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Background Because of its high cardiospecificity, cardiac troponin T (cTnT) is one of the first-choice biomarkers to diagnose acute myocardial infarction (AMI). cTnT is extensively fragmented in serum of patients suffering from AMI. However, it is currently unknown whether all cTnT is completely degraded in the body or whether some cTnT fragments can leave the body via urine. The aim of the present study is to develop a method for the detection of cTnT in urine and to examine whether cTnT is detectable in patient urine. Methods Proteins in urine samples of 20 patients were precipitated using a cTnT-specific immunoprecipitation technique and a nonspecific acetonitrile protein precipitation. After in-solution digestion of the precipitated proteins, the resulting peptides were separated and analyzed using HPLC and mass spectrometry with a targeted selected ion monitoring assay with data-dependent tandem mass spectrometry (t-SIM/dd-MS2). Results The t-SIM/dd-MS2 assay was validated using a synthetic peptide standard containing 10 specific cTnT peptides of interest and with purified human intact cTnT spiked in urine from healthy individuals. Using this assay, 6 different cTnT-specific peptides were identified in urine samples from 3 different patients, all suffering from AMI. Conclusions We show here for the first time that cTnT can be present in the urine of AMI patients using a targeted LC-MS/MS assay. Whether the presence of cTnT in urine reflects a physiological or pathophysiological process still needs to be elucidated.

Background High-sensitivity cardiac troponin (hs-cTn) assays have reduced specificity for myocardial infarction (MI). In conditions other than MI, cardiac troponin T (cTnT) elevations have been attributed to small cTnT fragments. In search of improved cTnT assay specificity for MI, determination of the in-vivo molecular appearance of cTnT during MI is pivotal. Purpose To determine cTnT composition close to its site of release and during the course of MI by multi-site coronary venous system (CVS) and peripheral sampling. Methods Lithium-heparinized (LH) plasma and serum samples were obtained from multiple CVS locations in NSTEMI patients. Additionally, samples were drawn from a peripheral artery and vein followed by collections at 6- and 12 hours post-catheterization. cTnT concentrations were measured using the hs-cTnT immunoassay (Roche). The molecular cTnT composition was determined by gel filtration chromatography and Western blotting in an early and late presenting patient. Results CVS hs-cTnT concentrations were 28% higher than in the peripheral artery sample (n=71, p Central illustration Conclusions In NSTEMI, cTnT is released as a combination of cTn T-I-C complex, free intact cTnT and multiple cTnT fragments. Over time, the composition of observed cTnT forms changes due to in-vivo degradation. These findings serve as a stepping stone to improve diagnostic accuracy of the hs-cTnT assay for MI.

Background Cardiac troponin T ( cTnT ) is seen in many other conditions besides myocardial infarction, and recent studies demonstrated distinct forms of cTnT . At present, the in vivo formation of these different cTnT forms is incompletely understood. We therefore performed a study on the composition of cTnT during the course of myocardial infarction, including coronary venous system sampling, close to its site of release. Methods and Results Baseline samples were obtained from multiple coronary venous system locations, and a peripheral artery and vein in 71 non– ST ‐segment–elevation myocardial infarction patients. Additionally, peripheral blood was drawn at 6‐ and 12‐hours postcatheterization. cTnT concentrations were measured using the high‐sensitivity‐ cTnT immunoassay. The cTnT composition was determined via gel filtration chromatography and Western blotting in an early and late presenting patient. High‐sensitivity ‐ cTnT concentrations were 28% higher in the coronary venous system than peripherally (n=71, P cT n T‐I‐C complex, free intact cTnT , and 29 kD a and 15 to 18 kD a cTnT fragments, all in higher concentrations than in simultaneously obtained peripheral samples. While cT n T‐I‐C complex proportionally decreased, and disappeared over time, 15 to 18 kD a cTnT fragments increased. Moreover, cT n T‐I‐C complex was more prominent in the early than in the late presenting patient. Conclusions This explorative study in non– ST ‐segment–elevation myocardial infarction shows that cTnT is released from cardiomyocytes as a combination of cT n T‐I‐C complex, free intact cTnT , and multiple cTnT fragments indicating intracellular cTnT degradation. Over time, the cT n T‐I‐C complex disappeared because of in vivo degradation. These insights might serve as a stepping stone toward a high‐sensitivity‐ cTnT immunoassay more specific for myocardial infarction.

Background: The age-related decline in skeletal muscle mass is partly attributed to anabolic resistance to food intake. Dietary protein ingestion before sleep could be used as a nutritional strategy to compensate for anabolic resistance. Objective: The present study assessed whether physical activity performed in the evening can augment the overnight muscle protein synthetic response to presleep protein ingestion in older men. Methods: In a parallel group design, 23 healthy older men (mean SEM age: 71 1 y) were randomly assigned to ingest 40 g protein intrinsically labeled with L[1-C-13]-phenylalanine and L-[1-C-13]-leucine before going to sleep with (PRO+EX) or without (PRO) performing physical activity earlier in the evening. Overnight protein digestion and absorption kinetics and myofibrillar protein synthesis rates were assessed by combining primed, continuous infusions of L-[ring-H-2(5)]-phenylalanine, L-[1-C-13]-leucine, and L-[ring-H-2(2)]-tyrosine with the ingestion of intrinsically labeled casein protein. Muscle and blood samples were collected throughout overnight sleep. Results: Protein ingested before sleep was normally digested and absorbed, with 54% +/- 2% of the protein-derived amino acids appearing in the circulation throughout overnight sleep. Overnight myofibrillar protein synthesis rates were 31 % (0.058% +/- 0.002%/h compared with 0.044% +/- 0.003%/h; P

Cardiac troponin T (cTnT) fragmentation in human serum was investigated using a newly developed targeted selected ion monitoring assay, as described in the accompanying article: "Development of a targeted selected ion monitoring assay for the elucidation of protease induced structural changes in cardiac troponin T" W. This article presents data describing aspects of the validation and optimisation of this assay. The data consists of several figures, an excel file containing the results of a sequence identity search, and a description of the raw mass spectrometry (MS) data files, deposited in the ProteomeXchange repository with id PRIDE: PXD003187. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/40).

