@phdthesis{Toele2013, author = {T{\"o}le, Jonas Claudius}, title = {{\"U}ber die Arc-catFISH-Methode als neues Werkzeug zur Charakterisierung der Geschmacksverarbeitung im Hirnstamm der Maus}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-70491}, school = {Universit{\"a}t Potsdam}, year = {2013}, abstract = {Intensive Forschung hat in den vergangenen Jahrzehnten zu einer sehr detaillierten Charakterisierung des Geschmackssystems der S{\"a}ugetiere gef{\"u}hrt. Dennoch sind mit den bislang eingesetzten Methoden wichtige Fragestellungen unbeantwortet geblieben. Eine dieser Fragen gilt der Unterscheidung von Bitterstoffen. Die Zahl der Substanzen, die f{\"u}r den Menschen bitter schmecken und in Tieren angeborenes Aversionsverhalten ausl{\"o}sen, geht in die Tausende. Diese Substanzen sind sowohl von der chemischen Struktur als auch von ihrer Wirkung auf den Organismus sehr verschieden. W{\"a}hrend viele Bitterstoffe potente Gifte darstellen, sind andere in den Mengen, die mit der Nahrung aufgenommen werden, harmlos oder haben sogar positive Effekte auf den K{\"o}rper. Zwischen diesen Gruppen unterscheiden zu k{\"o}nnen, w{\"a}re f{\"u}r ein Tier von Vorteil. Ein solcher Mechanismus ist jedoch bei S{\"a}ugetieren nicht bekannt. Das Ziel dieser Arbeit war die Untersuchung der Verarbeitung von Geschmacksinformation in der ersten Station der Geschmacksbahn im Mausgehirn, dem Nucleus tractus solitarii (NTS), mit besonderem Augenmerk auf der Frage nach der Diskriminierung verschiedener Bitterstoffe. Zu diesem Zweck wurde eine neue Untersuchungsmethode f{\"u}r das Geschmackssystem etabliert, die die Nachteile bereits verf{\"u}gbarer Methoden umgeht und ihre Vorteile kombiniert. Die Arc-catFISH-Methode (cellular compartment analysis of temporal activity by fluorescent in situ hybridization), die die Charakterisierung der Antwort großer Neuronengruppen auf zwei Stimuli erlaubt, wurde zur Untersuchung geschmacksverarbeitender Zellen im NTS angewandt. Im Zuge dieses Projekts wurde erstmals eine stimulusinduzierte Arc-Expression im NTS gezeigt. Die ersten Ergebnisse offenbarten, dass die Arc-Expression im NTS spezifisch nach Stimulation mit Bitterstoffen auftritt und sich die Arc exprimierenden Neurone vornehmlich im gustatorischen Teil des NTS befinden. Dies weist darauf hin, dass Arc-Expression ein Marker f{\"u}r bitterverarbeitende gustatorische Neurone im NTS ist. Nach zweimaliger Stimulation mit Bittersubstanzen konnten {\"u}berlappende, aber verschiedene Populationen von Neuronen beobachtet werden, die unterschiedlich auf die drei verwendeten Bittersubstanzen Cycloheximid, Chininhydrochlorid und Cucurbitacin I reagierten. Diese Neurone sind vermutlich an der Steuerung von Abwehrreflexen beteiligt und k{\"o}nnten so die Grundlage f{\"u}r divergentes Verhalten gegen{\"u}ber verschiedenen Bitterstoffen bilden.}, language = {de} } @article{SchweigertBaumaneBuchholzetal.1998, author = {Schweigert, Florian J. and Baumane, Anita and Buchholz, Ingeborg and Schoon, Heinz-Adolf}, title = {ß-Carotene accumulation in lung tissue of rats fed different types of fat}, year = {1998}, language = {en} } @phdthesis{Marschall2017, author = {Marschall, Talke Anu}, title = {Zytotoxizit{\"a}t, Bioverf{\"u}gbarkeit und Metabolismus kleiner Selenspezies in humanen Zellen und Entwicklung von ICP-QQQ-MS-basierten Methoden f{\"u}r deren Nachweis}, school = {Universit{\"a}t Potsdam}, pages = {115, VI}, year = {2017}, language = {de} } @article{RailaSchweigert2001, author = {Raila, Jens and Schweigert, Florian J.}, title = {Zur Bedeutung der Nieren im Vitamin-Stoffwechsel}, year = {2001}, language = {de} } @article{BaeslerKoppPohletal.2019, author = {Baesler, Jessica and Kopp, Johannes Florian and Pohl, Gabriele and Aschner, Michael and Haase, Hajo and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans}, series = {Journal of Trace Elements in Medicine and Biology}, volume = {55}, journal = {Journal of Trace Elements in Medicine and Biology}, publisher = {Elsevier}, address = {M{\"u}nchen}, doi = {10.1016/j.jtemb.2019.05.005}, pages = {44 -- 49}, year = {2019}, abstract = {While the underlying mechanisms of Parkinson's disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD.}, language = {en} } @article{BaeslerKoppPohletal.2019, author = {Baesler, Jessica and Kopp, Johannes F. and Pohl, Gabriele and Aschner, Michael and Haase, Hajo and Schwerdtle, Tanja and Bornhorst, Julia}, title = {Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans}, series = {Journal of trace elements in medicine and biology}, volume = {55}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2019.05.005}, pages = {44 -- 49}, year = {2019}, language = {en} } @misc{KilercikUcalSerdaretal.2022, author = {Kilercik, Meltem and Ucal, Yasemin and Serdar, Muhittin and Serteser, Mustafa and Ozpinar, Aysel and Schweigert, Florian J.