TY - GEN A1 - Schmiedchen, Bettina A1 - Longardt, Ann Carolin A1 - Bührer, Christoph A1 - Raila, Jens A1 - Loui, Andrea A1 - Schweigert, Florian J. T1 - The Relative Dose Response Test Based on Retinol-Binding Protein 4 Is Not Suitable to Assess Vitamin A Status in Very Low Birth Weight Infants N2 - Background: The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes. Objectives: This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants. Methods: This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations. Results: The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27% (8.4-42.5) and the median RBP4-RDR was 8.4% (-3.4 to 27.9), compared to 7.5% (-10.6 to 20.8) and -0.61% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18). Conclusion: The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 342 KW - relative dose response test KW - vitamin A KW - preterm infant Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-399853 ER - TY - GEN A1 - Castro, José Pedro A1 - Grune, Tilman A1 - Speckmann, Bodo T1 - The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction N2 - White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho)physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e.g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 339 KW - adipogenesis KW - adipose tissue dysregulation KW - antioxidants KW - metabolic disorders KW - oxidative stress Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-398039 ER - TY - THES A1 - Marschall, Talke Anu T1 - Zytotoxizität, Bioverfügbarkeit und Metabolismus kleiner Selenspezies in humanen Zellen und Entwicklung von ICP-QQQ-MS-basierten Methoden für deren Nachweis Y1 - 2017 ER - TY - GEN A1 - Gerecke, Christian A1 - Edlich, Alexander A1 - Giulbudagian, Michael A1 - Schumacher, Fabian A1 - Zhang, Nan A1 - Said, Andre A1 - Yealland, Guy A1 - Lohan, Silke B. A1 - Neumann, Falko A1 - Meinke, Martina C. A1 - Ma, Nan A1 - Calderón, Marcelo A1 - Hedtrich, Sarah A1 - Schäfer-Korting, Monika A1 - Kleuser, Burkhard T1 - Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes N2 - Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 335 KW - Drug delivery KW - nanoparticles KW - particle characterization KW - keratinocytes KW - nanotoxicology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-395325 ER -