubin, low-density lipoprotein (LDL), uric acid and TAS, all of which were higher in males (p < 0.001), while high-density lipoprotein (HDL), HDL/LDL ratio and TOC were higher in females (p < 0.001). Total cholesterol (p < 0.05) and LDL were increased (p < 0.05), while HDL was decreased (p < 0.05) in overweight and obese subjects. This was accompanied by increased uric acid and TAS concentrations. Lowest oLAb titers were detected in obese subjects. In extremely obese subjects, increased TOC and decreased TAS were observed in spite of high uric acid levels. These results demonstrate that oxidative stress increases with increasing BMI and age, as a sequel to an impaired antioxidant status, the consumption of oLAbs, an increase of peroxides and uric acid and a disadvantaged lipid profile.
The Aging Male 04/2012; 15(3):159-65. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Glyoxal and methylglyoxal are reactive dicarbonyl metabolites formed and metabolized in physiological systems. Increased exposure to these dicarbonyls is linked to mutagenesis and cytotoxicity and enhanced dicarbonyl metabolism by overexpression of glyoxalase 1 is linked to tumour multidrug resistance in cancer chemotherapy. We report herein that glycation of DNA by glyoxal and methylglyoxal produces a quantitatively important class of nucleotide adduct in physiological systems-imidazopurinones. The adduct derived from methylglyoxal-3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one isomers-was the major quantitative adduct detected in mononuclear leukocytes in vivo and tumour cell lines in vitro. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell permeable glyoxalase 1 inhibitor. Unexpectedly, the DNA content of methylglyoxal-derived imidazopurinone and oxidative marker 7,8-dihydro-8-oxo-2'-deoxyguanosine were increased moderately in glyoxalase 1-linked multidrug resistant tumour cell lines. Together these findings suggest that imidazopurinones are a major type of endogenous DNA damage and glyoxalase 1 overexpression in tumour cells strives to counter increased imidazopurinone formation in tumour cells likely linked to their high glycolytic activity.
Nucleic Acids Research 09/2010; 38(16):5432-42. · 8.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D) or type 2 diabetes (T2D).
Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n = 299) or T2D (n = 288), was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced) previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n = 382) from control subjects (n = 315) with 94% (95% CI: 92-95) accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n = 68) and T2D (n = 42) was employed, enabling identification of 131 biomarker candidates (40 were sequenced) differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n = 108) with 88% (95% CI: 81-94%) accuracy, and in patients with impaired renal function (n = 369) with 85% (95% CI: 81-88%) accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed.
These findings, based on the largest proteomic study performed to date on subjects with DM, validate the previously described biomarkers for DM, and pinpoint differences in the urinary proteome of T1D and T2D, indicating significant differences in extracellular matrix remodeling.
[show abstract][hide abstract] ABSTRACT: 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. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration ≥5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82).
Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients.
These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin.
PLoS ONE 01/2010; 5(10):e13421. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intestinal permeability describes non-carrier-mediated modes of transport through the intestinal epithelium. Wrist-ankle bioimpedance analysis (BIA) is a standard method to determine body composition based on the measurements of whole-body electrical resistance and reactance values. The present report deals with the coincidentally observed associations between permeability results and electrical raw values of BIA and their subsequent reproduction in a larger group of individuals.
Tetrapolar wrist-ankle BIA was performed on day 1 in the initial sample (12 women, 36 +/- 11 y of age) and the validation sample (36 healthy subjects, 26 women and 10 men, 35 +/- 14 y of age). Intestinal permeability tests (lactulose and mannitol) were implemented within 1 wk thereafter. Wrist-ankle electrical resistance plus electrical resistance between current-conducting electrodes and voltage-sensing electrodes (Rtotal) was measured at 5 kHz and 100 kHz.
Permeability and bioimpedance raw values were normal, indicating normal tight junction permeability and normal hydration. Lactulose correlated to R(50total) in the initial sample (rho = 0.639, P = 0.025) and in the validation sample (rho = 0.673, P < 0.001). Weaker associations to R(50total) were observed with mannitol (rho = 0.381, P = 0.008) and lactulose/mannitol (rho = 0.369, P = 0.010) in the total group of individuals. Regression analyses demonstrated that R(50total) alone accounted for 41.3% of the variance in lactulose permeability.
