TY - JOUR A1 - Epp, Laura Saskia A1 - Stoof-Leichsenring, Kathleen Rosemarie A1 - Trauth, Martin H. A1 - Tiedemann, Ralph T1 - Molecular profiling of diatom assemblages in tropical lake sediments using taxon-specific PCR and Denaturing High-Performance Liquid Chromatography (PCR-DHPLC) JF - Molecular ecology resources N2 - Here we present a protocol to genetically detect diatoms in sediments of the Kenyan tropical Lake Naivasha, based on taxon-specific PCR amplification of short fragments (approximately 100 bp) of the small subunit ribosomal (SSU) gene and subsequent separation of species-specific PCR products by PCR-based denaturing high-performance liquid chromatography (DHPLC). An evaluation of amplicons differing in primer specificity to diatoms and length of the fragments amplified demonstrated that the number of different diatom sequence types detected after cloning of the PCR products critically depended on the specificity of the primers to diatoms and the length of the amplified fragments whereby shorter fragments yielded more species of diatoms. The DHPLC was able to discriminate between very short amplicons based on the sequence difference, even if the fragments were of identical length and if the amplicons differed only in a small number of nucleotides. Generally, the method identified the dominant sequence types from mixed amplifications. A comparison with microscopic analysis of the sediment samples revealed that the sequence types identified in the molecular assessment corresponded well with the most dominant species. In summary, the PCR-based DHPLC protocol offers a fast, reliable and cost-efficient possibility to study DNA from sediments and other environmental samples with unknown organismic content, even for very short DNA fragments. KW - diatoms KW - environmental DNA KW - lake sediments KW - PCR-DHPLC Y1 - 2011 U6 - https://doi.org/10.1111/j.1755-0998.2011.03022.x SN - 1755-098X VL - 11 IS - 5 SP - 842 EP - 853 PB - Wiley-Blackwell CY - Hoboken ER - TY - THES A1 - Schatz, Daniela T1 - LNA-clamp-PCR zum sensitiven Nachweis von Punktmutationen im Rahmen der Entwicklung eines Darmkrebsfrüherkennungstests T1 - LNA-clamp-PCR as a method for sensitive detection of point mutations as part of the development of an assay for the early diagnosis of colon cancer N2 - Darmkrebs ist die zweithäufigste malignombedingte Todesursache in den westlichen Industrieländern. Durch eine frühzeitige Diagnose besteht jedoch eine hohe Chance auf Heilung. Der Goldstandard zur Darmkrebsfrüherkennung ist gegenwärtig die Koloskopie. Eine Darmspiegelung ist jedoch invasiv und mit Unannehmlichkeiten für den Patienten verbunden. Die Akzeptanz in der Bevölkerung ist daher gering. Ziel des BMBF- Projektes „Entwicklung eines nichtinvasiven Nachweissystems zur Früherkennung von humanem Darmkrebs“, in dessen Rahmen diese Arbeit entstand, ist die Bereitstellung eines nichtinvasiven Nachweisverfahrens zur Darmkrebsfrüherkennung. Der Nachweis soll über die Detektion von aus neoplastischen Zellen stammender DNA in Stuhl erfolgen. Die Entartung dieser Zellen beruht auf Veränderungen im Erbgut, welches unter anderem Mutationen sind. Im ersten Teil des BMBF-Projektes wurde ein Set von Mutationen zusammengestellt, welches eine hohe Sensitivität für Vorstufen von Darmkrebs aufweist. Ziel dieser Arbeit war es, eine Nachweismethode für die zuvor identifizierten Punktmutationen zu entwickeln. Das Nachweisverfahren musste dabei unempfindlich gegen einen hohen Hintergrund nichtmutierter DNA sein, da im Stuhl geringe Mengen DNA aus neoplastischen Zellen bei einem hohen Hintergrund von DNA aus gesunden Zellen vorliegen. Hierzu wurden Plasmidmodellsysteme für die aus dem Marker-Set stammenden Genfragmente BRAF und dessen Mutante V600E, CTNNB1 und T41I, T41A, S45P und K-ras G12C hergestellt. Mit Hilfe dieser Plasmidmodellsysteme wurde dann das Nachweissystem entwickelt. Der entscheidende Schritt für die Detektion von Punktmutationen bei hohem Wildtypüberschuss ist eine vorhergehende Anreicherung. In der vorliegenden Arbeit wurde dazu die Methode der LNA-clamp-PCR (locked nucleic acid) etabliert. Die Bewertung der erzielten Anreicherung erfolgte über das relative Detektionslimit. Zur Bestimmung des Detektionslimits wurde die Schmelzkurvenanalyse von Hybridisierungssonden eingesetzt; diese wurde im Rahmen dieser Arbeit für die drei oben genannten Genfragmente und ihre Mutanten entwickelt. Die LNA-clamp-PCR wird in Anwesenheit eines LNA-Blockers durchgeführt. Das Nukleotidanalogon LNA weist im Vergleich zu DNA eine erhöhte Affinität zu komplementären DNA-Strängen auf. Gleichzeitig kommt es bei Anwesenheit einer Basenfehlpaarung zu einer größeren Destabilisierung der Bindung. Als Blocker werden kurze LNA-DNA-Hybridoligonukleotide eingesetzt, die den mutierten Sequenzbereich überspannen und selbst der Wildtypsequenz entsprechen. Durch Bindung an die Wildtypsequenz wird deren Amplifikation während der PCR verhindert (clamp = arretieren, festklemmen). Der Blocker selbst wird dabei nicht verlängert. Der Blocker bindet unter optimalen Bedingungen jedoch nicht an die mutierte Sequenz. Die Mutante wird daher ungehindert amplifiziert und somit gegenüber dem Wildtyp-Fragment angereichert. Die Position des Blockers kann im Bindungsbereich eines der Primer sein und hier dessen Hybridisierung an dem Wildtyp-Fragment verhindern oder zwischen den beiden Primern liegen und so die Synthese durch die Polymerase inhibieren. Die Anwendbarkeit beider Systeme wurde in dieser Arbeit gezeigt. Die LNA-clamp-PCR mit Primerblocker wurde für BRAF etabliert. Es wurde ein Detektionslimit von mindestens 1:100 erzielt. Die LNA-clamp-PCR mit Amplifikationsblocker wurde erfolgreich für BRAF, K-ras und CTNNB1: T41I, T41A mit einem Detektionslimit von 1:1000 bis 1:10 000 entwickelt. In Stuhlproben liegt DNA aus neoplastischen Zellen nach Literaturangaben zu einem Anteil von 1% bis 0,1% vor. Die LNA-clamp-PCR weist also mit Amplifikationsblockern ein ausreichend hohes Detektionslimit für die Analyse von Stuhlproben auf. Durch die erfolgreiche Etablierung der Methode auf drei verschiedenen Genfragmenten und vier unterschiedlichen Punktmutationen konnte deren universelle Einsetzbarkeit gezeigt werden. Für die Ausweitung der LNA-clamp-PCR auf die übrigen Mutationen des Marker-Sets wurden Richtlinien ausgearbeitet und die Blockereffizienz als Kennzahl eingeführt. Die LNA-clamp-PCR ist ein schnelles, kostengünstiges Verfahren, welches einen geringen Arbeitsaufwand erfordert und wenig fehleranfällig ist. Sie ist somit ein geeignetes Anreicherungsverfahren für