}, title = {Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity}, series = {Postprints der Universit{\"a}t Potsdam Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam Mathematisch-Naturwissenschaftliche Reihe}, number = {2}, issn = {1866-8372}, doi = {10.25932/publishup-54473}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-544730}, pages = {18}, year = {2022}, abstract = {Background Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation. Methods The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19. Results Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95\% CI 1.019-30.867)) and ZnPP/L ratio (OR (74.313) (95\% CI 1.081-5108.103)). Conclusions For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.}, language = {en} } @article{KilercikUcalSerdaretal.2022, author = {Kilercik, Meltem and Ucal, Yasemin and Serdar, Muhittin and Serteser, Mustafa and Ozpinar, Aysel and Schweigert, Florian J.}, title = {Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity}, series = {PLoS ONE}, volume = {17}, journal = {PLoS ONE}, number = {2}, publisher = {PLOS}, address = {San Francisco, California, US}, issn = {1932-6203}, doi = {10.1371/journal.pone.0262487}, pages = {16}, year = {2022}, abstract = {Background Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation. Methods The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19. Results Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95\% CI 1.019-30.867)) and ZnPP/L ratio (OR (74.313) (95\% CI 1.081-5108.103)). Conclusions For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.}, language = {en} } @phdthesis{Friedrich2010, author = {Friedrich, Maika}, title = {Wirkung von Teecatechin Epigallocatechingallat auf den Energiestoffwechsel der Maus}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-48159}, school = {Universit{\"a}t Potsdam}, year = {2010}, abstract = {Die gesundheitsf{\"o}rdernden Eigenschaften von gr{\"u}nem Tee sind weitgehend akzeptiert. Den Teecatechinen, insbesondere dem Epigallocatechin-3-gallat (EGCG), werden zahlreiche positive Effekte zugesprochen (z. B. antioxidativ, antikanzerogen, antiinflammatorisch, Blutdruck und Cholesterinspiegel senkend). Die Mechanismen, die zu einer Reduktion der in Tierversuchen beschriebenen K{\"o}rper- und Fettmasse f{\"u}hren, sind nicht ausreichend gekl{\"a}rt. Ziel dieser Arbeit bestand darin, die kurz- und mittelfristigen Wirkungen einer TEAVIGO®-Applikation (mind. 94 \% EGCG) am Mausmodell im Hinblick auf den Energie- und Fettstoffwechsel sowie die Expression daran beteiligter Gene in wichtigen Organen und Geweben zu untersuchen. In verschiedenen Tierversuchen wurde m{\"a}nnlichen C57BL/6-M{\"a}usen eine Hochfettdi{\"a}t (HFD) mit und ohne Supplementation (oral, di{\"a}tetisch) des entkoffeinierten Gr{\"u}ntee-Extraktes TEAVIGO® in unterschiedlichen Dosierungen gef{\"u}ttert. Es wurden sowohl kurz- als auch mittelfristige Wirkungen des EGCG auf die Energiebilanz (u. a. indirekte Tierkalorimetrie) und K{\"o}rperzusammensetzung (NMR) sowie die exogene Substratoxidation (Stabilisotopentechnik: Atemtests, Inkorporation nat{\"u}rlicher 13C-angereicherter Triglyceride aus Maiskeim{\"o}l in diverse Organe/Gewebe) und Gen-expression (quantitative real-time PCR) untersucht. Die Applikationsform und ihre Dauer riefen unterschiedliche Wirkungen hervor. M{\"a}use mit di{\"a}tetischer Supplementation zeigten bereits nach kurzer Zeit eine verminderte K{\"o}rperfettmasse, die bei weiterer Verabreichung auch zu einer Reduktion der K{\"o}rpermasse f{\"u}hrte. Beide Applikationsformen resultieren, unabh{\"a}ngig von der Dauer der Intervention, in einer erh{\"o}hten Energieausscheidung, w{\"a}hrend die Futter- und Energieaufnahme durch EGCG nicht beeinflusst wurden. Der Energieverlust war von einer erh{\"o}hten Fett- und Stickstoffausscheidung begleitet, deren Ursache die in der Literatur beschriebene Interaktion und Hemmung digestiver Enzyme sein k{\"o}nnte. Besonders unter postprandialen Bedingungen wiesen EGCG-M{\"a}use erniedrigte Triglycerid- und Glycogengehalte in der Leber auf, was auf eine eingeschr{\"a}nkte intestinale Absorption der N{\"a}hrstoffe hindeutet. Transkriptanalysen ergaben im Darm eine verminderte Expression von Fetts{\"a}uretransportern, w{\"a}hrend die Expression von Glucosetransportern durch EGCG erh{\"o}ht wurde. Weiterhin reduzierte