The nature of the observed positive association between intestinal tight junction permeability and whole-body electrical resistance is unclear. We hypothesize that regulation involving submolecular mechanisms based on the principles of quantum physics might have caused the observed association. Such coherent mechanisms might possibly play a role in basal physiologic regulation in humans.
[show abstract][hide abstract] ABSTRACT: 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.
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.
Plasma ascorbate concentrations were low in patients not taking at least low-dose vitamin C supplements. In patients taking vitamin C supplements, there was a positive relation between ascorbate and pentosidine concentrations. Vitamin E and carotenoid concentrations were comparable between patients and controls, while lycopene and lutein/zeaxanthin concentrations were lower. Interleukin-6, C-reactive protein (CRP), and pentosidine concentrations were elevated in PD patients. beta-Cryptoxanthin, lycopene, and lutein/zeaxanthin concentrations were inversely related to interleukin-6 concentrations. beta-Cryptoxanthin concentrations were also inversely related to CRP concentrations. Pentosidine showed a low dialysate-to-plasma ratio, indicating low peritoneal clearance. Pentosidine concentrations increased with duration of PD therapy, while alpha- and beta-carotene concentrations decreased. Malondialdehyde concentrations were elevated compared to controls but remained within the normal range. Retinol concentrations decreased with PD therapy and were inversely related to interleukin-6 and CRP concentrations.
Low-dose vitamin C supplements and a carotenoid-rich diet should be recommended for PD patients to maintain normal antioxidant status and efficiently counteract the chronic inflammatory response, rather than high doses of vitamin C, which could play a role as a precursor of pentosidine.
Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis 02/2009; 29(1):89-101. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adipokines are fat-derived hormones and cytokines with immune-modulating and metabolic properties. Most of them are associated with insulin resistance. The aim of the present investigation was to evaluate circulating levels of adipokines and glucose homeostasis in patients with inflammatory bowel disease (IBD) and to evaluate possible associations with the course and characteristics of the disease.
Serum leptin, resistin, visfatin, retinol-binding protein-4, adiponectin, glucose, insulin, and inflammatory parameters were analyzed in 93 patients with inactive IBD (49 with Crohn's disease [CD], 44 with ulcerative colitis [UC]), 35 patients with active IBD (18 with CD, 17 with UC), and 37 age- and body mass index-matched healthy controls. Ninety-two patients were followed for 6 mo.
Leptin was similar in patients with IBD and controls, whereas resistin and visfatin were increased in patients with active disease but not in those in remission. In active and inactive disease, adiponectin was decreased (P < 0.001) and retinol-binding protein-4 was increased (P < 0.001) compared with controls. About 60% of patients with IBD showed increased levels of insulin, whereas serum glucose remained normal, resulting in increased homeostasis model assessment values in most patients. Hyperinsulinemia was associated with the decrease in adiponectin (r = -0.572, P < 0.001) and proved to be an independent protective factor for 6-mo maintenance of remission (P = 0.016).
IBD led to largely similar alterations in circulating adipokines and hyperinsulinemia in patients with CD and those with UC. The unexpected protective effect of hyperinsulinemia on relapse rate denotes the role of the metabolic-inflammatory response as a modulator in IBD.