Punktmutationen in einem diagnostischen System zur Darmkrebsfrüherkennung. Darüber hinaus kann die LNA-clamp-PCR auch in anderen Bereichen, in denen die Detektion von Punktmutationen in einem hohen Wildtyphintergrund erforderlich ist, eingesetzt werden. N2 - Colon cancer is the second leading cause of cancer related deaths in the western world. However if diagnosed early there is a great chance curing the disease. Coloscopy is the gold standard for early detection of colorectal cancer today. Its greatest disadvantage is the fact that it is an invasive technique and provides some discomfort for the patients. Therefore, the compliance to undergo such a procedure is extremely low. This work was generated in the context of the BMBF-project „Development of a non-invasive assay for the early detection of preneoplastic and neoplastic lesions in the human colon“. The aim of the work described here is the development of a non-invasive assay for the early detection of colon cancer. The assay should detect DNA from neoplastic cells in feces samples. The transformation of these cells is based on alterations in the genome predominantly mutations. In the first part of the BMBF-project a mutation panel with high sensitivity for preneoplastic lesions of colon cancer was determined. The aim of this work was to develop a detection method for the point mutations of the determined mutation panel. The rare mutant DNA needs to be detected in the presence of a great amount of wild-type DNA shed from healthy tissue. The assay system needs to be insensitive to this high background of healthy DNA. Therefore a model system of plasmid DNA containing gene fragments of BRAF and its mutation V600E, CTNNB1 and T41I, T41A, S45P and K-ras G12C obtained from the marker panel was established. Using these plasmid system the detection method was developed. The most critical parameter for the detection of rare point mutations is an enrichment of these rare DNA molecules. In this work LNA-clamp-PCR (locked nucleic acid) technology was used to enrich the mutant DNA.. For the estimation of the achieved enrichment the relative detection limit was used. The detection limit was determined by melting curve analysis of hybridization probes. These assays were established in the present work for the three above mentioned gene fragments. LNA-clamp-PCR is performed in the presence of an LNA blocker. LNA is a synthetic DNA analog. LNA nucleotide analog bind to complementary DNA strands with higher affinity. In addition a single mismatch in the LNA-DNA duplex causes a much greater destabilization compared to a DNA-DNA duplex. Short LNA-DNA-hybrids were used as clamp, which cover the mutated region and represent the wild-type sequence. Within an appropriate temperature range, LNA can specifically bind to wild type template and can inhibit its amplification. The clamp itself will not be elongated. Under optimal conditions the LNA clamp will not interfere with the amplification of the mismatched template. Therefore the mutated gene fragment will be enriched in comparison to the wild-type. The position of the LNA clamp can either be at the primer binding site inhibiting primer hybridization on the wild-type fragment or the LNA clamp is positioned between the two primer binding sites inhibiting chain elongation of the perfectly matched template. In the present work both systems were applied. For the gene fragment BRAF the LNA was used at the primer binding site. The achieved detection limit was at least 1:100. The LNA-clamp-PCR with LNA inhibiting the chain elongation were developed successfully for BRAF, K-ras and CTNNB1: T41I, T41A achieving a detection limit of 1:1000 to 1:10 000. According to the literature 1% to 0.1% of the DNA in feces derives from neoplastic cells. Therefore the detection limit achieved by LNA-clamp-PCR with LNA inhibiting chain elongation would be sufficient for analyzing feces samples. LNA-clamp-PCR protocols were established for three different gene fragments and four diverse point mutations indicating that the technology can generally be used for high sensitive detection of DNA mutations. For the development of LNA-clamp-PCR protocols for the other mutations of the marker panel development guidelines were established. Clamp efficiency was identified as a quantitative parameter for protocol optimization. The LNA-clamp-PCR is a robust, fast and cost-saving technique which needs low labor input. Therefore the method is adequate for enriching point mutated gene fragments in a diagnostic assay for the detection of early colon cancer stages. In addition LNA-clamp-PCR can be applied in other fields where rare sequence variations need to be detected in the presence of high wild-type DNA background. KW - LNA-clamp-PCR KW - Darmkrebsdiagnostik KW - Punktmutation KW - BRAF KW - K-ras KW - LNA- clamp-PCR KW - colon cancer diagnosis KW - point mutation KW - BRAF KW - K-ras Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-52308 ER - TY - THES A1 - Loßow, Kristina T1 - Erzeugung und Charakterisierung von Mausmodellen mit lichtsensitivem Geschmackssystem zur Aufklärung der neuronalen Geschmackskodierung T1 - Generation and characterization of transgenic lines of mice to elucidate neuralnetworks engaged in processing of gustatory information N2 - Die Wahrnehmung von Geschmacksempfindungen beruht auf dem Zusammenspiel verschiedener Sinneseindrücke wie Schmecken, Riechen und Tasten. Diese Komplexität der gustatorischen Wahrnehmung erschwert die Beantwortung der Frage wie Geschmacksinformationen vom Mund ins Gehirn weitergeleitet, prozessiert und kodiert werden. Die Analysen zur neuronalen Prozessierung von Geschmacksinformationen erfolgten zumeist mit Bitterstimuli am Mausmodell. Zwar ist bekannt, dass das Genom der Maus für 35 funktionelle Bitterrezeptoren kodiert, jedoch war nur für zwei unter ihnen ein Ligand ermittelt worden. Um eine bessere Grundlage für tierexperimentelle Arbeiten zu schaffen, wurden 16 der 35 Bitterrezeptoren der Maus heterolog in HEK293T-Zellen exprimiert und in Calcium-Imaging-Experimenten funktionell charakterisiert. Die Daten belegen, dass das Funktionsspektrum der Bitterrezeptoren der Maus im Vergleich zum Menschen enger ist und widerlegen damit die Aussage, dass humane und murine orthologe Rezeptoren durch das gleiche Ligandenspektrum angesprochen werden. Die Interpretation von tierexperimentellen Daten und die Übertragbarkeit auf den Menschen werden folglich nicht nur durch die Komplexität des Geschmacks, sondern auch durch Speziesunterschiede verkompliziert. Die Komplexität des Geschmacks beruht