EGCG, nach Umstellung von Standard- auf eine maiskeim{\"o}lhaltige Hochfettdi{\"a}t, die Inkorporation nat{\"u}rlicher 13C-angereicherter Triglyceride in diverse Organe und Gewebe - insbesondere Leber, viszerales und braunes Fettgewebe sowie Skelettmuskel. Die Analyse der 13C-Anreicherung im Atem der M{\"a}use und die Energieumsatzmessungen ergaben nach kurzer Applikation eine erh{\"o}hte Fettoxidation, die im weiteren Verlauf der Intervention auf eine erh{\"o}hte Kohlenhydratoxidation umgeschaltet wurde. Weiterhin war die orale Applikation von EGCG bei gleichzeitiger F{\"u}tterung einer Hochfettdi{\"a}t von makroskopischen und mikroskopischen degenerativen Ver{\"a}nderungen der Leber begleitet. Diese Effekte wurden nach di{\"a}tetischer Supplementation der Hochfettdi{\"a}t mit EGCG nicht beobachtet. Zusammenfassend zeigen die Ergebnisse, dass die K{\"o}rpergewichts- und Fettgewebs-abnahme durch di{\"a}tetisches EGCG sich durch eine herabgesetzte Verdaulichkeit der Nahrung erkl{\"a}ren l{\"a}sst. Dies f{\"u}hrte zu verschiedenen kurz- und mittelfristigen Ver{\"a}nderungen in der Fettverteilung und im Fettmetabolismus.}, language = {de} } @article{SieversRawelRingeletal.2016, author = {Sievers, Steven and Rawel, Harshadrai Manilal and Ringel, Karl Peter and Niggemann, Bodo and Beyer, Kirsten}, title = {Wheat protein recognition pattern in tolerant and allergic children}, series = {Pediatric Allergy and Immunology}, volume = {27}, journal = {Pediatric Allergy and Immunology}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0905-6157}, doi = {10.1111/pai.12502}, pages = {147 -- 155}, year = {2016}, abstract = {BackgroundWheat is one of the most common food allergens in early childhood. In contrast to other food allergies, wheat-specific IgE correlates badly with clinical symptoms and relevant components have been identified mostly for wheat-depended exercise-induced anaphylaxis. Moreover, a high percentage of patients present with immediate type symptoms but wheat-specific IgE cannot be detected with commercial available systems. ObjectiveWe addressed the question whether the IgE recognition pattern between wheat allergic (WA) and clinically tolerant (WT) children differs in order to identify individual proteins useful for component-resolved diagnostics. MethodsSera of 106 children with suspected wheat allergy, of whom 44 children had clinical relevant wheat allergy and 62 were tolerant upon oral food challenge, were analyzed for wheat-specific IgE using the ImmunoCap system as well as immunoblots against water and salt soluble, and water-insoluble protein fractions. 40 randomly selected sera were analyzed for specific IgE to 5-gliadin. ResultsSixty-three percent of the WT and 86\% of the WA children were sensitized to wheat with >0.35 kU(A)/l in ImmunoCAP analysis. We could confirm the role of -, ss-, -, and -gliadins, and LMW glutenin subunits as major allergens and found also IgE binding to a broad spectrum of water- and salt-soluble protein bands. It is of great importance that wheat allergic and tolerant patients showed IgE binding to the same protein bands. WT and WA did not significantly differ in levels of 5-gliadin-specific IgE. Conclusions \& Clinical RelevanceChildren with challenge proven clinical relevant food allergy and tolerant ones had a similar spectrum of IgE binding to the same protein bands. These findings imply that component-resolved diagnostics might not be helpful in the diagnostic work-up of wheat allergy.}, language = {en} } @phdthesis{FigueroaCampos2022, author = {Figueroa Campos, Gustavo Adolfo}, title = {Wet-coffee processing production wastes}, doi = {10.25932/publishup-55882}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-558828}, school = {Universit{\"a}t Potsdam}, pages = {X, 159}, year = {2022}, abstract = {Countries processing raw coffee beans are burdened with low economical incomes to fight the serious environmental problems caused by the by-products and wastewater that is generated during the wet-coffee processing. The aim of this work was to develop alternative methods of improving the waste by-product quality and thus making the process economically more attractive with valorization options that can be brought to the coffee producers. The type of processing influences not only the constitution of green coffee but also of by-products and wastewater. Therefore, coffee bean samples as well as by-products and wastewater collected at different production steps of were analyzed. Results show that the composition of wastewater is dependent on how much and how often the wastewater is