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 - JOUR A1 - Raila, Jens A1 - Kawashima, Chiho A1 - Sauerwein, Helga A1 - Hülsmann, Nadine A1 - Knorr, Christoph A1 - Myamoto, Akio A1 - Schweigert, Florian J. T1 - Validation of blood vitamin A concentrations in cattle: comparison of a new cow-side test (iCheck™ FLUORO) with high-performance liquid chromatography (HPLC) JF - BMC veterinary research N2 - Background: Plasma concentration of retinol is an accepted indicator to assess the vitamin A (retinol) status in cattle. However, the determination of vitamin A requires a time consuming multi-step procedure, which needs specific equipment to perform extraction, centrifugation or saponification prior to high-performance liquid chromatography (HPLC). Methods: The concentrations of retinol in whole blood (n = 10), plasma (n = 132) and serum (n = 61) were measured by a new rapid cow-side test (iCheck™ FLUORO) and compared with those by HPLC in two independent laboratories in Germany (DE) and Japan (JP). Results: Retinol concentrations in plasma ranged from 0.033 to 0.532 mg/L, and in serum from 0.043 to 0.360 mg/L (HPLC method). No significant differences in retinol levels were observed between the new rapid cow-side test and HPLC performed in different laboratories (HPLC vs. iCheck™ FLUORO: 0.320 ± 0.047 mg/L vs. 0.333 ± 0.044 mg/L, and 0.240 ± 0.096 mg/L vs. 0.241 ± 0.069 mg/L, lab DE and lab JP, respectively). A similar comparability was observed when whole blood was used (HPLC vs. iCheck™ FLUORO: 0.353 ± 0.084 mg/L vs. 0.341 ± 0.064 mg/L). Results showed a good agreement between both methods based on correlation coefficients of r2 = 0.87 (P < 0.001) and Bland-Altman blots revealed no significant bias for all comparison. Conclusions: With the new rapid cow-side test (iCheck™ FLUORO) retinol concentrations in cattle can be reliably assessed within a few minutes and directly in the barn using even whole blood without the necessity of prior centrifugation. The ease of the application of the new rapid cow-side test and its portability can improve the diagnostic of vitamin A status and will help to control vitamin A supplementation in specific vitamin A feeding regimes such as used to optimize health status in calves or meat marbling in Japanese Black cattle. KW - Cattle KW - Vitamin A KW - Biomarker KW - Blood KW - Method comparison KW - Cow-side assay Y1 - 2017 U6 - https://doi.org/10.1186/s12917-017-1042-3 VL - 13 PB - BioMed Central CY - London ER - TY - THES A1 - Stadion, Mandy T1 - Validation and Characterization of lfi202b and Zfp69, two Novel Disease Genes in Obesity-Associated Insulin Resistance Y1 - 2017 ER - TY - JOUR A1 - Wallmeyer, Leonie A1 - Dietert, Kristina A1 - Sochorova, Michaela A1 - Gruber, Achim D. A1 - Kleuser, Burkhard A1 - Vavrova, Katerina A1 - Hedtrich, Sarah T1 - TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents JF - Scientific reports N2 - Mutations in the gene encoding for filaggrin (FLG) are major predisposing factors for atopic dermatitis (AD). Besides genetic predisposition, immunological dysregulations considerably contribute to its pathophysiology. For example, thymic stromal lymphopoietin (TSLP) is highly expressed in lesional atopic skin and significantly contributes to the pathogenesis of AD by activating dendritic cells that then initiate downstream effects on, for example, T cells. However, little is known about the direct interplay between TSLP, filaggrin-deficient skin and other immune cells such as T lymphocytes. In the present study, FLG knockdown skin equivalents, characterised by intrinsically high TSLP levels, were exposed to activated CD4(+) T cells. T cell exposure resulted in an inflammatory phenotype of the skin equivalents. Furthermore, a distinct shift from a Th1/Th17 to a Th2/Th22 profile was observed following exposure of T cells to filaggrin-deficient skin equivalents. Interestingly, TSLP directly stimulated T cell migration exclusively in filaggrin-deficient skin equivalents even in the absence of dendritic cells, indicating a hitherto unknown role of TSLP in the pathogenesis of AD. Y1 - 2017 U6 - https://doi.org/10.1038/s41598-017-00670-2 SN - 2045-2322 VL - 7 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Marschall, Talke Anu A1 - Kroepfl, Nina A1 - Jensen, Kenneth Bendix A1 - Bornhorst, Julia A1 - Meermann, B. A1 - Kühnelt, Doris A1 - Schwerdtle, Tanja T1 - Tracing cytotoxic effects of small organic Se species in human liver cells back to total cellular Se and Se metabolites JF - Metallomics N2 - Small selenium (Se) species play a major role in the metabolism, excretion and dietary supply of the essential trace element selenium. Human cells provide a valuable tool for investigating currently unresolved issues on the cellular mechanisms of Se toxicity and metabolism. In this study, we developed two isotope dilution inductively coupled plasma tandem-mass spectrometry based methods and applied them to human hepatoma cells (HepG2) in order to quantitatively elucidate total cellular Se concentrations and cellular Se species transformations in relation to the cytotoxic effects of four small organic Se species. Species-and incubation time-dependent results were obtained: the two major urinary excretion metabolites trimethylselenonium (TMSe) and methyl-2-acetamido-2-deoxy-1-seleno-beta- D-galactopyranoside (SeSugar 1) were taken up by the HepG2 cells in an unmodified manner and did not considerably contribute to the Se pool. In contrast, Se-methylselenocysteine (MeSeCys) and selenomethionine (SeMet) were taken up in higher amounts, they were largely incorporated by the cells (most likely into proteins) and metabolized to other small Se species. Two new metabolites of MeSeCys, namely gamma-glutamyl-Se-methylselenocysteine and Se-methylselenoglutathione, were identified by means of HPLC-electrospray-ionization-Orbitrap-MS. They are certainly involved in the (de-) toxification modes of Se metabolism and require further investigation. Y1 - 2017 U6 - https://doi.org/10.1039/c6mt00300a SN - 1756-5901 SN - 1756-591X VL - 9 SP - 268 EP - 277 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Witt, Barbara A1 - Meyer, Sören A1 - Ebert, Franziska A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons JF - Archives of toxicology : official journal of EUROTOX N2 - Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly’s brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized. KW - Arsenolipids KW - Neurons KW - Cytotoxicity KW - Neurotoxicity KW - Arsenic-containing hydrocarbons KW - Arsenic-containing fatty acids Y1 - 2017 U6 - https://doi.org/10.1007/s00204-017-1933-x SN - 0340-5761 SN - 1432-0738 VL - 91 SP - 3121 EP - 3134 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Strehlau, Jenny A1 - Weber, Till A1 - Luerenbaum, Constantin A1 - Bornhorst, Julia A1 - Galla, Hans-Joachim A1 - Schwerdtle, Tanja A1 - Winter, Martin A1 - Nowak, Sascha T1 - Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials JF - Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica N2 - A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5-12.9%. It could be shown that no matrix effects were present and recovery rates between 98 and 104% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place. KW - Liquid-liquid extraction KW - GC-MS KW - Lithiumion battery (LIB) KW - Organic carbonates KW - Cell culture materials Y1 - 2017 U6 - https://doi.org/10.1007/s00216-017-0549-6 SN - 1618-2642 SN - 1618-2650 VL - 409 SP - 6123 EP - 6131 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Khozroughi, Amin Ghadiri A1 - Jander, Elisabeth A1 - Schirrmann, Michael A1 - Rawel, Harshadrai Manilal A1 - Kroh, Lothar W. A1 - Schlueter, Oliver T1 - The role of myoglobin degradation in the formation of zinc protoporphyrin IX in the longissimus lumborum of pork JF - LWT - food science and technology : an official journal of the Swiss Society of Food Science and Technology (SGLWT/SOSSTA) and the International Union of Food Science and Technology (IUFoST) N2 - Investigations on the post mortal formation of fluorescent zinc protoporphyrin (ZnPP) IX in pork meat are currently in focus of meat science research. The role of myoglobin degradation in this context appears to be one of the most diversely discussed issues. To address this question meat-extracts of longissimus lumborum (LL) muscle (0.8 mg/mL) were incubated at 30 degrees C for up to 72 h and investigated by HPSEC-UV-fluorescence, SDS-PAGE and MALDI-TOF-MS. Between 0 and 72 h of incubation the fluorescence intensity (lambda(ex)./(em). = 420/590 nm) of the meat-extracts rose significantly (p < 0.001) from 10.9 +/- 0.8 to 34.8 +/- 0.3 (rel. units) while the staining