u. a. auf der Tatsache, dass Geschmacksstoffe selten isoliert auftreten und daher eine Vielzahl an Informationen kodiert werden muss. Um solche geschmacksstoffassoziierten Stimuli in der Analyse der gustatorischen Kommunikationsbahnen auszuschließen, sollten Opsine, die durch Licht spezifischer Wellenlänge angeregt werden können, für die selektive Ersetzung von Geschmacksrezeptoren genutzt werden. Um die Funktionalität dieser angestrebten Knockout-Knockin-Modelle zu evaluieren, die eine Kopplung von Opsinen mit dem geschmacksspezifischen G-Protein Gustducin voraussetzte, wurden Oozyten vom Krallenfrosch Xenopus laevis mit dem Zwei-Elektroden-Spannungsklemm-Verfahren hinsichtlich dieser Interaktion analysiert. Der positiven Bewertung dieser Kopplung folgte die Erzeugung von drei Mauslinien, die in der kodierenden Region eines spezifischen Geschmacksrezeptors (Tas1r1, Tas1r2, Tas2r114) Photorezeptoren exprimierten. Durch RT-PCR-, In-situ-Hybridisierungs- und immunhistochemische Experimente konnte der erfolgreiche Knockout der Rezeptorgene und der Knockin der Opsine belegt werden. Der Nachweis der Funktionalität der Opsine im gustatorischen System wird Gegenstand zukünftiger Analysen sein. Bei erfolgreichem Beleg der Lichtempfindlichkeit von Geschmacksrezeptorzellen dieser Mausmodelle wäre ein System geschaffen, dass es ermöglichen würde, gustatorische neuronale Netzwerke und Hirnareale zu identifizieren, die auf einen reinen geschmacks- und qualitätsspezifischen Stimulus zurückzuführen wären. N2 - Taste impression is based on the interaction of taste, smell and touch. To evaluate the nutritious content of food mammals possess five distinct taste qualities: sweet, bitter, umami (taste of amino acids), sour and salty. For bitter, sweet, and umami compounds taste signaling is initiated by binding of tastants to G protein-coupled receptors. The interactions of taste stimuli, usually watersoluble chemicals, with their cognate receptors lead to the activation of the G protein gustducin, which, in turn, initiates a signal resulting in the activation of gustatory afferents. However, details of gustatory signal transmission and processing as well as neural coding are only incompletely understood. This is partly due to the property of some tastants to elicit several sensations simultaneously, unspecific effects caused by the temperature, viscosity, osmolarity, and pH of the solvents, as well as by mechanical stimulation of the tongue during stimulus application. The analysis of gustatory processing of taste information are mainly based on mouse models after stimulation with bitter taste stimuli. Even though it is known that the mouse genome codes for 35 bitter taste receptor genes only few of them had been analysed so far. For better understanding and interpretation of animal experiments 16 mouse bitter receptors had been analysed by Calcium Imaging experiments with HEK293T cells. The data reveal that mouse bitter taste receptors are more narrow tuned than human bitter taste receptors, proving that the ligand spectra of murine and human orthologous receptors are not complient. In order to avoid the disturbing effects of solvents and stimulus application on the analysis of gustatory information transfer and processing, I employ an optogenetical approach to address this problem. For this purpose I generated three strains of gene-targeted mice in which the coding regions of the genes for the umami receptor subunit Tas1r1, the sweet receptor subunit Tas1r2 or the bitter taste receptor Tas2r114 have been replaced by the coding sequences of different opsins (photoreceptors of visual transduction) that are sensitive to light of various wavelengths. In these animals I should be able to activate sweet, bitter, or umami signalling by light avoiding any solvent effects. In initial experiments of this project I demonstrated that the various visual opsins indeed functionally couple to taste signal transduction pathway in oocyte expression system, generating basic knowledge and foundation for the generation of the gene-targeted animals. The knockout-knockin strategies have been successfully realized in the case of all three mouse models, revealed by RT-PCR, in situ hybridization and immunohistochemical analysis of taste papillae. All data confirm that the particular taste receptors have been replaced by the different opsins in taste cells. Further analysis concerning the functional consequences of opsin knockin and taste receptor knockout are part of prospective work. KW - Geschmack KW - G-Protein-gekoppelte Rezeptoren KW - Bitterrezeptoren KW - Optogenetik KW - taste KW - G protein-coupled receptors KW - bitter taste receptors KW - optogenetic Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-58059 ER - TY - CHAP A1 - Bonaventura, Klaus A1 - Sonntag, Steffen A1 - Kleber, Franz Xayer T1 - Incidence of acute thrombosis after percutaneous coronary intervention with paclitaxel eluting balloons in a clinical setting and in clinical trials T2 - Journal of the American College of Cardiology Y1 - 2011 SN - 0735-1097 VL - 58 IS - 20 SP - B78 EP - B78 PB - Elsevier CY - New York ER - TY - JOUR A1 - Melcher, Ralph A1 - Hartmann, Elena A1 - Zopf, Waltraud A1 - Herterich, Sabine A1 - Wilke, Philipp A1 - Mueller, Ludwig A1 - Rosler, Eduard A1 - Kudlich, Theodor A1 - Al-Taie, Oliver A1 - Rosenwald, Andreas A1 - Katzenberger, Tiemo A1 - Scholtka, Bettina A1 - Seibold, Stefan A1 - Rogoll, Dorothee A1 - Scheppach, Wolfgang A1 - Scheurlen, Michael A1 - Luehrs, Hardi T1 - LOH and copy neutral LOH (cnLOH) act as alternative mechanism in sporadic colorectal cancers with chromosomal and microsatellite instability JF - Carcinogenesis : a comprehensive survey N2 - Background and aims. Tumor suppressor genes are often located in frequently deleted chromosomal regions of colorectal cancers (CRCs). In contrast to microsatellite stable (MSS) tumors, only few loss of heterozygosity (LOH) studies were performed in microsatellite instable (MSI) tumors, because MSI carcinomas are generally considered to be chromosomally stable and classical LOH studies are not feasible due to MSI. The single nucleotide polymorphism (SNP) array technique enables LOH studies also in MSI CRC. The aim of our study was to analyse tissue from MSI and MSS CRC for the existence of (frequently) deleted chromosomal regions and tumor suppressor genes located therein. Methods and results. We analyzed tissues from 32 sporadic CRCs and their corresponding normal mucosa (16 MSS and 16 MSI tumors) by means of 50K SNP array analysis. MSS tumors displayed chromosomal