To the Editor: During acute myocardial infarction (AMI), 1 cardiac troponin T (cTnT) is released from the damaged myocardium. One would expect a strong correlation between concentrations of cTnT measured in the blood after AMI and the extent of myocardial damage. However, various studies have shown a rather moderate correlation between infarct size and cTnT concentrations (1, 2). Frequently considered explanations for this phenomenon are methodological or focused on physiological factors associated with differences in release and elimination of cTnT (2). In contrast, less attention has been paid to the possible presence of inherent factors in the blood, such as (auto)antibodies or proteases, that might modify cTnT or interfere with the assay. We hypothesized that these factors may be ubiquitously present in the general population and might affect the measured concentrations of cTnT in individuals. We measured cTnT, cTnI, creatine kinase MB isoenzyme (CK-MB), and myoglobin concentrations in sera from 24 healthy volunteers (age range 22–54 years) before and after the addition of serum from a patient suffering from AMI (age 59 years, cTnT concentration approximately 19.5 μg/L). All participants gave written informed consent and leftover material was used in accordance with the code of proper secondary use of human tissue …

Background: The loss of skeletal muscle mass with aging has been attributed to the blunted anabolic response to protein intake. Presleep protein ingestion has been suggested as an effective strategy to compensate for such anabolic resistance. Objective: We assessed the efficacy of presleep protein ingestion on dietary protein digestion and absorption kinetics and overnight muscle protein synthesis rates in older men. Methods: In a randomized, double-blind, parallel design, 48 older men (mean ± SEM age: 72 ± 1 y) ingested 40 g casein (PRO40), 20 g casein (PRO20), 20 g casein plus 1.5 g leucine (PRO20+LEU), or a placebo before sleep. Ingestion of intrinsically L-[1-13C]-phenylalanine– and L-[1-13C]-leucine–labeled protein was combined with intravenous L-[ring-2H5]-phenylalanine and L-[1-13C]-leucine infusions during sleep. Muscle and blood samples were collected throughout overnight sleep. Results: Exogenous phenylalanine appearance rates increased after protein ingestion, but to a greater extent in PRO40 than in PRO20 and PRO20+LEU (P < 0.05). Overnight myofibrillar protein synthesis rates (based on L-[ring-2H5]-phenylalanine) were 0.033% ± 0.002%/h, 0.037% ± 0.003%/h, 0.039% ± 0.002%/h, and 0.044% ± 0.003%/h in placebo, PRO20, PRO20+LEU, and PRO40, respectively, and were higher in PRO40 than in placebo (P = 0.02). Observations were similar based on L-[1-13C]-leucine tracer (placebo: 0.047% ± 0.004%/h and PRO40: 0.058% ± 0.003%/h, P = 0.08). More protein-derived amino acids (L-[1-13C]-phenylalanine) were incorporated into myofibrillar protein in PRO40 than in PRO20 (0.033 ± 0.002 and 0.019 ± 0.002 MPE, respectively, P < 0.001) and tended to be higher than in PRO20+LEU (0.025 ± 0.002 MPE, P = 0.06). Conclusions: Protein ingested before sleep is properly digested and absorbed throughout the night, providing precursors for myofibrillar protein synthesis during sleep in healthy older men. Ingestion of 40 g protein before sleep increases myofibrillar protein synthesis rates during overnight sleep. These findings provide the scientific basis for a novel nutritional strategy to support muscle mass preservation in aging and disease. This trial was registered at www.trialregister.nl as NTR3885.

Aim Cardiac troponin I (cTnI) and T (cTnT) are the most important biomarkers in the diagnosis of acute myocardial infarction (AMI). Nevertheless, they can be elevated in the absence of AMI. It is unclear if such elevations represent irreversible cardiomyocyte-damage or leakage from viable cardiomyocytes. Our objective is to evaluate whether cTn is released from viable cardiomyocytes in response to ischemia and to identify differences in the release of cTn and its molecular forms. Methods and results HL-1 cardiomyocytes (mouse) were subjected to ischemia (modeled by anoxia with glucose deprivation). The total contents and molecular forms of cTn were determined in culture media and cell lysates. Cell viability was assessed from the release of lactate dehydrogenase (LDH). Before the release of LDH, the intracellular cTn content in ischemic cells decreased significantly compared to control (52% for cTnI; 23% for cTnT) and was not matched by a cTn increase in the medium. cTnI decreased more rapidly than cTnT, resulting in an intracellular cTnT/cTnI ratio of 25.5 after 24 h of ischemia. Western blots revealed changes in the relative amounts of fragmented cTnI and cTnT in ischemic cells. Conclusions HL-1 cardiomyocytes subjected to simulated ischemia released cTnI and cTnT only in combination with the release of LDH. We find no evidence of cTn release from viable cardiomyocytes, but did observe a significant decrease in cTn content, before the onset of cell death. Intracellular decrease of cTn in viable cardiomyocytes can have important consequences for the interpretation of cTn values in clinical practice.

As liver diseases are a major health problem and especially the incidence of metabolic liver diseases like non-alcoholic fatty liver disease (NAFLD) is rising, the demand for non-invasive tests is growing to replace liver biopsy. Non-invasive tests such as carbon-labelled breath tests can provide a valuable contribution to the evaluation of metabolic liver function. This review aims to critically appraise the value of the (13) C-labelled microsomal breath tests for the evaluation of metabolic liver function, and to discuss the role of cytochrome P450 enzymes in the metabolism of the different probe drugs, especially of aminopyrine. Although a number of different probe drugs have been used in breath tests, the perfect drug to assess the functional metabolic capacity of the liver has not been found. Data suggest that both the (13) C(2) -aminopyrine and the (13) C-methacetin breath test can play a role in assessing the capacity of the microsomal liver function and may be useful in the follow-up of patients with chronic liver diseases. Furthermore, CYP2C19 seems to be an important enzyme in the N-demethylation of aminopyrine, and polymorphisms in this gene may influence breath test values, which should be kept in mind when performing the (13) C(2) -aminopyrine breath test in clinical practice.

Background Abdominal aortic aneurysm (AAA) is a degenerative disease of the abdominal aorta leading to progressive dilatation, intra-luminal thrombus (ILT) formation, and rupture. Understanding the natural history of AAA is essential, because different processes and, therefore, different biomarkers, could be involved at each stage of disease progression. The purpose of the present study was to investigate the relationship between systemic expression of biomarkers of inflammation and extracellular matrix remodeling and aneurysm size in AAA patients. Methods and Results All consecutive patients admitted to the (out-) patient clinic of the surgical department of two large community centers were prospectively included. Patients were divided into three groups based on their aneurysm diameter: small (30–44 mm; n = 59), medium-sized (45–54 mm; n = 64) or large (≥ 55 mm; n = 95) AAA. Linear regression modeling showed that age and serum hsCRP concentration were positively associated, whereas serum HDL and IgG concentrations were negatively associated with aneurysm size. This regression model was corrected for possible bias due to statin use and center of inclusion; and also indicated that in general men have larger aneurysms compared with women. Conclusions Different aneurysm sizes showed different expression pattern of HDL, IgG, and hsCRP. These biomarkers may be useful in predicting AAA progression.

