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Andersen G.,German Research Center for Food Chemistry | Burkon A.,German Research Center for Food Chemistry | Sulzmaier F.J.,German Research Center for Food Chemistry | Walker J.M.,University of Vienna | And 5 more authors.
Molecular Nutrition and Food Research | Year: 2011

Scope: trans-Resveratrol has been shown to improve insulin sensitivity and to enhance cellular glucose uptake. Evidence from recent studies indicates that these effects depend on SIRT1-pathways. Methods and results: Since ingestion of resveratrol leads to the presence of resveratrol and resveratrol metabolites in the body, we aimed at investigating (i) whether a daily dose of 300mg resveratrol/kg body weight in healthy male Wistar rats for a period of 8wk affects the selected parameters of glucose and lipid metabolism and (ii) whether the resulting plasma concentrations of resveratrol metabolites were effective in modulating SIRT1 expression. The dietary dose was based on the results from preceding toxicity studies. The results from the feeding experiment revealed plasma concentrations of resveratrol and its metabolites below 1μmol/L and showed that fasting glucose and insulin levels were decreased by 35 and 41%, respectively, in the resveratrol group compared with controls. Insulin sensitivity was enhanced by 70%, whereas liver SIRT1 protein expression was not affected. Treatment of HepG2 cells with 10μM resveratrol (1.49-fold) or its diglucuronides (1.21-fold) increased SIRT1 expression. Conclusion: These results suggest that the improved insulin sensitivity after dietary administration of 300mg resveratrol/kg body weight does not involve increased protein expression of SIRT1. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Wang J.,Leibniz Institute for Age Research | Wang J.,Friedrich - Schiller University of Jena | Lu X.,University of Regensburg | Sakk V.,Leibniz Institute for Age Research | And 4 more authors.
Blood | Year: 2014

Telomere shortening limits the proliferative capacity of human cells, and age-dependent shortening of telomeres occurs in somatic tissues including hematopoietic stem cells (HSCs). It is currently unknown whether genomic and molecular damage that occurs in HSCs induced by telomere shortening is transmitted to the progenitor cells. Here we show that telomere shortening results in DNA damage accumulation and gene expression changes in quiescent HSCs of aged mice. Upon activation, a subset of HSCs with elevated levels of DNA damage and p16 expression are blocked from cell cycle entry, and apoptosis is induced in HSCs entering the cell cycle. Activation of both checkpoints associates with normalization of DNA damage and gene expression profiles at early progenitor stages. These findings indicate that quiescent HSCs have an elevated tolerance to accumulate genomic alterations in response to telomere shortening, but the transmission of these aberrations to the progenitor cell level is prevented by senescence and apoptosis. © 2014 by The American Society of Hematology. Source

Su Z.-H.,Peking Union Medical College | Zou G.-A.,Peking Union Medical College | Preiss A.,Fraunhofer Institute For Toxikologie Und Experimentelle Medizin | Zhang H.-W.,Peking Union Medical College | Zou Z.-M.,Peking Union Medical College
Journal of Pharmaceutical and Biomedical Analysis | Year: 2010

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula containing seven herbal medicines, has been used in treatment of gastritis, peptic ulcer, irritable bowel syndrome and depression clinically. However, the chemical constituents in CSGS had not been studied so far. To quickly identify the chemical constituents of CSGS and to understand the chemical profiles related to antioxidant activity of CSGS, liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap (LC-LTQ-Orbitrap) mass spectrometry has been applied for online identification of chemical constituents in complex system, meanwhile, antioxidant profile of CSGS was investigated by the fraction collecting and microplate reading system. As a result, 33 chemical constituents in CSGS were identified. Among them, 13 components could be detected both in positive and in negative ion modes, 20 constituents were determined only in positive ion mode and 2 components were only detected in negative ion mode. Meanwhile, the potential antioxidant profile of CSGS was also characterized by combination of 96-well plate collection of elutes from HPLC analysis and microplate spectrophotometer, in which the scavenging activities of free radical produced by DPPH of each fraction could be directly investigated by the analysis of microplate reader. This study quickly screened the contribution of CSGS fractions to the antioxidant activity and online identified the corresponding active constituents. The results indicated that the combination of LC-MSn and 96-well plate assay system established in this paper would be a useful strategy for correlating the chemical profile of TCMs with their bioactivities without isolation and purification. © 2010. Source

Koczulla A.R.,University of Marburg | Koczulla A.R.,Universitatsklinikum Giessen und Marburg | Hattesohl A.,University of Marburg | Biller H.,Fraunhofer Institute For Toxikologie Und Experimentelle Medizin | And 8 more authors.
Pneumologie | Year: 2011

Non-invasive pulmonary diagnostics is a promising and interesting field in respiratory medicine. Beside exhaled breath condensate, there is an increasing interest in alternative and faster techniques such as electronic noses (EN). EN aim to mimic or improve the sense of smelling. Different types of EN have been employed in research so far. In addition to ion mobility spectrometry and mass spectrometry, ENs that consist of various biopolymer sensors for the sensing of volatile organic compounds (VOCs) have been tested. VOCs bind to the sensors depending on size, structure, hydrogen binding and polarity. This leads to physical alterations, e.g., swelling resulting in a change of resistance. The smell print represents composite patterns in contrast to single compounds, and the distinction between different categories is achieved by pattern recognition algorithms. Other types of EN like mass spectrometry and ion mobility spectrometry are capable of identifying even single analyte fractions provided that their characteristics have been saved in data repositories. The non-invasive nature, onsite availability and relatively cheap sampling are advantages of ENs that underly the increasing interest in their use for medical purposes. Some promising results have already been published. This review aims to describe the state of the art in brief form. © Georg Thieme Verlag KG Stuttgart New York. Source

Kornmann O.,University Hospital Mainz | Watz H.,Pulmonary Research Institute at LungenClinic Grosshansdorf | Fuhr R.,Parexel International | Krug N.,Fraunhofer Institute For Toxikologie Und Experimentelle Medizin | And 2 more authors.
Pulmonary Pharmacology and Therapeutics | Year: 2014

Background: When first approved in the European Union (EU), the omalizumab dosing table had upper bodyweight and IgE limits of 150kg and 700IU/mL, respectively. In this study, we assessed the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of omalizumab in patients with IgE/bodyweight combinations above those in the original dosing table. Methods: A multicentre, open-label, parallel-group study assessed the safety, PK and PD of omalizumab in 32 patients with mild-to-moderate allergic (IgE-mediated) asthma. Patients received two subcutaneous injections of omalizumab at one of three dosage levels (450, 525, or 600mg), chosen according to baseline IgE (300-2000IU/mL) and bodyweight (40-150kg), with a 14-day interval between injections. Results: Overall, 69 adverse events (AEs), none of them serious, were reported by 26 (81.3%) patients. Analysis of laboratory measurements, vital signs and ECG data revealed no adverse findings of clinical relevance. The PK profile was consistent with previous data for lower doses. Mean maximum decrease of free IgE from screening was ≥99% for all three doses, and mean free IgE concentrations remained <25ng/mL for at least 2 weeks after the second dose. The reductions in free IgE were consistent with levels previously associated with clinical improvements. Conclusions: The safety and PK/PD findings from this study are consistent with previous data, and supported the extension of the omalizumab dosing table to include those patients with higher IgE/bodyweight combinations.Clinical trial registry and registration number: clinicaltrials.gov (NCT00546143). © 2014 The Authors. Source

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