instability that resulted in multiple deleted (LOH) and amplified regions and led to the identification of MTUS1 (8p22) as a candidate tumor suppressor gene in this region. Although the MSI tumors were chromosomally stable, we found several copy neutral LOHs (cnLOH) in the MSI tumors; these appear to be instrumental in the inactivation of the tumor suppressor gene hMLH1 and a gene located in chromosomal region 6pter-p22. Discussion. Our results suggest that in addition to classical LOH, cnLOH is an important mutational event in relation to the carcinogenesis of MSS and MSI tumors, causing the inactivation of a tumor suppressor gene without copy number alteration of the respective region; this is crucial for the development of MSI tumors and for some chromosomal regions in MSS tumors. Y1 - 2011 U6 - https://doi.org/10.1093/carcin/bgr011 SN - 0143-3334 VL - 32 IS - 4 SP - 636 EP - 642 PB - Oxford Univ. Press CY - Oxford ER - TY - CHAP A1 - Gerecke, Christian A1 - Scholtka, Bettina T1 - Detection of low level adenomatous polyposis coli(APC) gene mutatons by wild-type blocking-pcr and high resolution melting analysis T2 - Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine Y1 - 2011 SN - 1434-6621 VL - 49 IS - 1 SP - S603 EP - S603 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Henkel, Janin A1 - Gärtner, Daniela A1 - Dorn, Christoph A1 - Hellerbrand, Claus A1 - Schanze, Nancy A1 - Elz, Sheila R. A1 - Püschel, Gerhard Paul T1 - Oncostatin M produced in Kupffer cells in response to PGE(2) possible contributor to hepatic insulin resistance and steatosis JF - Laboratory investigation : the basic and translational pathology research journal ; an official journal of the United States and Canadian Academy of Pathology N2 - Hepatic insulin resistance is a major contributor to hyperglycemia in metabolic syndrome and type II diabetes. It is caused in part by the low-grade inflammation that accompanies both diseases, leading to elevated local and circulating levels of cytokines and cyclooxygenase (COX) products such as prostaglandin E-2 (PGE(2)). In a recent study, PGE(2) produced in Kupffer cells attenuated insulin-dependent glucose utilization by interrupting the intracellular signal chain downstream of the insulin receptor in hepatocytes. In addition to directly affecting insulin signaling in hepatocytes, PGE(2) in the liver might affect insulin resistance by modulating cytokine production in non-parenchymal cells. In accordance with this hypothesis, PGE(2) stimulated oncostatin M (OSM) production by Kupffer cells. OSM in turn attenuated insulin-dependent Akt activation and, as a downstream target, glucokinase induction in hepatocytes, most likely by inducing suppressor of cytokine signaling 3 (SOCS3). In addition, it inhibited the expression of key enzymes of hepatic lipid metabolism. COX-2 and OSM mRNA were induced early in the course of the development of non-alcoholic steatohepatitis (NASH) in mice. Thus, induction of OSM production in Kupffer cells by an autocrine PGE(2)-dependent feed-forward loop may be an additional, thus far unrecognized, mechanism contributing to hepatic insulin resistance and the development of NASH. KW - cyclooxygenase KW - cytokine KW - hepatic steatosis KW - NASH KW - suppressor of cytokine signaling (SOCS) KW - type II diabetes (T2DM) Y1 - 2011 U6 - https://doi.org/10.1038/labinvest.2011.47 SN - 0023-6837 VL - 91 IS - 7 SP - 1107 EP - 1117 PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Wengenmayer, Christina A1 - Krikov, Maxim A1 - Mueller, Susanne A1 - Lucht, Kristin A1 - Villringer, Arno A1 - Hocher, Berthold A1 - Unger, Thomas A1 - Thoene-Reineke, Christa T1 - Novel therapy approach in primary stroke prevention simultaneous inhibition of endothelin converting enzyme and neutral endopeptidase in spontaneously hypertensive, stroke-prone rats improves survival JF - Neurological research : a journal of progress in neurosurgery and neurosciences N2 - Objectives: Stroke, frequently a consequence of hypertension, is one of the leading causes of death and neurological disabilities worldwide. In the ischemic brain, levels of endothelin-1, one of the most potent vasoconstrictors, are raised. Anti-inflammatory and neuroprotective effects of endothelin antagonists after stroke have been described in literature. Based on these findings, we investigated the protective effect of the endothelin converting enzyme/neutral endopeptidase blocker, SLV 338, in salt-loaded, stroke-prone, spontaneously hypertensive rats. Methods: Male, 8-week-old spontaneously hypertensive stroke-prone rats were put on a high salt diet and treated with either 30 mg/kg or 100 mg/kg SLV 338 or vehicle for 27 weeks. Blood pressure, neurological outcome, body weight, and mortality were investigated throughout treatment. In weeks 1 and 9, animals were housed in metabolic cages for collection of urinary and blood samples and assessment of salt water and food intake. In weeks 22 and 27, additional blood samples were taken. At the end of the study, all brains were analyzed using magnetic resonance imaging. Results: SLV 338 was well tolerated in all animals. Neurological outcome and infarct size were similar in all groups. Albuminuria was considerably delayed and the incidence of stroke significantly lowered in treated animals. In spontaneously hypertensive stroke-prone rats, treatment with SLV 338 significantly (P=0.01) improved survival in comparison to the vehicle treated group in a blood pressure-independent manner. Discussion: Our data in spontaneously hypertensive stroke-prone rats demonstrate that combined endothelin converting enzyme/neutral endopeptidase inhibition could offer a new therapeutic approach for primary stroke prevention and improvement of mortality. The mechanism seems to be blood pressure-independent. KW - Endothelin KW - Hypertension KW - Natriuretic peptides KW - Stroke Y1 - 2011 U6 - https://doi.org/10.1179/016164111X12881719352534 SN - 0161-6412 VL - 33 IS - 2 SP - 201 EP - 207 PB - Routledge, Taylor & Francis Group CY - Leeds ER - TY - THES A1 - Behrens, Maik T1 - Molekularbiologie menschlicher Bittergeschmacksrezeptoren Y1 - 2011 CY - Potsdam ER - TY - THES A1 - Schüler, Rita T1 - Identifizierung und Charakterisierung neuer natürlicher Liganden des Peroxisomen-Proliferator aktivierten Rezeptors y (PPARy) Y1 - 2011 CY - Potsdam ER - TY - THES A1 - Flehmig, Karin Gesine T1 - Evaluation des BCM-Programms der PreCon GmbH & Co. nach MIRA-Konzept Y1 - 2011 CY - Potsdam ER - TY - THES A1 - Schulz, Nadja T1 - Die Rolle der 3-L-Hydroxyacyl-Coenzym-A-Dehydrogenase in der