[show abstract][hide abstract] ABSTRACT: Zinc deficiency is common among the elderly and has been associated with oxidative stress, immune dysfunction and CVD. We examined whether low zinc concentrations are associated with total, cardiovascular and non-cardiovascular mortality. Serum zinc concentrations were measured in 3316 patients from the Ludwigshafen Risk and Cardiovascular Health study, who were routinely referred to coronary angiography at a single tertiary care centre in Southwest Germany. After a median follow-up period of 7.75 years, 769 patients had died, including 484 deaths due to cardiovascular and 261 due to non-cardiovascular causes. After adjustments for cardiovascular risk factors and other possible confounders, the hazard ratios in the first when compared with the fourth zinc quartile, and per quartile decrease were 1.44 (95 % CI 1.13, 1.83; P = 0.001) and 1.15 (95 % CI 1.07, 1.24; P < 0.001) for total mortality, 2.20 (95 % CI 1.42, 3.42; P < 0.001) and 1.32 (95 % CI 1.16, 1.50; P < 0.001) for non-cardiovascular mortality and 1.24 (95 % CI 0.92, 1.66; P = 0.162) and 1.10 (95 % CI 1.01, 1.21; P = 0.038) for cardiovascular mortality. Furthermore, serum zinc concentrations correlated negatively with age and markers of inflammation and positively with antioxidants. The present results suggest that zinc deficiency may contribute to a reduced life expectancy in patients scheduled for coronary angiography.
The British journal of nutrition 10/2008; 101(10):1534-40. · 3.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Neopterin is released from human monocyte-derived macrophages upon stimulation with interferon-gamma and is a sensitive indicator for cellular immune activation. Furthermore, reactive oxygen species (ROS) are produced in case of immune activation and inflammation. In a cross-sectional approach, plasma concentrations of neopterin and of antioxidant compounds and vitamins were compared in 1463 patients investigated by coronary angiography, which were recruited within the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. Serum neopterin concentrations were higher in patients with coronary artery disease (CAD; mean+/-S.D.: 8.7+/-7.3 nmol/L) compared to controls (7.4+/-5.0 nmol/L; Welch's t-test: p<0.001). Mean concentrations of ascorbic acid (p<0.0001), gamma-tocopherol (p<0.05), lycopene (p<0.001), lutein+zeaxanthin (p<0.05), alpha-carotene (p<0.05) and beta-carotene (p<0.05) were lower in CAD than in controls. Neopterin concentrations correlated with CAD-score (r(s)=0.156; p<0.0001) and inversely with antioxidants lycopene (r(s)=-0.277; p<0.0001) and lutein+zeaxanthin (r(s)=-0.175; p<0.0001) levels and with vitamins ascorbic acid (r(s)=-0.207; p<0.0001) and alpha-tocopherol (r(s)=-0.105; p<0.0001). The study demonstrates that higher neopterin production is associated with lower concentrations of antioxidant compounds in patients at risk for atherosclerosis. Results suggest that lower concentrations of antioxidant compounds may relate to higher grade of chronic immune activation in patients.
[show abstract][hide abstract] ABSTRACT: Introduction
The retinoic acid (RA) signaling pathway regulates the transcription of target genes which control lipid metabolism mediated by the ligand of the nuclear receptors, retinoic X receptor and RA receptor, and the cofactor cellular RA binding protein-II. Interestingly, this signaling pathway has been associated with disorders of lipid metabolism such as familial combined hyperlipidemia (FCHL) and the hyperlipidemia secondary to antiretroviral HIV treatment with protease inhibitors (PI). We sought evidence for the hypothesis that the CRABP2 gene is involved in the regulation of lipid metabolism.
Subjects and methods
We performed association studies using the promoter –394T>C polymorphism of the CRABP2 gene in 3 different cohorts (299 healthy males, 182 HIV-infected patients and 151 patients with familial hypercholesterolemia [FH]). All cholesterol measurements were in the absence of any lipid lowering agents. ANOVA was performed on the data adjusted for age, BMI, gender and PI use.
The frequency of the C allele was 0.03 in the 3 groups. Among healthy males, carriers of the C allele had 9% higher total plasma cholesterol (p = 0.027) and 13% higher LDLc concentrations (p = 0.020). In HIV-infected patients, a multivariate analysis of 4 measurements over a one year period showed that carriers of the C allele had significantly higher LDLc of between 10 and 31% (p = 0.001) compared with non-carriers of the allele. FH patients who were carriers of the C allele had a 16% increase in LDLc (p = 0.038). The C allele was significantly over-represented among hypercholesterolemic patients (p = 0.001).
Our results show that the CRABP2 gene, a member of the retinoid signaling pathway, is associated with increased plasma LDLc concentrations.