recycled in the processing. Considering the coffee beans, results indicate that the proteins might be affected during processing and a positive effect of the fermentation on the solubility and accessibility of proteins seems to be probable. The steps of coffee processing influence the different constituents of green coffee beans which, during roasting, give rise to aroma compounds and express the characteristics of roasted coffee beans. Knowing that this group of compounds is involved in the Maillard reaction during roasting, this possibility could be utilized for the coffee producers to improve the quality of green coffee beans and finally the coffee cup quality. The valorization of coffee wastes through modification to activated carbon has been considered as a low-cost option creating an adsorbent with prospective to compete with commercial carbons. Activation protocol using spent coffee and parchment was developed and prepared to assess their adsorption capacity for organic compounds. Spent coffee grounds and parchment proved to have similar adsorption efficiency to commercial activated carbon. The results of this study document a significant information originating from the processing of the de-pulped to green coffee beans. Furthermore, it showed that coffee parchment and spent coffee grounds can be valorized as low-cost option to produce activated carbons. Further work needs to be directed to the optimization of the activation methods to improve the quality of the materials produced and the viability of applying such experiments in-situ to bring the coffee producer further valorization opportunities with environmental perspectives. Coffee producers would profit in establishing appropriate simple technologies to improve green coffee quality, re-use coffee by-products, and wastewater valorization.}, language = {en} } @phdthesis{Festag2004, author = {Festag, Matthias}, title = {Weiterentwicklung eines in vitro Embryotoxizit{\"a}tsassays : die Inhibierung der Differenzierung von murinen embryonalen Stammzellen zu Endothelzellen}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0001815}, school = {Universit{\"a}t Potsdam}, year = {2004}, abstract = {Substanzen der pharmazeutischen und chemischen Industrie m{\"u}ssen nach internationalen Richtlinien auf deren Toxizit{\"a}t gegen{\"u}ber Mensch und Umwelt gepr{\"u}ft werden. Dazu geh{\"o}ren u. a. Pr{\"u}fungen zur Vorhersage des embryotoxischen Potentials, die am lebenden Organismus durchgef{\"u}hrt werden. Mit dem Ziel die Anzahl der Tierversuche zu verringern, die notwendig sind um das toxikologische Profil einer Pr{\"u}fsubstanz zu bestimmen, wurde der Embryonale Stammzelltest (EST) entwickelt. Als Grundlage des EST dienen embryonale Stammzellen (ES-Zellen) einer Zelllinie. ES-Zellen sind Zellen, die sich in der fr{\"u}hen embryonalen Entwicklung in die Zellen der Keimbl{\"a}tter entwickeln k{\"o}nnen. Daraus wiederum differenzieren die vielen verschiedenen, unterschiedlich spezialisierten Zelltypen des komplexen Organismus. Im EST wird die Konzentration einer Pr{\"u}fsubstanz bestimmt, bei der die Differenzierung von ES-Zellen zu Herzmuskelzellen zu 50 \% inhibiert wird. Zus{\"a}tzlich wird die Konzentration der Pr{\"u}fsubstanz bestimm\&\#176;t, bei der 50 \% der ES-Zellen (IC50D3) bzw. Fibroblastenzellen (IC503T3) absterben. Die allgemeine Toxizit{\"a}t ist damit von der spezifischen Toxizit{\"a}t der Pr{\"u}fsubstanz auf die ES-Zellen und deren Differenzierung unterscheidbar. Die Parameter fliessen in ein biostatistisches Modell zur Pr{\"a}diktion des embryotoxischen Potentials der Pr{\"u}fsubstanzen ein. Es wurde ein Versuchsprotokoll entwickelt, wonach die ES-Zellen sich verst{\"a}rkt zu Endothelzellen differenzieren. Die Endothelzellen, die im lebenden Organismus die Wand der sp{\"a}teren Blutgef{\"a}sse, wie Venen und Arterien bilden, wurden mittels molekularbiologischer Methoden auf der RNA- und der Protein-Ebene nachgewiesen und quantifiziert. Verschiedene Zellkulturmethoden, Wachstumsfaktoren, als auch Wachstumsfaktorkonzentrationen wurden auf deren Verm{\"o}gen die Differenzierung der ES-Zellen zu Endothelzellen zu induzieren, untersucht. Nach der Etablierung des Differenzierungsprotokolls wurden sieben Substanzen auf deren Verm{\"o}gen gepr{\"u}ft, die Differenzierung von ES-Zellen zu Endothelzellen zu inhibieren. Die Endothelzellen wurden dabei {\"u}ber die Expression der RNA von zwei endothelzellspezifischen Genen quantifiziert. Im Vergleich dazu wurden die IC50D3 und die IC503T3 der Pr{\"u}fsubstanz bestimmt, um eine Absch{\"a}tzung des embryotoxischen