intensity of the SDS-PAGE of myoglobin non-significantly (p > 0.4) changed from 6.2 +/- 0.5 x 105 to 5.0 +/- 0.3 x 105 (rel. units). The results indicate that ZnPP is formed by a Fe(II)-Zn(II)-substitution in myoglobin heme where an accompanying myoglobin degradation is not necessarily obligatory. (C) 2017 Elsevier Ltd. All rights reserved. KW - Meat KW - Fluorescence KW - Proteolysis KW - Post mortem chemistry Y1 - 2017 U6 - https://doi.org/10.1016/j.lwt.2017.06.047 SN - 0023-6438 SN - 1096-1127 VL - 85 SP - 22 EP - 27 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Berger, Beatrice A1 - Baldermann, Susanne A1 - Ruppel, Silke T1 - The plant growth-promoting bacterium Kosakonia radicincitans improves fruit yield and quality of Solanum lycopersicum JF - Journal of the Science of Food and Agriculture N2 - BACKGROUNDProduction and the quality of tomato fruits have a strong economic relevance. Microorganisms such as the plant growth-promoting bacterium (PGPB) Kosakonia radicincitans (DSM 16656) have been demonstrated to improve shoot and root growth of young tomato plants, but data on yield increase and fruit quality by K. radicincitans are lacking. RESULTSThis study investigated how K. radicincitans affects tomato fruits. After inoculation of tomato seeds with K. radicincitans or a sodium chloride buffer control solution, stalk length, first flowering and the amount of ripened fruits produced by inoculated and non-inoculated plants were monitored over a period of 21 weeks. Inoculation of tomato seeds with K. radicincitans accelerated flowering and ripening of tomato fruits. Sugars, acidity, amino acids, volatile organic compounds and carotenoids in the fruits were also analyzed. CONCLUSIONIt was found that the PGPBK. radicincitans affected the amino acid, sugar and volatile composition of ripened fruits, contributing to a more pleasant-tasting fruit without forfeiting selected quality indicators. (c) 2017 Society of Chemical Industry KW - plant growth-promoting bacteria KW - Kosakonia radicincitans KW - fruit metabolites KW - Solanum lycopersicum Y1 - 2017 U6 - https://doi.org/10.1002/jsfa.8357 SN - 0022-5142 SN - 1097-0010 VL - 97 SP - 4865 EP - 4871 PB - Wiley CY - Hoboken ER - TY - THES A1 - Rödiger, Maria T1 - The Impact of the ARFRP1 Action at the Golgi Apparatus on Adipocyte Function Y1 - 2017 ER - TY - JOUR A1 - Meyer, Sören A1 - Lopez-Serrano, Aniceto A1 - Mitze, Hanna A1 - Jakubowski, Norbert A1 - Schwerdtle, Tanja T1 - Single-cell analysis by ICP-MS/MS as a fast tool for cellular bioavailability studies of arsenite JF - Metallomics : integrated biometal science N2 - Single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) has become a powerful and fast tool to evaluate the elemental composition at a single-cell level. In this study, the cellular bioavailability of arsenite (incubation of 25 and 50 mu M for 0-48 h) has been successfully assessed by SC-ICP-MS/MS for the first time directly after re-suspending the cells in water. This procedure avoids the normally arising cell membrane permeabilization caused by cell fixation methods (e.g. methanol fixation). The reliability and feasibility of this SC-ICP-MS/MS approach with a limit of detection of 0.35 fg per cell was validated by conventional bulk ICP-MS/MS analysis after cell digestion and parallel measurement of sulfur and phosphorus. Y1 - 2017 U6 - https://doi.org/10.1039/c7mt00285h SN - 1756-5901 SN - 1756-591X VL - 10 IS - 1 SP - 73 EP - 76 PB - Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Halibasic, Emina A1 - Fuerst, Elisabeth A1 - Heiden, Denis A1 - Japtok, Lukasz A1 - Diesner, Susanne C. A1 - Hillebrand, P. A1 - Trauner, Michael A1 - Kleuser, Burkhard A1 - Kazemi-Shirazi, Lili A1 - Untersmayr, Eva T1 - Significantly reduced plasma levels of the bioactive sphingolipid S1P in lung transplanted cystic fibrosis patients are associated with gastrointestinal symptoms T2 - Allergy Y1 - 2017 SN - 0105-4538 SN - 1398-9995 VL - 72 IS - S103 SP - 195 EP - 195 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Yang, Xiaoping A1 - Darko, Kwame Oteng A1 - Huang, Yanjun A1 - He, Caimei A1 - Yang, Huansheng A1 - He, Shanping A1 - Li, Jianzhong A1 - Li, Jian A1 - Hocher, Berthold A1 - Yin, Yulong T1 - Resistant starch regulates gut microbiota BT - structure, biochemistry and cell signalling JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Starch is one of the most popular nutritional sources for both human and animals. Due to the variation of its nutritional traits and biochemical specificities, starch has been classified into rapidly digestible, slowly digestible and resistant starch. Resistant starch has its own unique chemical structure, and various forms of resistant starch are commercially available. It has been found being a multiple-functional regulator for treating metabolic dysfunction. Different functions of resistant starch such as modulation of the gut microbiota, gut peptides, circulating growth factors, circulating inflammatory mediators have been characterized by animal studies and clinical trials. In this mini-review, recent remarkable progress in resistant starch on gut microbiota, particularly the effect of structure, biochemistry and cell signaling on nutrition has been summarized, with highlights on its regulatory effect on gut microbiota. KW - Resistant starch KW - Gut microbiota KW - Nutrition Y1 - 2017 U6 - https://doi.org/10.1159/000477386 SN - 1015-8987 SN - 1421-9778 VL - 42 IS - 1 SP - 306 EP - 318 PB - Karger CY - Basel ER - TY - GEN A1 - Hocher, Berthold A1 - Tsuprykov, Oleg T1 - Renoprotective effects of GLP1R agonists and SGLT2 inhibitors T2 - Nature reviews nephroloy N2 - New data from the LEADER trial show that the glucagon-like peptide 1 receptor agonist liraglutide protects against diabetic nephropathy in patients with type 2 diabetes mellitus. The renoprotective efficacy of liraglutide is not, however, as great as that reported for the sodium-glucose cotransporter 2 inhibitor emplagiflozin in the EMPA-REG OUTCOME trial. Y1 - 2017 U6 - https://doi.org/10.1038/nrneph.2017.140 SN - 1759-5061 SN - 1759-507X VL - 13 SP - 728 EP - 729 PB - Nature Publ. Group CY - New York ER - TY - THES A1 - Schraplau, Anne T1 - Regulation der Expression von Xenobiotika-metabolisierenden Enzymen und Deiodasen durch die Xenobiotika-abhängige wechselseitige Induktion von Xenosensor-Transkriptionsfaktoren und Prostaglandin E2 BT - Auswirkung auf die Aktivierung und Inaktivierung von Schilddrüsenhormonen Y1 - 2017 ER - TY - JOUR A1 - Kröpfl, Nina A1 - Marschall, Talke A. A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja A1 - Kuehnelt, Doris T1 - Quantitative determination of the sulfur-containing antioxidant ergothioneine by HPLC/ICP- QQQ-MS JF - Journal of Analytical Atomic Spectrometry N2 - Interest in the sulfur-containing antioxidant ergothioneine calls for reliable analytical methods for its quantification. In this work, a method based on reversed-phase high performance liquid chromatography (RP-HPLC) coupled with elemental mass spectrometry detection in mass shift mode (inductively coupled plasma triple quadrupole mass spectrometry, ICP-QQQ-MS) using oxygen as the reaction gas was developed for the element-selective determination of ergothioneine in complex biological matrices. Application of an instrumental setup using a 6-port-valve and the introduction of a methanol gradient allowed the time-efficient analysis of samples containing strongly retained sulfur species besides ergothioneine without compromising ICPMS detection. In aqueous solution, limits of detection and quantification (LOD and LOQ) of the optimized method for m/z 32 -> 48 (SO+) were 0.23 mu g S per L and 0.80 mu g S per L, respectively; measurements in a complex matrix (human hepatocyte carcinoma cells, HepG2) resulted in an LOD of 0.6 mu g S per L and an LOQ of 2.3 mu g S per L. Recoveries of ergothioneine from cell pellets spiked with the analyte before cell lysis (97 +/- 3%) matched those obtained for cell culture medium spiked before syringe filtration (96 +/- 9%) demonstrating that sample preparation did not impair the quantitative determination of ergothioneine. When HepG2 cells were exposed to ergothioneine via the culture medium, they showed low absorption; approximately 3% of the added ergothioneine was found in cell lysates, while most of it (>= 85%) remained in the cell culture medium. The method is capable of separating ergothioneine from other biologically relevant sulfur-containing species and is expected to be of broad future use. Furthermore, the potential use for the simultaneous separation of selenium species, thereby extending the scope of possible applications, was