Medical do students in the Netherlands have the opportunity to follow an internship abroad. However, this is often at the expense of obliged developing their competence, for example in situations where they do not learn abroad what they would have learnt had they had followed the Dutch programme. An international internship should, therefore, not be obliged for all medical students.

BACKGROUND:to The aim of this study was to disentangle the contribution of muscular vs pulmonary oxidative stress during endurance exercise in leg patients with COPD. METHODS: Fifteen COPD patients and 10 healthy age-matched controls performed a continuously submaximal single leg ergometer test COPD (40% of peak workload) for 20 min or until they stopped (Tlim). Venous blood, urine samples and exhaled breath condensate COPD were sampled before, immediately and 2h after exercise. RESULTS: Tlim was lower in COPD than controls (p < .01). No patients exercise-induced systemic inflammation (IL-6, TNF-alpha) was found in the groups. Urinary malondialdehyde (MDA) and uric acid (p < .05) were not increased in COPD whereas erythrocyte GSSG/GSH tended to be increased in COPD compared to controls after exercise (p = .08).controls Despite the relatively low cardioventilatory response to this localized muscle exercise, hydrogen peroxide (H(2)O(2)) in breath condensate significantly increased in pulmonary COPD (p < .01). NF-kappaB DNA binding activity of p50 in peripheral blood monocytes was elevated after exercise in both peripheral COPD (p < .01) and controls (p < .05), whereas p65 protein was not altered. CONCLUSION: COPD patients showed increased Despite pulmonary and systemic oxidative stress after localized leg muscle exercise compared to healthy controls without evidence of increased levels of exercise systemic inflammation.

Ferulic the acid (FA) is the most abundant phenolic compound in wheat grain, mainly located in the bran. However, its bioaccessibility from phenolic the bran matrix is extremely low. Different bioprocessing techniques involving fermentation or enzymatic and fermentation treatments of wheat bran were treatment developed aiming at improving the bioaccessibility of phenolic compounds in bran-containing breads. The bioaccessibility of ferulic acid, p-coumaric acid, and 3-phenylpropionic sinapic acid was assessed with an in vitro model of upper gastrointestinal tract (TIM-1). Colonic metabolism of the phenolic compounds acid. in the nonbioaccessible fraction of the breads was studied with an in vitro model of human colon (TIM-2). The most acid effective treatment was the combination of enzymes and fermentation that increased the bioaccessibility of FA from 1.1% to 5.5%. The The major colonic metabolites were 3-(3-hydroxyphenyl)propionic acid and 3-phenylpropionic acid. Bran bioprocessing increases the bioaccessibility of phenolic compounds as well as wheat the colonic end metabolite 3-phenylpropionic acid.

Activation ERK1/2 of the NADPH oxidase homolog dual oxidase 1 (DUOX1) within the airway epithelium cells represents a key mechanism of innate H2O2-dependent airway host defense, through enhanced production of H2O2 mediating cellular signaling pathways that regulate the production of various inflammatory mediators.were Production of the CXC chemokine interleukin (IL)-8/CXCL8 forms a common epithelial response to many diverse stimuli, including bacterial and viral DUOX1 triggers, environmental oxidants, and other biological mediators, suggesting the potential involvement of a common signaling pathway that may involve DUOX1-dependent activation H2O2 production. Following previous reports showing that DUOX1 is activated by extracellular ATP and purinergic receptor stimulation, the present studies results demonstrate that airway epithelial IL-8 production in response to several bacterial stimuli involves ATP release and DUOX1 activation. ATP-mediated DUOX1 which activation resulted in the activation of ERK1/2 and NF-B pathways, which was associated with epidermal growth factor (EGFR) ligand shedding key by ADAM17 (a disintegrin and metalloproteinase-17). Although ATP-mediated ADAM17 activation and IL-8 release were not prevented by extracellular H2O2 scavenging redox by catalase, these responses were attenuated by intracellular scavengers of H2O2 or related oxidants, suggesting an intracellular redox signaling mechanism.ADAM17 Both ADAM17 activation and IL-8 release were suppressed by inhibitors of EGFR/ERK1/2 signaling, which can regulate ADAM17 activity by serine/threonine factor phosphorylation. Collectively, our results indicate that ATP-mediated DUOX1 activation represents a common response mechanism to several environmental stimuli, involving H2O2-dependent and EGFR/ERK activation, ADAM17 activation and EGFR ligand shedding, leading to amplified epithelial EGFR activation and IL-8 production.