Clínica e Investigación en Arteriosclerosis. 04/2008; 20(2).
[show abstract][hide abstract] ABSTRACT: Data regarding the nutritional status, antioxidant compounds and plasma fatty acid (FA) composition in inactive IBD are conflicting. We compared plasma levels of antioxidants and FA of patients with inactive IBD with active IBD and controls.
Plasma levels of vitamin C, vitamin E, carotenoids, saturated, monounsaturated and polyunsaturated FA, inflammatory markers and nutritional status were determined after an overnight fast in 132 patients with quiescent IBD (40.6+/-13.2 years, 87F/45M), 35 patients with active disease (37.9+/-12.1 years, 25F/10M) and 45 age- and BMI-matched healthy controls (38.1+/-10.5 years, 39F/6M). Results are expressed as mean+/-SD or median [25th percentile;75th percentile].
Body mass index (BMI) was normal in inactive (23.9+/-4.7 kg/m(2)), active IBD (22.7+/-4.2 kg/m(2)) and controls (22.3+/-1.9 kg/m(2)). Compared with controls patients with quiescent IBD showed significantly decreased plasma levels of carotenoids (1.85 [1.37;2.56] vs 1.39 [0.88;1.87] micromol/L) and vitamin C (62.3 [48.7;75.0] vs 51.0 [36.4;77.6] micromol/L), increased levels of saturated FA (3879 [3380;4420] vs 3410 [3142;3989] micromol/L) and monounsaturated FA (2578 [2258;3089] vs 2044 [1836;2434] micromol/L) and similar levels of vitamin E and polyunsaturated FA. Results in active disease were similar to inactive disease.
This study shows that antioxidant status and FA profile in a larger population of IBD patients are disturbed independently from disease activity and despite normal overall nutritional status.
[show abstract][hide abstract] ABSTRACT: We investigated competitive- and long-term oxidative stress during a competition season in eight top-ranked members of the Austrian Men's Alpine Ski Team. Serum total peroxides, antibody titers against oxidized LDL (oLAb) and lag time of the degradation of the fluorophore 1-palmitoyl-2-((2-(4-(6-phenyl-trans-1,3,5-hexatrienyl)phenyl)ethyl)-carbonyl)-sn-glycero-3-phosphocholine were measured, along with plasma concentrations of ascorbate, alpha- and gamma-tocopherol, beta-carotene, uric acid and the lipid status. Competitive stress was indicated through an increased post-race uric acid level (286 +/- 50 microM pre-race vs 456 +/- 77 microM post-race, P<0.001) in December. Long-term effects were already apparent in November, with the highest concentrations of total peroxides (680 +/- 458 microM H(2)O(2) equivalents vs December 47 +/- 58 microM H(2)O(2) equivalents and January 15 +/- 28 microM H(2)O(2) equivalents, P<0.001) and a concomitant decrease in oLAb titers with an antibody trough in December (439 +/- 150 mU/mL vs baseline 1036 +/- 328 mU/mL; P=0.003). In January, after recovery, they attained nearly pre-season levels of oxidative stress biomarkers. This study indicates midseason oxidative stress in top-level skiers, which was associated with the performance in these athletes.
Scandinavian Journal of Medicine and Science in Sports 02/2008; 19(2):206-12. · 3.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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. Plasma malondialdehyde concentrations as a marker of in vivo lipid peroxidation were determined. C allele carriers showed significantly higher TG, VLDL, and LDL in plasma, higher cholesterol in VLDL and intermediate density lipoprotein, and higher plasma fatty acids. Plasma alpha-tocopherol (but not gamma-tocopherol, LDL alpha- and gamma-tocopherol, or BMC total vitamin E) was increased significantly in C allele carriers compared with homozygote T allele carriers (P = 0.02), but not after adjustment for cholesterol or TG. Plasma malondialdehyde concentrations did not differ between genotypes. In conclusion, higher plasma lipids in the TC+CC genotype are efficiently protected against lipid peroxidation by higher alpha-tocopherol concentrations. Lipid-standardized vitamin E should be used to reliably assess vitamin E status in genetic association studies.