Objective: The aim of the study is to investigate the differential expression of proteins in serum of abdominal aortic aneurysm (AAA) patients in relation to aneurysm size (Dmax) and progression. Methods: Two-dimensional differential in-gel electrophoresis (2D-DIGE) together with tandem mass spectrometry (MS/MS) was used to analyse the serum proteome from patients with small (Dmax 30e54 mm) AAA, either stable (increase Dmax < 5m m year � 1 ; n Z 8) or progressive (increase Dmax �5 mm year � 1 ; n Z 8), and large (Dmax �55 mm; n Z 8) AAA. The identified proteins were quantitatively validated in a larger population (n Z 80). Results: Several proteins were differentially expressed in serum of small stable, small progres- sive and large AAA. Three validated proteins (immunoglobulin G (IgG), a1-antitrypsin (a1-AT) and Factor XII activity) showed strong correlation with Dmax. Size combined with either Factor XII activity or a1-antitrypsin had minimal effect on the prognostic value in predicting aneurysm progression compared with size alone (area under the curve (AUC), 0.85; 95% confidence interval (CI), 0.73e0.97; p < 0.001 and AUC, 0.85; 95% CI, 0.72e0.98; p < 0.001 vs. AUC, 0.83; 95% CI, 0.71e0.96; p < 0.001, respectively). Conclusion: The present study indicates that both Factor XII and a1-antitrypsin are found in increased amounts in the serum of patients with expanding AAA. However, combination of either Factor XII or a1-antitrypsin with aneurysm diameter had little effect on prediction of aneurysm progression versus diameter alone.

The role of cardiac troponins (cTn) have become increasingly important in diagnosing myocardial infarction (MI), especially in patients without electrocardiogram abnormalities (1).

Endurance exercise is frequently associated with cardiac troponin (cTn) concentrations, otherwise corresponding to minor myocardial infarction. However, research on the underlying mechanisms has been limited because of assay restraints in the low concentration range.Using the pre-commercial, highly sensitive hs-cTnT assay, cTnT concentrations were measured in samples from recreational runners obtained before and after running 5 km (trained, n = 43/untrained, n = 122), 15 km (n = 38), 21 km (n = 10), and 42 km (n = 85) (all trained). The percentage of runners with elevated cTnT concentrations after the run increased with running distance (0, 11, 13, 40, and 86%), in contrast to NT-proBNP (2, 7, 0, 0, 5). Median (IQR) cTnT post-run concentrations were 0.004 microg/L (0.003), 0.006 microg/L (0.008), 0.010 microg/L (0.006), 0.014 microg/L (0.019), and 0.030 microg/L (0.029), respectively.We found, using a novel hs-cTnT assay, the distance of recreational competitive running to be positively related to asymptomatic increases in cTnT post-run concentrations. In contrast, NT-proBNP showed no increase. In addition, the data indicated that a relatively short running distance of 5 km resulted in cTnT release of untrained participants, in contrast to trained participants, which underlines the necessity of sufficient training. Further effort is needed to clarify the significance of exercise-induced cardiac biomarker elevations.

Objectives This study investigated the relation between abdominal aortic aneurysm (AAA) wall stress, AAA growth rate and biomarker concentrations. With increasing wall stress, more damage may be caused to the AAA wall, possibly leading to progression of the aneurysm and reflection in up- or downregulation of specific circulating biomarkers. Levels of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1, C-reactive protein and alpha 1-antitrypsin were therefore evaluated. Methods Thirty-seven patients (maximum AAA diameter 41–55 mm) with two, three or four consecutive computed tomography angiography (CTA) scans were prospectively included. Diameter growth rate in mm/year was determined between each pair of two sequential CTA scans. AAA wall stress was computed by finite element analysis, based on the first of the two sequential CTA scans only ( n = 69 pairs). Biomarker information was determined in 46 measurements in 18 patients. The relation between AAA diameter and wall stress was determined and the AAA's were divided into three equally sized groups (relative low, medium and high stress). Growth rate and biomarker concentrations were compared between these groups. Additionally, correlation coefficients were computed between absolute wall stress, AAA growth and biomarker concentrations. Results A relative low AAA wall stress was associated with a lower aneurysm growth rate. Growth rate was also positively related to MMP-9 plasma concentration ( r = 0.32). The average MMP-9 and CRP concentrations increased with increasing degrees of relative wall stress, although the absolute and relative wall stress did not correlate with any of the biomarkers. Conclusion Although lower relative wall stress was associated to a lower AAA growth rate, no relation was found between biomarker concentrations and wall stress. Future research may focus on more and extensive biomarker measurements in relation to AAA wall stress.

Defining progression of abdominal aortic aneurysm (AAA) is complicated by several factors, including measurement error, duration of follow-up, and the imaging modality used to assess AAA expansion. Investigations of biomarkers of AAA progression should be standardized so that valid comparisons can be made. Previous research has shown some promising advances towards identifying a reliable and individual predictor of AAA progression. In this second part of our Review on biomarkers of AAA progression, we examine direct and indirect markers of inflammation including various cytokines, C-reactive protein, activators of tissue plasminogen activator and urokinase plasminogen activator, and osteopontin.

Renal impairment is common during and after severe exercise. In clinical practice, renal function is evaluated using serum creatinine, urine parameters, and equations to estimate the Glomular Filtration Rate (GFR). However, creatinine levels may be biased by skeletal muscle damage and the GFR equations, requiring age, gender and body weight, are shown to be inadequate in normals. In the present study, we show that serum cystatin C and creatinine concentrations were elevated after marathon running in 26% and 46% of the 70 recreational male runners, respectively, possibly because of reduction in renal blood flow. The mean cystatin C increase was twice as low as compared to creatinine (21% and 41%, respectively), suggesting that cystatin C is indeed less biased by muscle damage. Future research has to reveal whether training diminishes the elevation in renal markers. Overall, cystatin C seems a more reliable method to establish renal function during and after extensive exercise.

Background: Endurance exercise can increase cardiac troponin (cTn) concentrations as high as those seen in cases of minor myocardial infarction. The inability of most cTn assays to reliably quantify cTn at very low concentrations complicates a thorough data analysis, and the clinical implications of such increases remain unclear. The application of recently developed highly sensitive cTn immunoassays may help resolve these problems. Methods: We evaluated the precommercial highly sensitive cardiac troponin T (hs-cTnT) assay from Roche Diagnostics and the Architect cardiac troponin I (cTnI-Architect) assay from Abbott Diagnostics by testing samples from a reference population of 546 individuals and a cohort of 85 marathon runners. We also measured the samples with the current commercial cTnT assay for comparison. Results: Although the hs-cTnT and cTnI-Architect assays were capable of measuring cTn concentrations at low concentrations ( Conclusions: The hs-cTnT assay was the only assay tested with a performance capability sufficient to detect cTn concentrations in healthy individuals. The number of runners with increased cTn concentrations after a marathon depends highly on an assay’s limit of detection (LOD). The assay with the lowest LOD, the hs-cTnT assay, showed that almost all runners had increased cTn concentrations. The clinical implications of these findings require further investigation.