Potentials der Pr{\"u}fsubstanz zu erm{\"o}glichen. Die Ergebnisse zeigten, dass eine Absch{\"a}tzung des embryotoxischen Potentials der sieben Pr{\"u}fsubstanzen in nicht-, schwach- oder stark embryotoxisch vorgenommen werden konnte. Es ist zu schlussfolgern, dass der weiterentwickelte in vitro Embryotoxizit{\"a}tsassay sensitiv und reproduzierbar ist. Mit der Verwendung von verschiedenen Differenzierungsendpunkten kann die Pr{\"a}diktionskraft des Assays deutlich verbessert, und die Anzahl von Tierversuchen verringert werden. Durch die Verwendung von molekularbiologischen Markern kann der Assay einem Hochdurchsatzscreening zug{\"a}ngig gemacht werden und damit die Anzahl von Pr{\"u}fsubstanzen deutlich erh{\"o}ht werden.}, language = {de} } @misc{ChristakoudiPagoniFerrarietal.2020, author = {Christakoudi, Sofia and Pagoni, Panagiota and Ferrari, Pietro and Cross, Amanda J. and Tzoulaki, Ioanna and Muller, David C. and Weiderpass, Elisabete and Freisling, Heinz and Murphy, Neil and Dossus, Laure and Turzanski Fortner, Renee and Agudo, Antonio and Overvad, Kim and Perez-Cornago, Aurora and Key, Timothy J. and Brennan, Paul and Johansson, Mattias and Tjonneland, Anne and Halkjaer, Jytte and Boutron-Ruault, Marie-Christine and Artaud, Fanny and Severi, Gianluca and Kaaks, Rudolf and Schulze, Matthias Bernd and Bergmann, Manuela M. and Masala, Giovanna and Grioni, Sara and Simeon, Vittorio and Tumino, Rosario and Sacerdote, Carlotta and Skeie, Guri and Rylander, Charlotta and Borch, Kristin Benjaminsen and Quiros, J. Ramon and Rodriguez-Barranco, Miguel and Chirlaque, Maria-Dolores and Ardanaz, Eva and Amiano, Pilar and Drake, Isabel and Stocks, Tanja and Haggstrom, Christel and Harlid, Sophia and Ellingjord-Dale, Merete and Riboli, Elio and Tsilidis, Konstantinos K.}, title = {Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {7}, issn = {1866-8372}, doi = {10.25932/publishup-57360}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-573609}, pages = {17}, year = {2020}, abstract = {Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31\% men), 20\% lost and 32\% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95\% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.}, language = {en} } @article{ChristakoudiPagoniFerrarietal.2020, author = {Christakoudi, Sofia and Pagoni, Panagiota and Ferrari, Pietro and Cross, Amanda J. and Tzoulaki, Ioanna and Muller, David C. and Weiderpass, Elisabete and Freisling, Heinz and Murphy, Neil and Dossus, Laure and Turzanski Fortner, Renee and Agudo, Antonio and Overvad, Kim and Perez-Cornago, Aurora and Key, Timothy J. and Brennan, Paul and Johansson, Mattias and Tjonneland, Anne and Halkjaer, Jytte and Boutron-Ruault, Marie-Christine and Artaud, Fanny and Severi, Gianluca and Kaaks, Rudolf and Schulze, Matthias Bernd and Bergmann, Manuela M. and Masala, Giovanna and Grioni, Sara and Simeon, Vittorio and Tumino, Rosario and Sacerdote, Carlotta and Skeie, Guri and Rylander, Charlotta and Borch, Kristin Benjaminsen and Quiros, J. Ramon and Rodriguez-Barranco, Miguel and Chirlaque, Maria-Dolores and Ardanaz, Eva and Amiano, Pilar and Drake, Isabel and Stocks, Tanja and H{\"a}ggstr{\"o}m, Christel and Harlid, Sophia and Ellingjord-Dale, Merete and Riboli, Elio and Tsilidis, Konstantinos K.}, title = {Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort}, series = {International journal of cancer}, volume = {148}, journal = {International journal of cancer}, number = {7}, publisher = {Wiley}, address = {Hoboken}, issn = {0020-7136}, doi = {10.1002/ijc.33339}, pages = {1637 -- 1651}, year = {2020}, abstract = {Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31\% men), 20\% lost and 32\% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95\% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.}, language = {en} } @phdthesis{Kluth2006, author = {Kluth, Dirk}, title = {Vom Antioxidanz zum Genregulator : transkriptionelle Regulation von Phase I- und Phase II-Enzymen durch Vitamin E und antioxidative sekund{\"a}re Pflanzeninhaltsstoffe}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-10060}, school = {Universit{\"a}t Potsdam}, year = {2006}, abstract = {Nahrungsinhaltsstoffe sind im Organismus an Steuerungsprozessen und Stoffwechselvorg{\"a}ngen beteiligt, wobei die Mechanismen ihrer Wirkung noch nicht v{\"o}llig aufgekl{\"a}rt sind. Wie Vitamin E zeigen auch sekund{\"a}re Pflanzeninhaltsstoffe in Zellsystemen sowie in vivo eine Reihe biologischer Wirkungen, deren Erkl{\"a}rung jedoch h{\"a}ufig auf ihre antioxidative Eigenschaft reduziert wird. Ziel der Dissertation war