demonstrated by applying it to water extracts of oyster mushrooms. Y1 - 2017 U6 - https://doi.org/10.1039/c7ja00030h SN - 0267-9477 SN - 1364-5544 VL - 32 SP - 1571 EP - 1581 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Reichetzeder, Christoph A1 - Heunisch, Fabian A1 - von Einem, Gina-Franziska A1 - Tsuprykov, Oleg A1 - Kellner, Karl-Heinz A1 - Dschietzig, Thomas A1 - Kretschmer, Axel A1 - Hocher, Berthold T1 - Pre-interventional kynurenine predicts medium-term outcome after contrast media exposure due to coronary angiography JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft N2 - Background/Aims: Contrast induced acute kidney injury (CI-AKI) remains a serious complication of contrast media enhanced procedures like coronary angiography. There is still a lack of established biomarkers that help to identify patients at high risk for short and long-term complications. The aim of the current study was to evaluate plasma kynurenine as a predictive biomarker for CI-AKI and long-term complications, measured by the combined endpoint "major adverse kidney events" (MAKE) up to 120 days after CM application. Methods: In this prospective cohort study 245 patients undergoing coronary angiography were analyzed. Blood samples were obtained at baseline, 24h and 48h after contrast media (CM) application to diagnose CI-AKI. Patients were followed for 120 days for adverse clinical events including death, the need for dialysis, and a doubling of plasma creatinine. Occurrence of any of these events was summarized in the combined endpoint MAKE. Results: Preinterventional plasma kynurenine was not associated with CI-AKI. Patients who later developed MAKE displayed significantly increased preinterventional plasma kynurenine levels (p<0.0001). ROC analysis revealed that preinterventional kynurenine is highly predictive for MAKE (AUC=0.838; p<0.0001). The optimal cutoff was found at >= 3.5 mu mol/L. Using this cutoff, the Kaplan-Meier estimator demonstrated that concentrations of plasma kynurenine >= 3.5 mu mol/L were significantly associated with a higher prevalence of MAKE until follow up (p<0.0001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. Conclusion: Preinterventional plasma kynurenine might serve as a highly predictive biomarker for MAKE up to 120 days after coronary angiography. KW - Contrast induced acute kidney injury KW - Coronary angiography KW - Major adverse kidney event KW - Kynurenine KW - Preinterventional biomarker Y1 - 2017 U6 - https://doi.org/10.1159/000477222 SN - 1420-4096 SN - 1423-0143 VL - 42 IS - 2 SP - 244 EP - 256 PB - Karger CY - Basel ER - TY - JOUR A1 - Lu, Yong-Ping A1 - Hasan, Ahmed A. A1 - Zeng, Shufei A1 - Hocher, Berthold T1 - Plasma ET-1 concentrations are elevated in pregnant women with hypertension - meta-analysis of clinical studies JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft N2 - Background/Aims: The ET system might be involved in the pathogenesis of hypertensive disorders during pregnancy. The objective is to analyse the impact of ET-1 in hypertensive pregnant women by a strict meta-analysis of published human clinical studies. Methods: Based on the principle of Cochrane systematic reviews, Cohort studies in PubMed (Medline), Google Scholar and China Biological Medicine Database (CBM-disc) designed to identify the role of endothelin-1 (ET-1) in the pathophysiology of gestational hypertension and preeclampsia were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects model. Results: Sixteen published cohort studies including 1739 hypertensive cases and 409 controls were used in the meta-analysis. ET-1 plasma concentrations were higher in hypertensive pregnant women as compared to the controls (mean difference between groups: 19.02 [15.60～22.44], P < 0.00001,). These finding were driven by severity of hypertension and/or degree of proteinuria. Conclusion: Plasma ET-1 concentrations are elevated in hypertensive disorders during human pregnancy. In particular women with preeclampsia (hypertensive pregnant women with proteinuria) have substantially elevated plasma ET-1 concentration as compared to pregnant women with normal blood pressure. KW - Et-1 KW - Pregnancy KW - Hypertension KW - Meta-analysis Y1 - 2017 U6 - https://doi.org/10.1159/000482004 SN - 1420-4096 SN - 1423-0143 VL - 42 IS - 4 SP - 654 EP - 663 PB - Karger CY - Basel