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individual's risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase-alpha1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin-antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers.

BACKGROUND: Extra-fine hydrofluoroalkane-beclomethasone differs from other inhaled corticosteroids by its fine aerosol characteristics. Therefore, extra-fine hydrofluoroalkane-beclomethasone may be particularly useful for treating peripheral airway inflammation in asthma. OBJECTIVE: To analyze the anti-inflammatory effects of extra-fine hydrofluoroalkane-beclomethasone vs fluticasone dry powder inhaler (DPI) in asthmatic children by measuring bronchial and alveolar nitric oxide (NO) and inflammatory markers in exhaled breath condensate (EBC). METHODS: In a 6-month crossover study, 33 children aged 6 to 12 years with moderate persistent asthma were randomly treated with extra-fine hydrofluoroalkane-beclomethasone (200 microg daily via an Autohaler) and fluticasone DPI (200 microg daily via a Diskus). The primary outcome variables were alveolar NO concentration and bronchial NO flux. The secondary outcome variables were levels of inflammatory markers in EBC, lung function indices, symptoms, exacerbations, and adverse effects. All the variables were recorded at baseline and after each treatment period. RESULTS: Mean +/- SE alveolar NO concentration and bronchial NO flux were comparable after treatment with hydrofluoroalkane-beclomethasone vs fluticasone DPI (4.7 +/- 0.5 vs 4.3 +/- 0.5 ppb, P = .55, and 1,124.3 +/- 253.6 vs 1,029.1 +/- 195.5 pL/s, P = .70, respectively). In addition, levels of inflammatory markers in EBC, lung function indices, and symptoms did not differ between treatments. Patients used fewer beta2-agonists during the last 2 weeks of hydrofluoroalkane-beclomethasone treatment. CONCLUSION: The anti-inflammatory effects of hydrofluoroalkane-beclomethasone are similar to those of fluticasone DPI in children with moderate persistent asthma.

Optimal collection and analysis of exhaled breath condensate (EBC) are prerequisites for standardisation and reproducibility of assessments. The present study aimed to assess reproducibility of EBC volume, hydrogen peroxide (H(2)O(2)), 8-isoprostane and cytokine measurements using different condensers, including a newly developed glass condenser. At four points in time, 30 healthy subjects performed sequential EBC collections randomly using the following four condensers: glass, silicone, EcoScreen (Erich Jaeger GmbH, Hoechberg, Germany) and an optimised glass condenser. In small EBC samples, H(2)O(2) was measured by spectrophotometer, 8-isoprostane by enzyme immunoassay, and cytokines by multiplexed xMAP technology (Luminex Corporation, Austin, TX, USA). The optimised glass condenser yielded significantly more EBC volume (median 2,025 microL, interquartile range 1,600-2,525). The reproducibility of EBC volume, yielded by the new glass condenser, was comparable with EcoScreen (19-20 coefficients of variation (CV)%), but was significantly better compared with silicone and glass (29-37 CV%). The new condenser was associated with significantly more detections of H(2)O(2), 8-isoprostane, interleukin-2, -4, -5 and -13, and tumour necrosis factor-alpha. Isoprostane concentrations were significantly higher using the new condenser, whereas H(2)O(2) and cytokine concentrations were not. Reproducibility of biomarkers was equally variable for all condenser types. In conclusion, significantly more exhaled breath condensate volume and biomarker detections were found using the optimised glass condenser, including higher 8-isoprostane levels. However, biomarker reproducibility in exhaled breath condensate in healthy adults was not influenced by the type of condenser.

Aim: Ankylosing spondylitis (AS) is a chronic systemic inflammatory rheumatic disorder that primarily affects the axial skeleton. To date there is no satisfactory biomarker for diagnosis or prognosis of AS. This study is focused on detection of potential biomarkers for the diagnosis of AS using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with the ultimate goal of developing a progression biomarker for AS. Materials & methods: Protein profiles of sera of 38 AS patients and 38 healthy controls were obtained using ProteinChip arrays. Different arrays and conditions were compared with find out which condition resulted in the optimal discrimination of both groups. Results: Optimal discrimination was reached using weak cation exchange (CM10) and immobilized metal affinity capture coupled with copper (IMAC-Cu2+) arrays. Using a multimarker approach on protein profiles obtained with CM10 arrays resulted in a sensitivity of 66% and a specificity of 74%. Using a multimarker approach on protein profiles obtained with IMAC-Cu2+ arrays resulted in a sensitivity and specificity of 70%. Conclusions: This is the first study that shows that protein profiling in serum using SELDI-TOF-MS can be used as a diagnostic tool for AS. The biomarkers will be validated to confirm if they can be used as progression biomarkers.

BACKGROUND: Exhaled nitric oxide and inflammatory biomarkers in exhaled breath condensate may be useful to diagnose and monitor childhood asthma. Their ability to indicate an asthma diagnosis, and to assess asthma severity and control, is largely unknown. OBJECTIVE: To study (1) the ability of exhaled nitric oxide and inflammatory markers in exhaled breath condensate (nitrite, nitrate, hydrogen peroxide, 8-isoprostane, IFN-gamma, TNF-alpha, IL-2, -4, -5, -10 and acidity) to discriminate between childhood asthma and controls. (2) The ability of these biomarkers to indicate asthma severity and control. METHODS: One-hundred and fourteen children were included: 64 asthmatics (10.7+/-3.0 years, 67.2% atopic) and 50 controls (10.0+/-0.4 years). Condensate was collected using a glass condenser. RESULTS: Exhaled nitric oxide, IFN-gamma and IL-4 in exhaled breath condensate differed significantly between asthma and controls. Multivariate backward logistic regression models demonstrated that IL-4 (odds ratio 7.9, 95% confidence interval 1.2-51.0) was the only significant indicator of an asthma diagnosis. Asthma control was best assessed by exhaled nitric oxide, 8-isoprostane, IFN-gamma and IL-4 (sensitivity 82%, specificity 80%, P

Objectives: Cardiac troponin T (cTnT) degradation after tissue release is still under debate. Because degradation of cTnT might have consequences on clearance of the molecule from the circulation, but also on the assay performance, the aim of this study was to investigate cTnT release and degradation in serum of AMI patients. Design and methods: Serum samples were collected from 20 patients with AMI diagnosis undergoing rapid revascularization. Intact cTnT and fragments were detected using a combination of immunoprecipitation, SDS-PAGE and Western blotting. Results: The intact cTnT protein was detected only during the first 12 h after the cTnT concentration started to increase above the AMI cut-off value of 0.03 μg/L. Thereafter only fragments with molecular weights ranging from 10 to 30 kDa were detected, with two fragments being most prominent (15 and 25 kDa). Conclusions: Intact cTnT rapidly disappears from the circulation during the early hours after AMI, but immunoreactive fragments remain present longer. The current cTnT immunoassay detects both intact cTnT and fragments.