es, den Einfluss von Vitamin E und anderen Pflanzeninhaltsstoffen (in Form von Pflanzenextrakten oder isolierten sekund{\"a}ren Pflanzeninhaltsstoffen, z.B. Polyphenole), die bisher alle haupts{\"a}chlich als Antioxidanz klassifiziert wurden, auf die transkriptionelle Regulation von Phase I- und Phase II-Enzymen zu untersuchen. Dazu wurde die Aktivierung des PXR (pregnane X receptor) und des Nrf2 (NF-E2-related factor-2) als zentrale Transkriptionsfaktoren der Phase I- bzw. Phase II-Enzyme getestet. Der Einfluss von verschiedenen Vitamin E-Formen und antioxidativen Pflanzeninhaltsstoffen in Form von Reinsubstanzen (Curcumin, EGCG, Medox, Quercetin, Resveratrol und Sulforaphan) oder Pflanzenextrakten (aus Blaubeeren, Gew{\"u}rznelken, Himbeeren, Nelkenpfeffer, Thymian oder Waln{\"u}ssen) auf die Aktivierung von PXR und Nrf2 sowie des Promotors eines jeweiligen Zielgens (CYP3A4 bzw. GI-GPx) wurde in vitro mit Reportergenplasmiden untersucht. Es zeigte sich, dass sowohl Vitamin E-Formen als auch verschiedene sekund{\"a}re Pflanzeninhaltsstoffe PXR und/oder Nrf2 sowie die Promotoren der jeweiligen Zielgene CYP3A4 bzw. GI-GPx aktivieren. In einem Tierexperiment konnte diese genregulatorische Wirkung von Vitamin E auf die in vivo-Situation {\"u}bertragen werden. In Lebern von M{\"a}usen, deren Futter unterschiedliche Mengen von Vitamin E enthielt (Mangel-, Normal- und {\"U}berflussdi{\"a}t), wurde eine direkte Korrelation zwischen der alpha-Tocopherol-Konzentration und der Cyp3a11 mRNA-Expression nachgewiesen (Cyp3a11 ist das murine Homolog zum humanen CYP3A4). Entgegen der in vitro-Situation hatte gamma-Tocotrienol in vivo einen nur kaum nachweisbaren Effekt auf die Expression der Cyp3a11 mRNA, induzierte aber die Expression der alpha-TTP mRNA. Es konnte gezeigt werden, dass Vitamin E und sekund{\"a}re Pflanzeninhaltsstoffe Phase I- und Phase II-Enzyme transkriptionell regulieren k{\"o}nnen. Die Wirkungen des Vitamin E k{\"o}nnen sich allerdings nur entfalten, wenn die Vitamin E-Formen ausreichend vom K{\"o}rper aufgenommen werden. Gegenstand der Dissertation waren daher auch Untersuchungen zur Bioverf{\"u}gbarkeit (zellul{\"a}re Akkumulation und Metabolismus) verschiedener Vitamin E-Formen. Es konnte gezeigt werden, dass Unterschiede in der chemischen Struktur der Vitamin E-Formen deren zellul{\"a}re Akkumulation und Metabolisierung beeinflussen. Unter Ber{\"u}cksichtigung der Ergebnisse der Dissertation lassen sich protektive Wirkungen von antioxidativen Nahrungsinhaltsstoffen auch unabh{\"a}ngig von ihren antioxidativen Eigenschaften {\"u}ber die Induktion zelleigener Schutzsysteme, einschließlich der Phase I- und Phase II-Enzyme, erkl{\"a}ren. Die Induktion der zelleigenen Abwehr l{\"a}sst sich auch als adaptive Antwort (sog. "adaptive response") des Organismus gegen{\"u}ber zellsch{\"a}digenden Ereignissen betrachten.}, subject = {Vitamin E}, language = {de} } @article{Schweigert2000, author = {Schweigert, Florian J.}, title = {Vitamine}, year = {2000}, language = {de} } @article{CarlsohnScharhagRosenbergerHeydenreichetal.2013, author = {Carlsohn, Anja and Scharhag-Rosenberger, Friederike and Heydenreich, Juliane and Mayer, Frank}, title = {Vitamin-D-Status of athletes with higher UV-exposure during training}, series = {Ern{\"a}hrungs-Umschau : Forschung \& Praxis}, volume = {60}, journal = {Ern{\"a}hrungs-Umschau : Forschung \& Praxis}, number = {10}, publisher = {Umschau-Zeitschriftenverl.}, address = {Frankfurt, Main}, issn = {0174-0008}, pages = {174 -- 176}, year = {2013}, language = {de} } @phdthesis{Nell2009, author = {Nell, Sandra}, title = {Vitamin E und der vesikul{\"a}re Transport : Untersuchungen zu den genregulatorischen Funktionen von Vitamin E mittels Microarray- und real time PCR-Analysen in der Maus und funktionellen in vitro Assays in RBL-2H3 Zellen}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-35710}, school = {Universit{\"a}t Potsdam}, year = {2009}, abstract = {Vitamin E wird immer noch als das wichtigste lipophile Antioxidanz in biologischen Membranen betrachtet. In den letzten Jahren hat sich jedoch der Schwerpunkt der Vitamin E-Forschung hin zu den nicht-antioxidativen Funktionen verlagert. Besonderes Interesse gilt dabei dem α-Tocopherol, der h{\"a}ufigsten Vitamin E-Form im Gewebe von S{\"a}ugetieren, und seiner Rolle bei der Regulation der Genexpression. Das Ziel dieser Dissertation war die Untersuchung der genregulatorischen Funktionen von α-Tocoperol und die Identifizierung α-Tocopherol-sensitiver Gene in vivo. Zu diesem Zweck wurden M{\"a}use mit verschiedenen Mengen α-Tocopherol