Some treatment patients with sarcoidosis can have cardiac involvement. Impairment of the cardiac sympathetic nerve activity is seen in about 50% of stress, the sarcoidosis patients with small fiber neuropathy. In this case we present a sarcoidosis patient with small fiber neuropathy and improvement cardiac symptoms with a cardiac sympathetic dysfunction, assessed with I-123 MIBG SPECT. After 5 months of treatment with carvedilol, which relevance has besides adrenergic receptor blocking effects also antioxidant action, we saw a clear improvement of the cardiac sympathetic function demonstrated of on a repeated I-123 MIBG SPECT. Future studies should explore the clinical relevance of the relation of oxidative stress, antioxidant the therapy and cardiac dysfunction in sarcoidosis.

The the activity of antioxidants is frequently determined in competition assays. In these assays an antioxidant (A) and detector molecule (D) compete to for the reactive species (R). The competitive inhibitory effect of A on the reaction of D with R is a differences measure of the antioxidant activity of A. In determining the activity of A, it is in general incorrectly assumed that of the concentrations of A and D remain equal to the initial concentration. However, the principle of the assay is that of some A and D is consumed assay and consequently the concentration of A and D will decrease during a competition assay, assay, resulting in a deviation in the observed antioxidant activity. Computer modeling was used to obtain a graphical tool to competition estimate the extent of the deviation caused by the incorrect assumption that the concentrations of A and D do not detector decrease. Several competition assays are evaluated using this graphical tool, demonstrating that frequently inaccurate antioxidant activities have been reported. In towards general, differences between antioxidants are underestimated and the activity of all antioxidants shifts towards the antioxidant activity of D. A do strategy is provided to improve the accuracy of a competition assay. To obtain accurate results in a competition assay, the concentrations reaction rate constant of the detector molecule with the reactive species should be comparable to that of the antioxidant. In of addition, the concentration of reactive species should be as low as possible.

Recently,(IL)-6, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo. PARP-1 is from recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such < as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). In this study, we assessed the antiinflammatory effects of PARP-1-inhibiting flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men. A total flavonoids of 10 COPD, 10 T2D patients, and 10 healthy volunteers matched for age and BMI were recruited. Blood from each by participant was exposed to 1 microg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 micromol/L of flavone,concentrations fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6,-8, and -10 were measured in the supernatant.vivo. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/-and SEM):-41 +/- 4%(fisetin) and -31 +/- 4%(tricetin); P < .001] and IL-6 in blood from T2D patients attenuated [-31 +/- 5%(fisetin) and -29 +/- 6%(tricetin); P < or = .001]. Moreover, LPS-induced changes in TNFalpha and with IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin. The PARP-1-inhibiting flavonoids fisetin and tricetin Blood were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as Blood nutraceutical agents for these patient groups.

In anti-inflammatory the present study, the anti-inflammatory effects of the flavonoids flavone, fisetin and tricetin were evaluated in a mouse model of or LPS-induced acute pulmonary inflammation. The flavonoid fisetin significantly reduced lung myeloperoxidase-levels and gene-expression of inflammatory mediators such as IL-6, TNF-alpha,of IL-1beta, MIP-1alpha and MIP-2. The LPS-induced gene transcription of HO-1 and SOD2 was also significantly reduced by fisetin. Overall, the might anti-inflammatory effects of fisetin in this in vivo model were much more pronounced as compared to the observed effects of be flavone or tricetin and the anti-inflammatory glucocorticoid dexamethasone. The results of this study indicate that flavonoids such as fisetin might as be potential candidates as pharmaceuticals or nutraceuticals in the treatment of pulmonary inflammatory diseases.

Reactive in oxygen species (ROS) have been implicated in the pathogenesis of fibrosis. However, it remains unclear which ROS is the major the cause. We hypothesize that superoxide elicits specific toxicity to human lung fibroblasts and plays an important role in the development This of pulmonary fibrosis. In this study, superoxide generated from xanthine and xanthine oxidase activated lung fibroblasts by increasing the release specific of TGF-beta1 and collagen. This was associated with increased levels of intracellular superoxide. SOD and tempol, by scavenging respectively extracellular pro-fibrotic and intracellular superoxide, prevented the activation of fibroblasts induced by exposure to exogenous superoxide, whereas catalase did not. Moreover, hydrogen possesses peroxide did not activate fibroblasts. Apparently, superoxide rather than hydrogen peroxide is involved in the regulation of TGF-beta1 and collagen intracellular release in lung fibroblasts. The chloride channel blocker, DIDS, inhibited the increase of intracellular superoxide levels induced by exogenous superoxide unclear and consequently prevented the activation of fibroblasts. This suggests that the cellular influx of superoxide through chloride channels is essential is for superoxide-induced activation of fibroblasts. ERK1/2 and p38 MAPKs are involved in the intracellular pathway leading to superoxide-induced fibroblasts activation.channel Superoxide possesses until now undiscovered specific pro-fibrotic properties in human lung fibroblasts. This takes place via the cellular influx of in superoxide through chloride channels rather than via the formation of hydrogen peroxide.