BACKGROUND: Sarcoidosis is a multi-systemic inflammatory disorder, which affects the lungs in 90% of the cases. The main pathologic feature is chronic inflammation resulting in non-caseating granuloma formation. Until now there is no satisfying biomarker for diagnosis or prognosis of sarcoidosis. This study is focused on the detection of potential biomarkers in serum for the diagnosis of sarcoidosis using surface-enhanced laser desorption ionization-time of flight-mass spectrometry (SELDI-TOF-MS). METHODS: For detection of potential biomarkers, protein profiles of anion exchange fractionated serum of 35 sarcoidosis patients and 35 healthy controls were compared using SELDI-TOF-MS. Sensitivities and specificities of the potential biomarkers obtained with SELDI-TOF-MS, generated with decision tree algorithm, were compared to the conventional markers angiotensin converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R). RESULTS: Optimal classification was achieved with metal affinity binding arrays. A single marker with a mass-to-charge (m/z) value of 11,955 resulted in a sensitivity and specificity of 86% and 63%, respectively. A multimarker approach of two peaks, m/z values of 11,734 and 17,377, resulted in a sensitivity and specificity of 74% and 71%, respectively. These sensitivities and specificities were higher compared to measurements of ACE and sIL-2R. Identification of the peak at m/z 17,377 resulted in the alpha-2chain of haptoglobin. CONCLUSIONS: This study acts as a proof-of-principle for the use of SELDI-TOF-MS in the detection of new biomarkers for sarcoidosis. The peak of the multimarker at m/z 17,377 was identified as the alpha-2chain of haptoglobin.

The diagnosis of acute myocardial infraction has undergone a noticeable transformation sincethe introduction of the high-sensitivity cardiac troponin assays. The clear shift towards increasingly rapidclinical decision making is reflected in the most recent European Society of Cardiology guidelines, whichinclude a 0-/1-hour algorithm for the diagnosis of non-ST-elevation myocardial infarction. The use of thisalgorithm enables rule-in or rule-out in approximately 70–75% of all patients after a second cardiac troponinmeasurement after one hour. In a minority of patients rule-in or rule-out is achievable even faster; after onlya single blood draw at presentation. Since rapid clinical decision making has several advantages, like fastinitiation of treatment for those who need it and preventing prolonged patient anxiety, various recent studieshave tried to further optimize these cut-off values at presentation.

Background Continuous dialysis could provide benefit by constant removal of potassium and phosphate. This study investigates the suitability of specific potassium and phosphate sorbents for incorporation in an extracorporeal device by capacity and regenerability testing. Methods Capacity testing was performed in uraemic plasma. Regenerability was tested for potassium sorbents, with adsorption based on cationic exchange for sodium, with 0.1 M and 1.0 M NaCl. To regenerate phosphate sorbents, with adsorption based on anionic exchange, 0.1 M and 1.0 M NaHCO3 and NaOH were used. Subsequently, sodium polystyrene divinylbenzene sulphonate (RES-A) and iron oxide hydroxide (FeOOH) beads were incorporated in a cartridge for testing in bovine blood using a recirculating blood circuit and a dialysis circuit separated by a high-flux dialyzer (dynamic setup). Preloading was tested to assess whether this could limit calcium and magnesium adsorption. Results In the batch-binding assays, zirconium phosphate most potently adsorbed potassium (0.44 ± 0.05 mmol/g) and RES-A was the best regenerable potassium sorbent (92.9 ± 5.7% with 0.1 M NaCl). Zirconium oxide hydroxide (ZIR-hydr) most potently adsorbed phosphate (0.23 ± 0.05 mmol/g) and the polymeric amine sevelamer carbonate was the best regenerable sorbent (85.7 ± 5.2% with 0.1 M NaHCO3). In the dynamic setup, a potassium adsorption of 10.72 ± 2.06 mmol in 3 h was achieved using 111 g of RES-A and a phosphate adsorption of 4.73 ± 0.53 mmol in 3 h using 55 g of FeOOH. Calcium and magnesium preloading was shown to reduce the net adsorption in 3 h from 3.57 ± 0.91 to -0.29 ± 1.85 and 1.02 ± 0.05 to -0.31 ± 0.18 mmol, respectively. Conclusion RES-A and FeOOH are suitable, regenerizable sorbents for potassium and phosphate removal in dialysate regeneration. Use of zirconium carbonate and ZIR-hydr may further increase phosphate adsorption, but may compromise sorbent regenerability. Use of polymeric amines for phosphate adsorption may enhance sorbent regenerability. Calcium and magnesium preloading considerably reduced net adsorption of these ions.

LEENDERS, M., L. B. VERDIJK, L. VAN DER HOEVEN, J. VAN KRANENBURG, R. NILWIK, W. K. W. H. WODZIG, J. M. G. SENDEN, H. A. KEIZER, and L. J. C. VAN LOON. Protien Supplementation during Resistance-Type Exercise Training in the Elderly. Med. Sci. Sports Exerc., Vol. 45, No. 3, pp. 542–552, 2013. Introduction: Resistance training has been well established as an effective treatment strategy to increase skeletal muscle mass and strength in the elderly. We assessed whether dietary protein supplementation can further augment the adaptive response to prolonged resistance-type exercise training in healthy elderly men and women. Methods: Healthy elderly men (n = 31, 70 T 1 yr) and women (n = 29, 70 T 1 yr) were randomly assigned to a progressive, 24-wk resistance-type exercise training program with or without additional protein supplementation (15 gIdj1 ). Muscle hypertrophy was assessed on a wholebody Dual-energy X-ray absorptiometry (DXA), limb (computed tomography), and muscle fiber (biopsy) level. Strength was assessed regularly by 1-repetition maximum (RM) strength testing. Functional capacity was assessed with a sit-to-stand and handgrip test. Results: One-RM strength increased by 45% T 6% versus 40% T 3% (women) and 41% T 4% versus 44% T 3% (men) in the placebo versus protein group, respectively (P G 0.001), with no differences between groups. Leg muscle mass (women, 4% T 1% vs 3% T 1%; men, 3% T 1% vs 3% T 1%) and quadriceps cross-sectional area (women, 9% T 1% vs 9% T 1%; men, 9% T 1% vs 10% T 1%) increased similarly in the placebo versus protein groups (P G 0.001). Type II muscle fiber size increased over time in both placebo and protein groups (25% T 13% vs 30% T 9% and 23% T 12% vs 22% T 10% in the women and men, respectively). Sit-to-stand improved by 18% T 2% and 19% T 2% in women and men, respectively (P G 0.001). Conclusion: Prolonged resistance-type exercise training increases skeletal muscle mass and strength, augments functional capacity, improves glycemia and lipidemia, and reduces blood pressure in healthy elderly men and women. Additional protein supplementation (15 gIdj1 ) does not further increase muscle mass, strength, and/or functional capacity