gef{\"u}ttert. Die Analyse der hepatischen Genexpression mit Hilfe von DNA-Microarrays identifizierte 387 α-Tocopherol-sensitive Gene. Funktionelle Clusteranalysen der differentiell exprimierten Gene zeigten einen Einfluss von α-Tocooherol auf zellul{\"a}re Transportprozesse. Besonders solche Gene, die an vesikul{\"a}ren Transportvorg{\"a}ngen beteiligt sind, wurden gr{\"o}ßtenteils durch α-Tocopherol hochreguliert. F{\"u}r Syntaxin 1C, Vesicle-associated membrane protein 1, N-ethylmaleimide-sensitive factor and Syntaxin binding protein 1 konnte eine erh{\"o}hte Expression mittels real time PCR best{\"a}tigt werden. Ein funktioneller Einfluss von α-Tocopherol auf vesikul{\"a}re Transportprozesse konnte mit Hilfe des in vitro β-Hexosaminidase Assays in der sekretorischen Mastzelllinie RBL-2H3 gezeigt werden. Die Inkubation der Zellen mit α-Tocopherol resultierte in einer konzentrationsabh{\"a}ngigen Erh{\"o}hung der PMA/Ionomycin-stimulierten Sekretion der β-Hexosaminidase. Eine erh{\"o}hte Expression ausgew{\"a}hlter Gene, die an der Degranulation beteiligt sind, konnte nicht beobachtet werden. Damit schien ein direkter genregulatorischer Effekt von α-Tocopherol eher unwahrscheinlich. Da eine erh{\"o}hte Sekretion auch mit β-Tocopherol aber nicht mit Trolox, einem hydrophilen Vitamin E-Analogon, gefunden wurde, wurde vermutet, dass α-Tocopherol die Degranulation m{\"o}glicherweise durch seine membranst{\"a}ndige Lokalisation beeinflussen k{\"o}nnte. Die Inkubation der Zellen mit α-Tocopherol resultierte in einer ver{\"a}nderten Verteilung des Gangliosids GM1, einem Lipid raft Marker. Es wird angenommen, dass diese Membranmikrodom{\"a}nen als Plattformen f{\"u}r Signaltransduktionsvorg{\"a}nge fungieren. Ein m{\"o}glicher Einfluss von Vitamin E auf die Rekrutierung/Translokation von Signalproteinen in Membranmikrodom{\"a}nen k{\"o}nnte die beobachteten Effekte erkl{\"a}ren. Eine Rolle von α-Tocopherol im vesikul{\"a}ren Transport k{\"o}nnte nicht nur seine eigene Absorption und seinen Transport beeinflussen, sondern auch eine Erkl{\"a}rung f{\"u}r die bei schwerer Vitamin E-Defizienz auftretenden neuronalen Dysfunktionen bieten. Im zweiten Teil der Arbeit wurde die α-Tocopheroltransferprotein (Ttpa) Knockout-Maus als genetisches Modell f{\"u}r Vitamin E-Defizienz verwendet, um den Effekt von Ttpa auf die Genexpression und die Gewebeverteilung von α-Tocopherol zu analysieren. Ttpa ist ein cytosolisches Protein, das f{\"u}r die selektive Retention von α-Tocopherol in der Leber verantwortlich ist. Die Ttpa-Defizienz resultierte in sehr geringen α-Tocopherol-Konzentrationen im Plasma und den extrahepatischen Geweben. Die Analyse der α-Tocopherol-Gehalte im Gehirn wies auf eine Rolle von Ttpa bei der α-Tocopherol-Aufnahme ins Gehirn hin.}, language = {de} } @phdthesis{Landes2005, author = {Landes, Nico}, title = {Vitamin E : elucidation of the mechanism of side chain degradation and gene regulatory functions}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-5222}, school = {Universit{\"a}t Potsdam}, year = {2005}, abstract = {For more than 80 years vitamin E has been in the focus of scientific research. Most of the progress concerning non-antioxidant functions, nevertheless, has only arisen from publications during the last decade. Most recently, the metabolic pathway of vitamin E has been almost completely elucidated. Vitamin E is metabolized by truncation of its side chain. The initial step of an omega-hydroxylation is carried out by cytochromes P450 (CYPs). This was evidenced by the inhibition of the metabolism of alpha-tocopherol by ketoconozole, an inhibitor of CYP3A expression, whereas rifampicin, an inducer of CYP3A expression increased the metabolism of alpha-tocopherol. Although the degradation pathway is identical for all tocopherols and tocotrienols, there is a marked difference in the amount of the release of metabolites from the individual vitamin E forms in cell culture as well as in experimental animals and in humans. Recent findings not only proposed an CYP3A4-mediated degradation of vitamin E but also suggested an induction of the metabolizing enzymes by vitamin E itself. In order to investigate how vitamin E is able to influence the expression of metabolizing enzymes like CYP3A4, a pregnane X receptor (PXR)-based reporter gene assay was chosen. PXR is a nuclear receptor which regulates the transcription of genes, e.g., CYP3A4, by binding to specific DNA response elements. And indeed, as shown here, vitamin E is able to influence the expression of CYP3A via PXR in an in vitro reporter gene assay. Tocotrienols showed