The Journal of Lipid Research 11/2007; 48(11):2506-13. · 4.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
After analytical evaluation of a chromatographic method according to international guidelines, we analysed asymmetrical (ADMA) and symmetrical dimethyl arginine (SDMA), homo-arginine and arginine in EDTA plasma of 292 healthy males aged 20 to 75 years (y) who had passed strict inclusion/exclusion criteria. For statistical analysis, 4 age groups were formed. Group differences were identified with the non-parametric Kruskal-Wallis test.
Calibration curves were linear throughout the selected ranges; the standard deviation for the regression line, recovery, imprecision, and accuracy results were all highly satisfactory. The reference ranges of ADMA for the 4 age groups are presented as age (mean+/-SD of age group, y); number of subjects; median, 2.5th-97.5th percentile: group <35 y: 26.7+/-4.0 y; n=78; 0.58, 0.43-0.69 micromol/L; group 35-49 y: 41.6+/-4.0 y; n=93; 0.59, 0.45-0.73 micromol/L; group 50-65 y: 57.5+/-4.2 y; n=82; 0.61, 0.46-0.78 micromol/L; and group >65 y: 69.6+/-3.3 y; n=39; 0.64, 0.54-0.79 micromol/L.
Only highly precise methods are able to detect small differences between groups. The application of an evaluated method to a well defined group of healthy subjects should provide a basis for comparison of ADMA concentrations in different patient populations of future studies.
[show abstract][hide abstract] ABSTRACT: Background Only few data are available about the plasma fatty acid (FA) profile as well as antioxidant vitamins in inactive IBD compared with active IBD patients and healthy controls (HC). Methods To obtain a detailed overview of antioxidant vitamins and FA we analysed vitamin C, vitamin E, carotenoids (lycopene, lutein/zeaxanthin, β-cryptoxanthin, -/β-carotene), saturated (SFA, C14:0, C15:0, C16:0, C18.0, C20:0, C22:0), mono-unsaturated (MUFA, C16:1n7, C18:1n7, C18:1n9, C22:1n9) and poly-unsaturated FA (PUFA, C18:2n6, C18:3n6, C20:3n6, C20:4n6, C22:4n6, C18:3n3, C20:5n3, C20:6n3, C22:5n3, C22:6n3) in plasma. Inflammatory parameters (CRP; a-1-acid glycoprotein, AAG; faecal calprotectin, FC) as well as clinical disease activity (CDAI, CAI) were determined in 167 IBD patients and 45 age and BMI matched HC. The IBD study groups consisted of 138 inactive IBD (83 Crohn’s disease, CD, 49 ulcerative colitis, UC) and 35 active IBD patients (17 CD, 18 UC). Results Overall nutritional status was normal in inactive (BMI 23.9±4.7kg/m2), active (22.7±4.2 kg/m2) IBD patients and HC (22.3±1.9kg/m2). Inflammatory parameters (CRP, AAG, FC) were significantly increased in inactive and active IBD in comparison to HC. Plasma levels of carotenoids differed significantly between inactive and active IBD as well as between inactive/active IBD and HC (table). Significantly decreased plasma levels of vitamin C, increased levels of MUFA and comparable levels of vitamin E, SFA and PUFA have been found between inactive/active IBD and HC. FA inversely correlated with FC, vitamin C and total carotenoids were found to inversely correlate with FC, CRP and AAG in IBD patients.
Discussion This study showed for the first time that antioxidant status and FA profile in a large population of inactive and active IBD patients are disturbed independently from disease activity as compared to matched HC, despite normal overall nutritional status. The compromised status of antioxidant vitamins might offer a therapeutic opportunity to improve antioxidant and inflammatory status.
[show abstract][hide abstract] ABSTRACT: Data on vitamin E content of foods are essential for nutrition research and its application. The aim of this study was to investigate the precision of calculated vitamin E content of prepared meals.
The vitamin E content of 69 dishes of a menu cycle sampled at two occasions were calculated using 4 different food composition tables (FCT) and measured by HPLC.