Regulation des örpergewichts, der Thermogenese sowie der Glucosehomöostase Y1 - 2011 CY - Potsdam ER - TY - THES A1 - Mirhashemi, Farshad T1 - Einfluss von Fetten und Kohlenhydraten auf die Entwicklung der Insulinresistenz und des Typ-2-Diabetes in verschiedenen Mausmodellen Y1 - 2011 CY - Potsdam ER - TY - THES A1 - Becker, Natalie T1 - Etablierung des Modells einer simplifizierten humanen Darmmikrobiota in gnotobiotischen Ratten und Anwendung der definierten Mikrobiota im chemischen induzierten Kolonkanzerogenesemodell Y1 - 2011 CY - Potsdam ER - TY - THES A1 - Fleißner, Christine T1 - Einfluss der gastrointestinalen Mikrobiota auf den Energiestoffwechsel und die Entstehung von Adipositas im Mausmodell Y1 - 2011 CY - Potsdam ER - TY - THES A1 - Keipert, Susanne T1 - The effects of mitochondrial uncoupling in skeletal muscle on lifespan, substrate and energy metabolism in mice Y1 - 2011 CY - Potsdam ER - TY - THES A1 - Freudenberg, Anne T1 - Effects of high-protein diets and leucine supplementation on the metabolic syndrome in mice Y1 - 2011 CY - Potsdam ER - TY - JOUR A1 - Rade-Kukic, Koralja A1 - Schmitt, C. A1 - Rawel, Harshadrai Manilal T1 - Formation of conjugates between beta-lactoglobulin and allyl isothiocyanate effect on protein heat aggregation, foaming and emulsifying properties JF - Food hydrocolloids N2 - Whey proteins are widely used food ingredients due to their nutritional and functional properties (gelling, emulsifying, foaming). Owning to their structure (free thiol group, lysine residues, hydrophobic pocket), they can also be used as carriers for bioactives. In this study, conjugates between beta-lactoglobulin (beta-lg), and a bioactive metabolite from Brassicaceae vegetables, allyl isothiocyanate (AITC) were formed. Heat aggregation behavior (85 degrees C, 15 min), foaming and emulsifying properties of conjugates, at pH 4.0 and 7.1, were evaluated. Conjugates were formed by incubating beta-lg (0.5 mM) with AITC (0.05-20 mM) in water at pH 8.5 and room temperature. AITC primarily reacted with beta-lg's free thiol group (K-D = 0.2 +/- 0.1 mM) and thereafter with its amino groups (K-D 10.8 +/- 3.4 mM). AITC binding destabilized secondary and tertiary structure of beta-lg at pH 7.1, whereas induced molten globule conformation at pH 4.0. Conjugation reduced the heat aggregation of beta-lg at pH 7.1, while promoting it at pH 4.0. Conjugates adsorbed faster to air/water and oil/water interfaces at pH 4.0 than at pH 7.1. After 30 min, air/water surface tension was lower at pH 4.0 (47 mN m(-1)) than at pH 7.1 (57 mN m(-1)), while the surface tension of the oil/water interface was 8 mN m(-1) at both pHs. Foams produced with beta-lg-AITC conjugates at pH 4.0 exhibited higher volume and liquid stabilities compared to foams obtained at pH 7.1. Emulsions formed with conjugates at both pHs were destabilized by creaming due to flocculation, but coalescence was prevented. This study revealed that whey protein could potentially be used for the delivery of isothiocyanates in the form of foam or emulsion-based products. KW - beta-Lactoglobulin KW - Allyl isothiocyanate KW - Molecular structure KW - Heat aggregation KW - Foaming properties KW - Emulsifying properties Y1 - 2011 U6 - https://doi.org/10.1016/j.foodhyd.2010.08.018 SN - 0268-005X VL - 25 IS - 4 SP - 694 EP - 706 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Schweigert, Florian J. A1 - Reimann, J. T1 - Micronutrients and their Relevance for the Eye - Function of Lutein, Zeaxanthin and Omega-3 Fatty Acids JF - Klinische Monatsblätter für Augenheilkunde N2 - Micronutrients play an important role in function and health maintenance for the eye. Especially lutein, zeaxanthin and omega-3 fatty acids perform remarkable functions: lutein together with zeaxanthin forms the macular pigment, these carotenoids filter out the damaging blue light component from the sunlight as well as the ultraviolet light which leads to improved contrast sensitivity and less problems with screen glare. Furthermore, the macular pigment has antioxidant and anti-inflammatory effects. The omega-3 fatty acids also possess anti-inflammatory effects and, when converted into neuroprotectin, they protect against oxidative induced apoptosis in the retina. They are also responsible for the fluidity and supply to the photoreceptor membrane. These properties are important for the prevention and treatment of degenerative eye diseases like age-related macular degeneration. However, older people are often not sufficiently supplied of micronutrients in their diet. Because the supply of nutrients can hardly be achieved by dietary change, the additional intake in the form of food supplements is useful in this age group. Scientific studies have shown the positive effects of supplementation with micronutrients such as lutein/zeaxanthin, vitamin C, vitamin E, zinc and omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid (DHA and EPA). Currently available nutritional products are based in part on the ingredients of the ARED study (Age Related Eye Disease Study). According to more recent studies formulations containing lutein and omega-3 fatty acids in physiologically meaningful doses without additional beta-carotene should be preferred. 10 to 20 mg of lutein and zeaxanthin represent a safe daily dose Regarding to the context above, beta-carotene in high doses plays a minor role to the eye and is especially critical for the health of smokers. This paper summarises the functions of the presented micronutrients in the eye and can assist ophthalmologists in advising their patients. KW - AMD KW - lutein KW - omega-3 fatty acids KW - macular pigment density KW - micronutrients KW - dosage recommendation Y1 - 2011 U6 - https://doi.org/10.1055/s-0029-1245527 SN - 0023-2165 VL - 228 IS - 6 SP - 537 EP - 543 PB - Thieme CY - Stuttgart ER - TY - JOUR A1 - Raila, Jens A1 - Schweigert, Florian J. A1 - Kohn, Barbara T1 - C-reactive protein concentrations in serum of dogs with naturally occurring renal disease JF - Journal of veterinary diagnostic investigation N2 - The current study was undertaken to investigate the relation between serum C-reactive protein (CRP) concentrations and parameters of renal function in dogs with naturally occurring renal disease. Dogs were assigned to groups according to plasma creatinine concentration, urinary protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P-Cl(Cr)) rates. Group A (healthy control dogs; n = 8): non-azotemic (plasma creatinine <125 mu mol/l) and nonproteinuric (UP/UC <0.2), with P-Cl(Cr) rates >90 ml/min/m(2); group B (n = 11): non-azotemic, nonproteinuric dogs with reduced P-Cl(Cr) rates (50-89 ml/min/m(2)); group C (n = 7): azotemic, borderline proteinuric dogs (P-Cl(Cr) rates: 22-67 ml/min/m(2)); and group D (n = 6): uremic, proteinuric dogs (not tested for P-Cl(Cr)). The serum CRP concentrations were measured via commercial enzyme-linked immunosorbent assay. The CRP concentrations in the clinically healthy dogs (group A) ranged from 2.09 mg/l to 8.60 mg/l (median: 3.21 mg/l). In comparison with dogs of group A, median CRP concentrations were significantly (P < 0.01) elevated in dogs of group B (17.6 mg/l, range: 17.0-19.2 mg/l), group C (24.8 mg/l, range: 18.0-32.5 mg/l), and group D (59.7 mg/l, range: 17.7-123 mg/l). Serum CRP was significantly related to P-Cl(Cr) (r = -0.83; P < 0.001), plasma creatinine (r = 0.81; P < 0.001), UP/UC (r = 0.70; P < 0.001), and leukocytes (r = 0.49; P < 0.01). The significant relations between serum CRP concentrations and biochemical parameters of kidney function in plasma and urine suggest that a stimulation of the acute phase response is implicated in the pathogenesis of canine renal disease. KW - C-reactive protein KW - dogs KW - proteinuria KW - renal disease Y1 - 2011 U6 - https://doi.org/10.1177/1040638711407896 SN - 1040-6387 VL - 23 IS - 4 SP - 710 EP - 715 PB - Sage Publ. CY - Thousand Oaks ER - TY - JOUR A1 - Milcu, Alexandru A1 - Heim, Angela A1 - Ellis, Richard J. A1 - Scheu, Stefan A1 - Manning, Pete T1 - Identification of general patterns of nutrient and labile carbon control on soil carbon dynamics across a successional gradient JF - Ecosystems N2 - Carbon (C) inputs and nutrient availability are known to affect soil organic carbon (SOC) stocks. However, general rules regarding the operation of these factors across a range of soil nutrient availabilities and substrate qualities are unidentified. "Priming" (stimulated decomposition by labile C inputs) and 'preferential substrate utilization' (retarded decomposition due to shifts in community composition towards microbes that do not mineralize SOC) are two hypotheses to explain effects of labile C additions on SOC dynamics. For effects of nutrient additions (nitrogen and phosphorus) on SOC dynamics, the stoichiometric (faster decomposition of materials of low carbon-to-nutrient ratios) and 'microbial mining' (that is, reduced breakdown of recalcitrant C forms for nutrients under fertile conditions) hypotheses have been proposed. Using the natural gradient of soil nutrient availability and substrate quality of a chronosequence, combined with labile C and nutrient amendments, we explored the support for these contrasting hypotheses. Additions of labile C, nitrogen (N), phosphorus (P), and combinations of C and N and C and P were applied to three sites: 2-year fallow grassland, mature grassland and forest, and the effects of site and nutrient additions on litter decomposition and soil C dynamics were assessed. The response to C addition supported the preferential substrate hypothesis for easily degradable litter C and the priming hypothesis for SOC, but only in nitrogen-enriched soils of the forest site. Responses to N addition supported the microbial mining hypothesis irrespective of C substrate (litter or SOC), but only in the forest site. Further, P addition effects on SOC support the stoichiometric hypothesis; P availability appeared key to soil C release (priming) in the forest site if labile C and N is available. These results clearly link previously contrasting hypotheses of the factors controlling SOC with the natural gradient in litter quality and nutrient availability that exists in ecosystems at different successional stages. A holistic theory that incorporates this variability of responses, due to different mechanisms, depending on nutrient availability and substrate quality is essential for devising management strategies to safeguard soil C stocks. KW - carbon sequestration KW - priming effect KW - microbial mining KW - succession KW - microorganisms KW - litter decomposition Y1 - 2011 U6 - https://doi.org/10.1007/s10021-011-9440-z SN - 1432-9840 VL - 14 IS - 5 SP - 710 EP - 719 PB - Springer CY - New York ER - TY - JOUR A1 - Thawnashom, Kittisak A1 - Tungtrongchitr, Rungsunn A1 - Chanchay, Siriporn A1 - Tungtrongchitr, Anchalee A1 - Raila, Jens A1 - Henze, Andrea A1 - Schweigert, Florian J. T1 - Association between Retinol-Binding protein and renal function among Asian subjects with type 2 diabetes mellitus a cross-sectionaö study JF - The Southeast Asian journal of tropical medicine and public health : official publication of the SEAMEO Regional Tropical Medicine and Public Health Project (TROPMED) N2 - Retinol-binding protein 4 (RBP4) has been suggested as new adipokine, possibly linking obesity to type 2 diabetes mellitus (T2DM). Since the kidneys are the main site of RBP4 degradation and since renal failure is a frequent co-morbid condition with diabetes mellitus, we evaluated the association among RBP4, renal function and T2DM in an Asian population. RBP4 serum levels were analyzed in 110 subjects (50 with T2DM) using an enzyme-linked immunosorbent assay (ELISA). Based on a cut-off estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m(2) (calculated according the abbreviated MDRD formula which uses serum creatinine level, age and gender) and on the T2DM status, subjects were assigned to four subgroups: Group A - controls with an eGFR > 60 ml/min per 1.73 m(2), Group B - controls with an eGFR < 60 ml/min per 1.73 m(2), Group C- T2DM subjects with an eGFR>60 ml/min per 1.73 m(2), and Group D - T2DM subjects with an eGFR <60 ml/ mm per 1.73 m(2). In both the T2DM and control groups, RBP4 levels were higher in subjects with an eGFR < 60 ml/min per 1.73 m(2) than in subjects with an eGFR >60 ml/min per 1.73 m(2). However, the difference was only significant between the control groups (p <0.05). After adjusting for age, gender, BMI, eGFR and the presence of T2DM, eGFR, not T2DM, was associated with plasma RBP4 levels (p<0.05). These results suggest among Asians the eGFR, but not the presence of T2DM, is a major determinant of RBP4 serum levels. The eGFR should be taken into account when evaluating the role of RBP4 in the pathogenesis of insulin resistance and T2DM. KW - retinol-binding protein 4 KW - renal function KW - type 2 diabetes mellitus KW - Asian subjects Y1 - 2011 SN - 0125-1562 VL - 42 IS - 4 SP - 936 EP - 945 PB - SEAMEO CY - Bangkok ER - TY - JOUR A1 - Geschka, Sandra A1 - Kretschmer, Axel A1 - Sharkovska, Yuliya A1 - Evgenov, Oleg V. A1 - Lawrenz, Bettina A1 - Hucke, Andreas