Item does not contain fulltext BACKGROUND: Underdiagnosis and low levels of asthma control are frequent occurring problems in patients with asthma. OBJECTIVE: The study aim was to evaluate the ability of non-invasive inflammatory markers in exhaled breath to predict exacerbations of childhood asthma, and to assess the time course of changes in these exhaled markers before, during and after exacerbations. METHODS: The design was a prospective one-year longitudinal study. Regular two-month visits at the outpatient clinic were performed. Forty children with asthma (aged 6-16 years) participated. The primary outcome measure was the occurrence of an exacerbation. Assessment was made of the presence and severity of pulmonary symptoms, use of medication, and measurements of forced expiratory volume in 1 s using home monitor. The following independent parameters were assessed during outpatient visits: (1) exhaled nitric oxide, (2) inflammatory markers in exhaled breath condensate: acidity, nitrite, hydrogen peroxide, interleukin-1alpha, -5, -13, interferon-gamma, (3) lung function, (4) asthma control score. RESULTS: Thirty-eight of 40 children completed the study. Sixteen children developed exacerbations, of which ten were moderate and six severe. Univariate Cox regression analysis revealed that condensate acidity, interleukin-5 and asthma control score were significant predictors of an asthma exacerbation (P < 0.05). In the multivariate Cox regression analysis, exacerbations were best predicted by the asthma control score and by the level of interleukin-5 in exhaled breath condensate (Wald scores of 7.19 and 4.44, P = 0.007 and P = 0.035 respectively). The predicted survival curve of this multivariate model showed a two times reduced risk on exacerbations in the category of children with the 10% most optimal values of IL-5 and asthma control score. CONCLUSIONS AND CLINICAL RELEVANCE: Both exhaled breath condensate interleukin-5 level and asthma control score were significant predictors of asthma exacerbations. These findings open up the possibility of assessing the potential of such parameters to titrate asthma treatment in future studies.

Contains fulltext : 88162.pdf ( ) (Closed access) Individuals with a spinal cord injury (SCI) have an increased cardiovascular risk. We hypothesize that (anti)oxidative imbalance is associated with the increased cardiovascular risk in SCI, while exercise can reverse this status. The aim of the study is to compare baseline levels of oxidative stress and antioxidative capacity between individuals with SCI and able-bodied (AB) subjects, and to assess acute and long-term effects of functional electrical stimulation (FES) exercise on oxidative stress and antioxidative capacity in SCI. Venous blood was taken from subjects with an SCI (n = 9) and age- and gender-matched AB subjects (n = 9) to examine oxidative stress through malondialdehyde (MDA) levels, while superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme levels represented anti-oxidative capacity. Subsequently, subjects with an SCI performed an 8-week FES exercise training period. Blood was taken before and after the first exercise bout and after the last FES session to examine the acute and chronic effect of FES exercise, respectively. Baseline levels of MDA, SOD and GPx were not different between individuals with SCI and AB subjects. SCI demonstrated a correlation between initial fitness level and MDA (R = -0.83, P = 0.05). MDA, SOD and GPx levels were neither altered by a single FES exercise bout nor by 8 weeks FES training. In conclusion, although individuals with an SCI demonstrate a preserved (anti)oxidative status, the correlation between fitness level and (anti)oxidative balance suggests that higher fitness levels are related to improved (anti)oxidative status in SCI. Nonetheless, the FES exercise stimulus was insufficient to acutely or chronically change (anti)oxidative status in individuals with an SCI. 01 augustus 2010

BACKGROUND: Inflammation, overhydration and elevated cardiac biomarkers are related to outcome in haemodialysis (HD) patients. Here, we explored the relationship between the body composition (BC), inflammation and cardiac biomarker concentrations in HD patients longitudinally. METHODS: A total of 44 HD patients were followed for 6 months. BC was assessed by multifrequency bioimpedance (BIA). Serum concentrations of cardiac troponin T (cTnT), high-sensitive C-reactive protein (hsCRP), brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) were assessed at 2 monthly intervals. The longitudinal data analysis was conducted with a marginal model. RESULTS: During the follow-up, the parameters describing the BC were highly predictive of both BNP and NT-proBNP and independent of gender, time, hsCRP and cTnT concentrations. The intracellular water (ICW)/body weight (BW) ratio (reflecting malnutrition) exerted a negative effect, whereas the extracellular water (ECW)/BW ratio (reflecting overhydration) had a positive effect on BNP and NT-proBNP concentrations. HsCRP and cTnT concentrations were significantly associated with each other. Furthermore, NT-proBNP concentrations were predictive of cTnT and hsCRP concentrations. CONCLUSIONS: In the present study, we find a significant relation between BIA-derived BC parameters and natriuretic peptide concentrations. This relationship was independent of the cardiac history of the patient and suggests that the natriuretic peptide levels are to some degree modifiable by changing a patient's fluid distribution. Moreover, cTnT, BNP, NT-proBNP and hsCRP were significantly related, showing a complex relation between overhydration, malnutrition, inflammation and cardiac biomarkers in dialysis patients.

