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Wjst M.,Institute of Lung Biology and Disease ILBD | Wjst M.,TU Munich
Current Opinion in Allergy and Clinical Immunology | Year: 2012

Purpose of Review: A link between vitamin D supplementation and allergy was already suspected soon after it became possible to chemically synthesise vitamin D2 by means of ultraviolet radiation. During the past decade, the assumed allergenic effect was confirmed by clinical and epidemiological studies although the most recent discussion has centred more on vitamin D insufficiency. The purpose of this review is to summarise studies published during the past year while attempting to reconcile some apparent inconsistencies. Recent Findings: Two new concepts are presented here - epigenetic programming of the fetal vitamin D system by low maternal vitamin D supply (Barker's paradox) and ubiquitous vitamin D exposure of the newborn (Rose's paradox). Taken together a misdirected epigenetic programming offers an explanation why also vitamin D insufficiency in pregnancy may be associated with increased allergy rates in the offspring.At least eight studies examined the association of early 25-hydroxy-vitamin D levels and atopic diseases in 2011, whereas no new study addressed the question of vitamin D supplementation in the newborn period. One study tested the whole range of 25-hydroxy-vitamin D levels in cord blood describing a U-shaped association with 2.4-fold odds ratio of low and 4-fold odds ratio of high levels to develop allergen-specific immunoglobulin E. Summary: Randomised clinical trials with vitamin D supplements are therefore highly required. Several key points are presented for designing vitamin D trials. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Schamberger A.C.,Ludwig Maximilians University of Munich | Mise N.,Ludwig Maximilians University of Munich | Meiners S.,Ludwig Maximilians University of Munich | Eickelberg O.,Ludwig Maximilians University of Munich | Eickelberg O.,Institute of Lung Biology and Disease ILBD
Expert Opinion on Drug Discovery | Year: 2014

Introduction: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The growing burden of COPD is due to continuous tobacco use, which is the most important risk factor of the disease, indoor fumes, occupational exposures and also aging of the world's population. Epigenetic mechanisms significantly contribute to COPD pathophysiology. Areas covered: This review focuses on disease-relevant changes in DNA modification, histone modification and non-coding RNA expression in COPD, and provides insight into novel therapeutic approaches modulating epigenetic mechanisms. Recent findings revealed, among others, globally changed DNA methylation patterns, decreased levels of histone deacetylases and reduced microRNAs levels in COPD. The authors also discuss a potential role of the chromatin silencing Polycomb group of proteins in COPD. Expert opinion: COPD is a highly complex disease and therapy development is complicated by the fact that many smokers develop both COPD and lung cancer. Of interest, combination therapies involving DNA methyltransferase inhibitors and anti-inflammatory drugs provide a promising approach, as they might be therapeutic for both COPD and cancer. Although the field of epigenetic research has virtually exploded over the last 10 years, particular efforts are required to enhance our knowledge of the COPD epigenome in order to successfully establish epigenetic-based therapies for this widespread disease. © 2014 Informa UK, Ltd. Source

Moller W.,Institute of Lung Biology and Disease ILBD | Gibson N.,European Commission - Joint Research Center Ispra | Geiser M.,University of Bern | Pokhrel S.,University of Bremen | And 11 more authors.
Journal of Nanoparticle Research | Year: 2013

The intensive use of nano-sized particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of nanoparticles (NP) with biological systems after various routes of exposure needs to be investigated using well-characterized NP. We report here on the generation of gold-NP (Au-NP) aerosols for inhalation studies with the spark ignition technique, and their characterization in terms of chemical composition, physical structure, morphology, and specific surface area, and on interaction with lung tissues and lung cells after 1 h inhalation by mice. The originally generated agglomerated Au-NP were converted into compact spherical Au-NP by thermal annealing at 600 C, providing particles of similar mass, but different size and specific surface area. Since there are currently no translocation data available on inhaled Au-NP in the 10-50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation in rodents. For anticipated in vivo systemic translocation and dosimetry analyses, radiolabeled Au-NP were created by proton irradiating the gold electrodes of the spark generator, thus forming gamma ray emitting 195Au with 186 days half-life, allowing long-term biokinetic studies. The dissolution rate of 195Au from the NP was below detection limits. The highly concentrated, polydisperse Au-NP aerosol (1-2 × 107 NP/cm 3) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation and number concentration. After collection on filters particles can be re-suspended and used for instillation or ingestion studies. © 2013 Springer Science+Business Media Dordrecht. Source

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