A1 - Hocher, Berthold A1 - Stasch, Johannes-Peter T1 - Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive dahl rats JF - PLoS one N2 - Background: A direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO) and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension. Methods and Results: Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d) for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1. Conclusions: Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions. Y1 - 2011 U6 - https://doi.org/10.1371/journal.pone.0021853 SN - 1932-6203 VL - 6 IS - 7 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Kuhl, Juliane A1 - Winterhoff, Nora A1 - Wulf, Manuela A1 - Schweigert, Florian J. A1 - Schwendenwein, Ilse A1 - Bruckmaier, Rupert M. A1 - Aurich, Jörg E. A1 - Kutzer, Peter A1 - Aurich, Christine T1 - Changes in faecal bacteria and metabolic parameters in foals during the first six weeks of life JF - Veterinary microbiology N2 - Many foals develop diarrhoea within the first two weeks of life which has been suggested to coincide with postpartum oestrus in their dams. To analyse the pathogenesis of this diarrhoea we have determined faecal bacteria in foals and their dams (n = 30 each), and serum IGF-1 and gamma-globulins for 6 weeks after birth. In addition, effects of beta-carotene supplementation to mares (group 1: 1000 mg/day, n = 15, group 2: control, n = 15) on diarrhoea in foals were studied. Diarrhoea occurred in 92 and 79% of foals in groups 1 and 2, respectively, but was not correlated with oestrus in mares. Beta-carotene supplementation was without effect on foal diarrhoea. In mares, bacterial flora remained stable. The percentage of foals with cultures positive for E. coli was low at birth but increased within one day, the percentage positive for Enterococcus sp. was low for 10 days and for Streptococcus sp. and Staphylococcus sp. was low for 2-4 weeks. By 4 weeks of age, bacterial flora in foals resembled an adult pattern. Concentration of serum IGF-1 was low at birth (group 1:149 +/- 11, group 2:166 17 ng/ml), increased after day 1 (day 7 group 1:384 +/- 30, group 2: 372 +/- 36) but at no time differed between groups. Serum gamma-globulin concentration in foals was low before colostrum intake and highest on day 1 (p < 0.001 over time). In conclusion, neonatal diarrhoea in foals does not coincide with postpartum oestrus in their dams but with changes in intestinal bacteria and is not influenced by beta-carotene supplementation given to mares. KW - Foal KW - Diarrhoea KW - Faecal bacteria KW - IGF-1 KW - Carotene supplementation Y1 - 2011 U6 - https://doi.org/10.1016/j.vetmic.2011.03.017 SN - 0378-1135 VL - 151 IS - 3-4 SP - 321 EP - 328 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Barcelo-Coblijn, Gwendolyn A1 - Laura Martin, Maria A1 - de Almeida, Rodrigo F. M. A1 - Antonia Noguera-Salva, Maria A1 - Marcilla-Etxenike, Amaia A1 - Guardiola-Serrano, Francisca A1 - Lueth, Anja A1 - Kleuser, Burkhard A1 - Halver, John E. A1 - Escriba, Pablo V. T1 - Sphingomyelin and sphingomyelin synthase (SMS) in the malignant transformation of glioma cells and in 2-hydroxyoleic acid therapy JF - Proceedings of the National Academy of Sciences of the United States of America N2 - The mechanism of action of 2-hydroxyoleic acid (2OHOA), a potent antitumor compound, has not yet been fully elucidated. Here, we show that human cancer cells have markedly lower levels of sphingomyelin (SM) than nontumor (MRC-5) cells. In this context, 2OHOA treatment strongly augments SM mass (4.6-fold), restoring the levels found in MRC-5 cells, while a loss of phosphatidylethanolamine and phosphatidylcholine is observed (57 and 30%, respectively). The increased SM mass was due to a rapid and highly specific activation of SM synthases (SMS). This effect appeared to be specific against cancer cells as it did not affect nontumor MRC-5 cells. Therefore, low SM levels are associated with the tumorigenic transformation that produces cancer cells. SM accumulation occurred at the plasma membrane and caused an increase in membrane global order and lipid raft packing in model membranes. These modifications would account for the observed alteration by 2OHOA in the localization of proteins involved in cell apoptosis (Fas receptor) or differentiation (Ras). Importantly, SMS inhibition by D609 diminished 2OHOA effect on cell cycle. Therefore, we propose that the regulation of SMS activity in tumor cells is a critical upstream event in 2OHOA antitumor mechanism, which also explains its specificity for cancer cells, its potency, and the lack of undesired side effects. Finally, the specific activation of SMS explains the ability of this compound to trigger cell cycle arrest, cell differentiation, and autophagy or apoptosis in cancer cells. KW - anticancer KW - membrane-lipid therapy KW - lung cancer KW - membrane lipids Y1 - 2011 U6 - https://doi.org/10.1073/pnas.1115484108 SN - 0027-8424 VL - 108 IS - 49 SP - 19569 EP - 19574 PB - National Acad. of Sciences CY - Washington ER - TY - JOUR A1 - Chaykovska, Lyubov A1 - von Websky, Karoline A1 - Rahnenführer, Jan A1 - Alter, Markus L. A1 - Heiden, Susi A1 - Fuchs, Holger A1 - Runge, Frank A1 - Klein, Thomas A1 - Hocher, Berthold T1 - Effects of DPP-4 Inhibitors on the Heart in a Rat Model of Uremic Cardiomyopathy JF - PLoS one N2 - Background: Uremic cardiomyopathy contributes substantially to mortality in chronic kidney disease (CKD) patients. Glucagon-like peptide-1 (GLP-1) may improve cardiac function, but is mainly degraded by dipeptidyl peptidase-4 (DPP-4). Methodology/Principal Findings: In a rat model of chronic renal failure, 5/6-nephrectomized [5/6N] rats were treated orally with DPP-4 inhibitors (linagliptin, sitagliptin, alogliptin) or placebo once daily for 4 days from 8 weeks after surgery, to identify the most appropriate treatment for cardiac dysfunction associated with CKD. Linagliptin showed no significant change in blood level AUC(0-infinity) in 5/6N rats, but sitagliptin and alogliptin had significantly higher AUC(0-infinity) values; 41% and 28% (p=0.0001 and p=0.0324), respectively. No correlation of markers of renal tubular and glomerular function with AUC was observed for linagliptin, which required no dose adjustment in uremic rats. Linagliptin 7 mu mol/kg caused a 2-fold increase in GLP-1 (AUC 201.0 ng/l*h) in 5/6N rats compared with sham-treated rats (AUC 108.6 ng/l*h) (p=0.01). The mRNA levels of heart tissue fibrosis markers were all significantly increased in 5/6N vs control rats and reduced/normalized by