Background Elevated cardiac troponin (cTn) concentrations predict an increased mortality in patients suffering from end-stage renal disease (ESRD). This study compares the performance of a precommercial high-sensitive cTnT assay (hs-cTnT) with two contemporary cTn assays in detecting cTn elevations in ESRD patients during a six-month follow-up. Methods Thirty-two ESRD patients were followed for six months, during which cTn concentrations were assessed every two months. Baseline biomarker concentrations were compared with those in a simultaneously measured reference population of 501 healthy subjects. Results During follow-up 26 (81%), 32 (100%) and 9 (28%) of the patients showed elevated cTn concentrations according to the current cTnT, the hs-cTnT and the cTnI assays, respectively. The range of concentrations measured in each patient had a median (interquartile range) magnitude of 0.03 μg/L (0.02–0.06), 0.017 μg/L (0.011–0.029) and 0.011 μg/L (0–0.017) according to the aforementioned assays. Conclusion According to the hs-cTnT assay, all of the ESRD patients had elevated cTnT concentrations at least once during the follow-up. As elevated cTn concentrations are highly prognostic of adverse events, the use of serial measurements has thus identified additional patients at risk for such events. The fact that we find cTn concentrations to be higher in patients with a history of cardiac disease is in line with this. Additional studies in ESRD patients are needed to investigate the added diagnostic and prognostic value of the very low cTnT concentrations and variations detected only by the hs-cTnT assay.

BACKGROUND: Considerable discrepancy exists in the literature on the proposed benefits of protein supplementation on the adaptive response of skeletal muscle to resistance-type exercise training in the elderly. OBJECTIVE: The objective was to assess the benefits of timed protein supplementation on the increase in muscle mass and strength during prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. DESIGN: Healthy elderly men (n = 26) aged 72 +/- 2 y were randomly assigned to a progressive, 12-wk resistance-type exercise training program with (protein group) or without (placebo group) protein provided before and immediately after each exercise session (3 sessions/wk, 20 g protein/session). One-repetition maximum (1RM) tests were performed regularly to ensure a progressive workload during the intervention. Muscle hypertrophy was assessed at the whole-body (dual-energy X-ray absorptiometry), limb (computed tomography), and muscle fiber (biopsy) level. RESULTS: The 1RM strength increased approximately 25-35% in both groups (P < 0.001). Dual-energy X-ray absorptiometry and computed tomography scans showed similar increases in leg muscle mass (6 +/- 1% in both groups; P < 0.001) and in the quadriceps (9 +/- 1% in both groups), from 75.9 +/- 3.7 and 73.8 +/- 3.2 to 82.4 +/- 3.9 and 80.0 +/- 3.0 cm2 in the placebo and protein groups, respectively (P < 0.001). Muscle fiber hypertrophy was greater in type II (placebo: 28 +/- 6%; protein: 29 +/- 4%) than in type I (placebo: 5 +/- 4%; protein: 13 +/- 6%) fibers, but the difference between groups was not significant. CONCLUSION: Timed protein supplementation immediately before and after exercise does not further augment the increase in skeletal muscle mass and strength after prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. This trial was registered at clinicaltrials.gov as NCT00744094.

Over the past 2 decades, there has been a large interest in cardiac troponin T (cTnT) elevations, which are often seen following endurance sport events. There have been many reports on this topic, although sometimes with different approaches. We reviewed the available literature on cTnT elevations after prolonged strenuous exercise and discovered profound differences in the percentage of subjects reported to have elevated cTnT concentrations. This could partly be attributed to differences in immunoassay characteristics, such as cross-reactivity with skeletal troponin T, and the use of different cut-off values used in the different studies. The elevations were transient, with levels decreasing to pre-event concentrations within 24-48 hours. This might be explained by the relatively short half-life of cTnT, or water imbalance during and after the event. The release mechanism of cTnT, as well as the long-term positive or negative effects, remains unclear. Future research should therefore be aimed at clarifying the release mechanism of cTnT. Furthermore, the benefits and the possible long-term negative aspects of prolonged exercise should be evaluated.

There is a need for better markers for the diagnosis and prognosis of chronic inflammatory diseases. Proteomic strategies can be helpful to detect new biomarkers. Proteomic analyses are performed to characterize the behaviour of the system rather than the behaviour of any single component. Since the genome has been unravelled, the proteome received more attention. Aim of this review was to focus on the use of different proteomics techniques to detect potential and/or common biomarkers in chronic inflammatory diseases. The identified and validated proteins detected in the different studies are compared and discussed to conclude if there are some common markers which can be used in the diagnosis and prognosis of the three chronic inflammatory diseases described in this study; multiple sclerosis, rheumatic diseases and lung inflammatory diseases. The heat shock protein family (hsp) was entitled as biomarkers with potential for further research in multiple sclerosis. Myeloid-related protein 8 (MRP-8) was found in three different rheumatoid arthritis (RA) studies with different sample materials and could be a potential marker for RA. α1-Antitrypsin was validated in two studies as a marker for sarcoidosis and α1-antitrypsin was also found to be a marker for cystic fibrosis (CF), together with myeloperoxidase and IgG.

Summary Background The value of elevated serum angiotensin-converting enzyme (ACE) activity in the diagnosis and follow-up in sarcoidosis is a matter of ongoing debate. This may be at least related to the insertion (I)/deletion (D) polymorphism in the ACE gene (ACE I/D). ACE activity is influenced by the ACE I/D polymorphism. As a consequence, the use of one reference interval instead of three genotype-specific reference intervals for ACE activity may lead to a less precise interpretation of ACE activity. Methods In order to assess whether determination of ACE activity indeed requires the ACE I/D genotype to be taken into account, we established ACE I/D-corrected reference intervals in healthy, Caucasian volunteers ( n =200). In addition, ACE activities in ACE I/D genotyped patients suspected of or having sarcoidosis ( n =129) were expressed as the Z -score related to ACE I/D-corrected reference intervals. Results Comparison of the Z -score with ACE activity in which ACE I/D is ignored rendered 8.5% misclassification of ‘elevated' versus ‘normal' ACE or vice versa. Conclusions Our data demonstrate a convenient way to circumvent the use of three reference intervals by introducing a Z -score for ACE activity. It also illustrates the need to re-investigating the possible clinical value of serum ACE activity in sarcoidosis by considering ACE I/D.

In vitro and in vivo animal studies have reported strong insulin-like or insulin-potentiating effects after cinnamon administration. Recently, a human intervention study showed that cinnamon supplementation (1 g/d) strongly reduced fasting blood glucose concentration (30%) and improved the blood lipid profile in patients with type 2 diabetes. The objective of this study was to investigate the effects of cinnamon supplementation on insulin sensitivity and/or glucose tolerance and blood lipid profile in patients with type 2 diabetes. Therefore, a total of 25 postmenopausal patients with type 2 diabetes (aged 62.9 +/- 1.5 y, BMI 30.4 +/- 0.9 kg/m(2)) participated in a 6-wk intervention during which they were supplemented with either cinnamon (Cinnamomum cassia, 1.5 g/d) or a placebo. Before and after 2 and 6 wk of supplementation, arterialized blood samples were obtained and oral glucose tolerance tests were performed. Blood lipid profiles and multiple indices of whole-body insulin sensitivity were determined. There were no time x treatment interactions for whole-body insulin sensitivity or oral glucose tolerance. The blood lipid profile of fasting subjects did not change after cinnamon supplementation. We conclude that cinnamon supplementation (1.5 g/d) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid profile in postmenopausal patients with type 2 diabetes. More research on the proposed health benefits of cinnamon supplementation is warranted before health claims should be made. AD - Department of Clinical Chemistry, Academic Hospital Maastricht, The Netherlands.