Data were complete for 50-69 dishes. The proportion of dishes with differences between FCTs < or = 20% were 17-100%. Differences between HPLC and the Souci-Fachmann-Kraut table were < or = 20% in 8/46 dishes for alpha- and in 14/46 dishes for gamma-tocopherol. Differences fell in the order of baked > raw > fried/roasted > boiled > mixed prepared foods. The 2 samplings taken 6 months apart showed considerable differences.
There are substantial differences in calculated/measured vitamin E content of prepared foods: (i) between different FCTs; (ii) between FCTs and HPLC, and (iii) between different seasons. This can be explained by intrinsic variability (breeding, season, country of origin, ripeness, freshness) and food processing, as well as selection of FCTs and should be taken into account when interpreting data of dietary intervention studies.
[show abstract][hide abstract] ABSTRACT: The cellular retinoic acid-binding protein II (CRABP-II), together with nuclear receptors such as the retinoid X receptor (RXR) and retinoic acid receptor (RAR), is involved in the transcriptional regulation of genes that control lipid metabolism via the retinoid signaling pathway and, as such, may be associated with disorders of lipid metabolism. Interestingly, the gene for CRABP-II is located on chromosome 1q21-23, which is a region that has been linked with disorders such as familial combined hyperlipidemia (FCHL), type 2 diabetes mellitus, and partial lipodystrophy, all of which are characterized by dyslipidemia.
We investigated the hypothesis that the CRABP2 gene is involved in the regulation of lipid metabolism. Using the promoter -394T>C polymorphism of the CRABP2 gene, we performed association studies in three different cohorts: 299 healthy males, 182 HIV-infected patients and 151 patients with familial hypercholesterolemia (FH). All cholesterol measurements were performed in the absence of any lipid-lowering agents. ANOVA was performed on data adjusted for age, body mass index (BMI), gender, and use of protease inhibitors.
The frequency of the C allele was 0.03 in the three groups. Among healthy males, carriers of the C allele had 9% higher total plasma cholesterol (p=0.027) and 13% higher low-density lipoprotein cholesterol (LDL-C) concentrations (p=0.020). In HIV-infected patients, multivariate analysis of four measures over a 1-year period showed that carriers of the C allele had significantly higher LDL-C of between 10% and 31% (p=0.001) compared with non-carriers of the allele. FH patients who were carriers of the C allele had 16% higher LDL-C (p=0.038). The C allele was significantly over-represented among hypercholesterolemic patients (p=0.001).
Our results show that the CRABP2 gene, a member of the retinoid signaling pathway, is associated with increased plasma LDL-C concentrations.
Clinical Chemistry and Laboratory Medicine 02/2007; 45(5):615-20. · 3.01 Impact Factor
[show abstract][hide abstract] ABSTRACT: The regulation of cell growth and differentiation and also expression of a number of genes by retinoids are mediated by nuclear retinoid receptors (RARs and/or RXRs). In this study we investigated age-related alteration in both RAR and RXR receptor subtypes gene expression and tissue transglutaminase (tTG) activity before and after supplementation with 13-cis retinoic acid (13cRA) in human peripheral blood mononuclear cells (PBMCs). Healthy men (40) were divided in two groups according to their age (young group: 26.1+/-4.1 years and old group: 65.4+/-3.8 years). Each volunteer received 13cRA (Curacné), 0.5mg/(kgday)) during a period of 4 weeks. We have shown that RXRbeta expression was decreased significantly (p=0.0108) in PBMCs of elderly men when compared to that of young volunteers. Distribution of retinoic acid receptor subtype expression in PBMCs was found in the order: RXRbeta>RARgamma>RXRalpha>RARalpha. The tTG activity in PBMCs reflected a trend to be enhanced after 13-cis retinoic acid supplementation. In conclusion, we demonstrate a significant decrease in the expression of RXRbeta subtype of rexinoid receptors in PBMCs of healthy elderly men. Our data suggest that in healthy elderly men reduction of RXRbeta expression in PBMCs might be a common feature of physiological senescence.
Mechanisms of Ageing and Development 01/2007; 128(11-12):594-600. · 3.26 Impact Factor