the highest activity followed by delta- and alpha-tocopherol. An up-regulation of Cyp3a11 mRNA, the murine homolog of the human CYP3A4, could also be confirmed in an animal experiment. The PXR-mediated change in gene expression displayed the first evidence of a direct transcriptional activity of vitamin E. PXR regulates the expression of genes involved in xenobiotic detoxification, including oxidation, conjugation, and transport. CYP3A, e.g., is involved in the oxidative metabolism of numerous currently used drugs. This opens a discussion of possible side effects of vitamin E, but the extent to which supranutritional doses of vitamin E modulate these pathways in humans has yet to be determined. Additionally, as there is arising evidence that vitamin E's essentiality is more likely to be based on gene regulation than on antioxidant functions, it appeared necessary to further investigate the ability of vitamin E to influence gene expression. Mice were divided in three groups with diets (i) deficient in alpha-tocopherol, (ii) adequate in alpha-tocopherol supply and (iii) with a supranutritional dosage of alpha-tocopherol. After three months, half of each group was supplemented via a gastric tube with a supranutritional dosage of gamma-tocotrienol per day for 7 days. Livers were analyzed for vitamin E content and liver RNA was prepared for hybridization using cDNA array and oligonucleotide array technology. A significant change in gene expression was observed by alpha-tocopherol but not by gamma-tocotrienol and only using the oligonucleotide array but not using the cDNA array. The latter effect is most probably due to the limited number of genes represented on a cDNA array, the lacking gamma-tocotrienol effect is obviously caused by a rapid degradation, which might prevent bioefficacy of gamma-tocotrienol. Alpha-tocopherol changed the expression of various genes. The most striking observation was an up-regulation of genes, which code for proteins involved in synaptic transmitter release and calcium signal transduction. Synapsin, synaptotagmin, synaptophysin, synaptobrevin, RAB3A, complexin 1, Snap25, ionotropic glutamate receptors (alpha 2 and zeta 1) were shown to be up-regulated in the supranutritional group compared to the deficient group. The up-regulation of synaptic genes shown in this work are not only supported by the strong concentration of genes which all are involved in the process of vesicular transport of neurotransmitters, but were also confirmed by a recent publication. However, a confirmation by real time PCR in neuronal tissue like brain is now required to explain the effect of vitamin E on neurological functionality. The change in expression of genes coding for synaptic proteins by vitamin E is of principal interest thus far, since the only human disease directly originating from an inadequate vitamin E status is ataxia with isolated vitamin E deficiency. Therefore, with the results of this work, an explanation for the observed neurological symptoms associated with vitamin E deficiency can be presented for the first time.}, subject = {Vitamin E}, language = {en} } @article{KaruwanarintPhonratTungtrongchitretal.2018, author = {Karuwanarint, Piyaporn and Phonrat, Benjaluck and Tungtrongchitr, Anchalee and Suriyaprom, Kanjana and Chuengsamarn, Somlak and Schweigert, Florian J. and Tungtrongchitr, Rungsunn}, title = {Vitamin D-binding protein and its polymorphisms as a predictor for metabolic syndrome}, series = {Biomarkers in medicine}, volume = {12}, journal = {Biomarkers in medicine}, number = {5}, publisher = {Future Medicine}, address = {London}, issn = {1752-0363}, doi = {10.2217/bmm-2018-0029}, pages = {465 -- 473}, year = {2018}, abstract = {Aim: To investigate the relationship of vitamin D-binding protein (GC) and genetic variation of GC (rs4588, rs7041 and rs2282679) with metabolic syndrome (MetS) in the Thai population. Materials \& methods: GCglobulin concentrations were measured by quantitative western blot analysis in 401 adults. All participants were genotyped using TaqMan allelic discrimination assays. Results: GC-globulin levels were significatly lower in MetS subjects than in control subjects, in which significant negative correlations of GC-globulin levels with systolic blood pressure, glucose and age were found. Male participants who carried the GT genotype for rs4588 showed an increased risk of MetS compared with the GG wild-type (odds ratio: 3.25; p = 0.004). Conclusion: GC-globulin concentrations and variation in GC rs4588 were supported as a risk factor for MetS in Thais.}, language = {en} }