Objectives: Electrical remodeling in cardiac hypertrophy often involves the downregulation of K+ currents, including beta-adrenergic (beta-A)-sensitive I-Ks. Temporal patterns of ion-channel downregulation are poorly resolved. In dogs with complete atrioventricular block (AVB), we examined (1) the time course of molecular alterations underlying I-Ks downregulation from acute to chronic hypertrophy; and (2) concomitant changing responses of repolarization to beta-adrenergic receptor (beta-AR) stimulation. Methods and Results: Serial left-ventricular (LV) biopsies were collected from anesthetized dogs during sinus rhythm (SR; control) and at 3, 7 and 30 days of AVB. KCNQ1 mRNA and protein decreased within 3 days (protein expression 58 +/- 10% of control), remaining low thereafter. beta 1-AR mRNA and protein decreased more gradually to 53 +/- 8% at 7 days. In chronic-AVB LV myocytes, I-Ks-tail density was reduced: 1.4 +/- 0.3 pA/pF versus 2.6 +/- 0.4 pA/pF in controls. beta-A enhancement of I-Ks was reduced. Isoproterenol shortened action-potential duration in control cells, while causing heterogeneous repolarization responses in chronic AVB. beta-A early afterdepolarizations were induced in 4 of 13 chronic-AVB cells, but not in controls. In intact conscious dogs, isoproterenol shortened QT(c) at SR (by -8 +/- 3% from 295 ms), left it unaltered at 3 days AVB (+1 +/- 3% from 325 ms) and prolonged QT(c) at 30 days (+6 +/- 3% from 365 ms). Conclusions: Profound decrease of KCNQ1 occurs within days after AVB induction and is followed by a more gradual decrease of beta 1-AR expression. Downregulation and blunted beta-A activation of I-Ks contribute to the loss of beta-A-induced shortening of ventricular repolarization, favoring proarrhythmia. Provocation testing with isoproterenol identifies repolarization instability based on acquired channelopathy.

OBJECTIVE: The aim of the study was evaluating the diagnostic value of plasma matrix metalloproteinase- (MMP)-2 and -9 and tissue inhibitor of MMP-1 (TIMP-1) for endoleak detection after endovascular aneurysm repair (EVAR). REPORT: Consecutive EVAR patients (n = 17) with endoleak and matched controls without endoleak (n = 20) were prospectively enrolled. Increased levels of MMP-9 were observed in patients with endoleak (P < 0.001). Regression analysis showed no significant influence of age, sex or abdominal aortic aneurysm (AAA) size. The receiver operating characteristic (ROC) curve of plasma MMP-9 levels showed that a cut-off value of 55.18 ng ml(-1) resulted in 100% sensitivity and 96% specificity with an AUC value of 0.988 (P < 0.001) to detect endoleak. CONCLUSIONS: Plasma MMP-9 levels appear to discriminate between patients with and without an endoleak with high sensitivity and specificity.

BACKGROUND: Weight regain after weight loss is common. In the Diogenes dietary intervention study, high protein and low glycemic index (GI) diet improved weight maintenance. OBJECTIVE: To identify blood predictors for weight change after weight loss following the dietary intervention within the Diogenes study. DESIGN: Blood samples were collected at baseline and after 8-week low caloric diet-induced weight loss from 48 women who continued to lose weight and 48 women who regained weight during subsequent 6-month dietary intervention period with 4 diets varying in protein and GI levels. Thirty-one proteins and 3 steroid hormones were measured. RESULTS: Angiotensin I converting enzyme (ACE) was the most important predictor. Its greater reduction during the 8-week weight loss was related to continued weight loss during the subsequent 6 months, identified by both Logistic Regression and Random Forests analyses. The prediction power of ACE was influenced by immunoproteins, particularly fibrinogen. Leptin, luteinizing hormone and some immunoproteins showed interactions with dietary protein level, while interleukin 8 showed interaction with GI level on the prediction of weight maintenance. A predictor panel of 15 variables enabled an optimal classification by Random Forests with an error rate of 24+/-1%. A logistic regression model with independent variables from 9 blood analytes had a prediction accuracy of 92%. CONCLUSIONS: A selected panel of blood proteins/steroids can predict the weight change after weight loss. ACE may play an important role in weight maintenance. The interactions of blood factors with dietary components are important for personalized dietary advice after weight loss. REGISTRATION: ClinicalTrials.gov NCT00390637.

Contains fulltext : 70193.pdf (Publisher’s version ) (Closed access) Chronic airway inflammation is present in cystic fibrosis (CF). Non-invasive inflammometry may be useful in disease management. The aim of the present cross-sectional study was to investigate: (i) the ability of fractional exhaled nitric oxide and inflammatory markers (IM) [exhaled breath condensate (EBC) acidity, nitrite, nitrate, hydrogen peroxide (H(2)O(2)), 8-isoprostane, Th1/Th2 cytokines] to indicate (exacerbations of) CF; and (ii) the ability of these non-invasive IM to indicate CF disease severity. In 98 children (48 CF/50 controls), exhaled nitric oxide was measured using the NIOX, and condensate was collected using a glass condenser. In CF interferon (IFN-gamma) and nitrite concentrations were significantly higher, whereas exhaled nitric oxide levels were significantly lower compared with controls (3.3 +/- 0.3 pg/ml, 2.2 +/- 0.2 microM, 10.0 +/- 1.2 p.p.b. vs. 2.6 +/- 0.2 pg/ml, 1.4 +/- 0.1 microM, 15.4 +/- 1.4 p.p.b. respectively). Using multivariate logistic regression models, the presence of CF was best indicated by 8-isoprostane, nitrite and IFN-gamma [sensitivity 78%, specificity 83%; area under receiver operating characteristic curve (AUC) 0.906, p < 0.001]. An exacerbation of CF was best indicated by 8-isoprostane and nitrite (sensitivity 40%, specificity 97%, AUC curve 0.838, p = 0.009). Most indicative biomarkers of CF severity were exhaled nitric oxide, and condensate acidity (sensitivity 96%, specificity 67%; AUC curve 0.751, p = 0.008). In this cross-sectional study, the combination of different exhaled IM could indicate (exacerbations of) CF, and severity of the disease in children. Longitudinal data are necessary to further confirm the role of these markers for the management of CF in children.