ER - TY - JOUR A1 - Xu, Mei A1 - Lu, Yong-Ping A1 - Hasan, Ahmed A. A1 - Hocher, Berthold T1 - Plasma ET-1 concentrations are elevated in patients with hypertension meta-analysis of clinical studies JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft N2 - Background/Aims: A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies. Methods: We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks. Based on the principle of Cochrane systematic reviews, case control studies (CCSs) in PubMed (Medline) and Google Scholar designed to identify the role of endothelin-1 (ET-1) in the pathophysiological of hypertension were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects models. Results: Eleven studies fulfilling our in-and exclusion criteria were eligible for this meta-analysis. These studies included 450 hypertensive patients and 328 controls. Our meta-analysis revealed that ET-1 plasma concentrations were higher in hypertensive patients as compared to the control patients [mean difference between groups 1.57 pg/mL, 95%Ci [0.47 similar to 2.68, P = 0.005]. These finding were driven by patients having systolic blood pressure higher than 160 mmHg and diastolic blood pressure higher than 100 mmHg. Conclusions: This meta-analysis showed that hypertensive patients do have elevated plasma ET-1 concentrations. This finding is driven by those patients with high systolic/diastolic blood pressure. Given that the ET-1 gene did not appear in any of the whole genome association studies searching for hypertension associated gene loci, it is very likely that the elevated plasma ET-1 concentrations in hypertensive patients are secondary to hypertension and may reflect endothelial cell damage. KW - Hypertension KW - ET-1 KW - Meta-analysis Y1 - 2017 U6 - https://doi.org/10.1159/000477572 SN - 1420-4096 SN - 1423-0143 VL - 42 IS - 2 SP - 304 EP - 313 PB - Karger CY - Basel ER - TY - GEN A1 - Döge, Nadine A1 - Schumacher, Fabian A1 - Balzus, Benjamin A1 - Colombo, Miriam A1 - Hadam, Sabrina A1 - Rancan, Fiorenza A1 - Blume-Peytavi, Ulrike A1 - Kleuser, Burkhard A1 - Bodmeier, Roland A1 - Vogt, Annika T1 - Particle- based formulations and controlled skin barrier disruption have a signifi cant impact on the delivery and penetration kinetics of dexamethasone as assessed in an ex vivo microdialysis T2 - Journal der Deutschen Dermatologischen Gesellschaft N2 - Preclinical assessment of penetration not only in intact, but also in barrier‐disrupted skin is important to explore the surplus value of novel drug delivery systems, which can be specifically designed for diseased skin. Here, we characterized physical and chemical barrier disruption protocols for short‐term ex vivo skin cultures with regard to structural integrity, physiological and biological parameters. Further, we compared the penetration of dexamethasone (Dex) in different nanoparticle‐based formulations in stratum corneum, epidermis and dermis extracts of intact vs. barrier‐disrupted skin as well as by dermal microdialysis at 6, 12 and 24 hours after topical application. Dex was quantified by liquid‐chromatography ‐ tandem‐mass spectrometry (LC‐MS/MS). Simultaneously, we investigated the Dex efficacy by interleukin (IL) analysis. Tape‐stripping (TS) and 4 hours sodium lauryl sulfate 5 % (SLS) exposure were identified as highly effective barrier disruption methods assessed by reproducible transepidermal water loss (TEWL) changes and IL‐6/8 increase which was more pronounced in SLS‐treated skin. The barrier state has also a significant impact on the Dex penetration kinetics: for all formulations, TS highly increased dermal Dex concentration despite the fact that nanocrystals quickly and effectively penetrated both, intact and barrier‐disrupted skin reaching significantly higher dermal Dex concentration after 6 hours compared to Dex cream. The surplus value of encapsulation in ethyl cellulose nanocarriers could mostly be observed when applied on intact skin, in general showing a delayed Dex penetration. Estimation of cytokines was limited due to the trauma caused by probe insertion. In summary, ex vivo human skin is a highly interesting short‐term preclinical model for the analysis of penetration and efficacy of novel drug delivery systems. Y1 - 2017 SN - 1610-0379 SN - 1610-0387 VL - 15 SP - 182 EP - 182 PB - Wiley CY - Berlin ER -