linagliptin. Conclusions/Significance: DPP-4 inhibition increases plasma GLP-1 levels, particularly in uremia, and reduces expression of cardiac mRNA levels of matrix proteins and B-type natriuretic peptides (BNP). Linagliptin may offer a unique approach for treating uremic cardiomyopathy in CKD patients, with no need for dose-adjustment. Y1 - 2011 U6 - https://doi.org/10.1371/journal.pone.0027861 SN - 1932-6203 VL - 6 IS - 11 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Henze, Andrea A1 - Raila, Jens A1 - Kempf, Caroline A1 - Reinke, Petra A1 - Sefrin, Anett A1 - Querfeld, Uwe A1 - Schweigert, Florian J. T1 - Vitamin A metabolism is changed in donors after living-kidney transplantation an observational study JF - Lipids in health and disease N2 - Background: The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT. Results: As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months. Conclusion: LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors. KW - Donors KW - glomerular filtration rate KW - kidney transplantation KW - retinol KW - retinol-binding protein 4 KW - transthyretin Y1 - 2011 U6 - https://doi.org/10.1186/1476-511X-10-231 SN - 1476-511X VL - 10 IS - 23 PB - BioMed Central CY - London ER - TY - JOUR A1 - Espe, Katharina M. A1 - Raila, Jens A1 - Henze, Andrea A1 - Krane, Vera A1 - Schweigert, Florian J. A1 - Hocher, Berthold A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Impact of vitamin A on clinical outcomes in haemodialysis patients JF - Nephrology, dialysis, transplantation N2 - Background. Patients on maintenance haemodialysis treatment experience an excessive risk of cardiovascular disease and mortality. The vitamin A concentration is known to be higher in these patients compared to the general population where elevated vitamin A concentrations are associated with adverse outcome. The impact of vitamin A on morbidity and mortality in end-stage renal disease patients is controversial and is the topic of this study. Methods. We analysed plasma retinol and retinol-binding protein 4 (RBP4) in 1177 diabetic haemodialysis patients, who participated in the German Diabetes and Dialysis Study (median follow-up 4 years). By Cox regression analyses hazard ratios (HRs) were determined for pre-specified, adjudicated end points according to baseline concentrations. Results. Patients had a mean age of 66 +/- 8 years, mean retinol and RBP4 concentrations of 3.28 (0.71-7.44) and 4.02 (1.28-10.1) mu mol/L, respectively. Patients with retinol concentrations in the first quartile (<2.6 mu mol/L) had an almost 2-fold increased risk of all-cause mortality compared to patients of the fourth quartile [>3.9 mu mol/L; HR 1.81, 95% confidence interval (CI) 1.43-2.30]. There was a strong association between low retinol and the risk of sudden cardiac death (SCD, HR 2.22, 95% CI 1.41-3.50) and fatal infection (HR 2.19, 95% CI 1.26-3.82). Patients with RBP4 concentrations in the lowest quartile (<3.0 mu mol/L) were more likely to die of any cause (HR 1.43, 95% CI 1.14-1.80), experience SCD (HR 1.97, 95% CI 1.28-3.03) and cardiovascular events (HR 1.43, 95% CI 1.10-1.85). Conclusion. This large cohort study shows a strong association of low retinol and RBP4 concentrations with SCD and all-cause mortality in diabetic haemodialysis patients. KW - haemodialysis KW - mortality KW - retinol KW - retinol-binding protein 4 KW - sudden death Y1 - 2011 U6 - https://doi.org/10.1093/ndt/gfr171 SN - 0931-0509 VL - 26 IS - 12 SP - 4054 EP - U583 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Vignon-Zellweger, Nicolas A1 - Relle, Katharina A1 - Kienlen, Elodie A1 - Alter, Markus L. A1 - Seider, Patrick A1 - Sharkovska, Juliya A1 - Heiden, Susi A1 - Kalk, Philipp A1 - Schwab, Karima A1 - Albrecht-Kuepper, Barbara A1 - Theuring, Franz A1 - Stasch, Johannes-Peter A1 - Hocher, Berthold T1 - Endothelin-1 overexpression restores diastolic function in eNOS knockout mice JF - Journal of hypertension N2 - Background The cardiac nitric oxide and endothelin-1 (ET-1) systems are closely linked and play a critical role in cardiac physiology. The balance between both systems is often disturbed in cardiovascular diseases. To define the cardiac effect of excessive ET-1 in a status of nitric oxide deficiency, we compared left ventricular function and morphology in wild-type mice, ET-1 transgenic (ET+/+) mice, endothelial nitric oxide synthase knockout (eNOS(-/-)) mice, and ET(+/+)eNOS(-/-) mice. Methods and results eNOS(-/-) and ET(+/+)eNOS(-/-) mice developed high blood pressure compared with wild-type and ET+/+ mice. Left ventricular catheterization showed that eNOS(-/-) mice, but not ET(+/+)eNOS(-/-), developed diastolic dysfunction characterized by increased end-diastolic pressure and relaxation constant tau. To elucidate the causal molecular mechanisms driving the rescue of diastolic function in ET(+/+)eNOS(-/-) mice, the cardiac proteome was analyzed. Two-dimensional gel electrophoresis coupled to mass spectrometry offers an appropriate hypothesis-free approach. ET-1 overexpression on an eNOS(-/-) background led to an elevated abundance and change in posttranslational state of antioxidant enzymes (e. g., peroxiredoxin-6, glutathione S-transferase mu 2, and heat shock protein beta 7). In contrast to ET(+/+)eNOS(-/-) mice, eNOS(-/-) mice showed an elevated abundance of proteins responsible for sarcomere disassembly (e. g., cofilin-1 and cofilin-2). In ET(+/+)eNOS(-/-) mice, glycolysis was favored at the expense of fatty acid oxidation. Conclusion eNOS(-/-) mice developed diastolic dysfunction; this was rescued by ET-1 transgenic overexpression. This study furthermore suggests that cardiac ET-1 overexpression in case of eNOS deficiency causes specifically the regulation of proteins playing a role in oxidative stress, myocytes contractility, and energy metabolism. KW - cardiovascular diseases KW - endothelin KW - nitric oxide Y1 - 2011 U6 - https://doi.org/10.1097/HJH.0b013e3283450770 SN - 0263-6352 SN - 1473-5598 VL - 29 IS - 5 SP - 961 EP - 970 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Lamy, Elsa A1 - Rawel, Harshadrai Manilal A1 - Schweigert, Florian J. A1 - Capela e Silva, Fernando A1 - Ferreira, Ana A1 - Costa, Ana Rodrigues A1 - Antunes, Celia A1 - Almeida, Andre Martinho A1 - Coelho, Ana Varela A1 - Sales-Baptista, Elvira T1 - The effect of tannins on mediterranean ruminant ingestive behavior the role of the oral cavity JF - Molecules N2 - Sheep, cattle and goat are domestic ruminants of significant economic interest in the Mediterranean region. Although sharing the same pasture ranges, they ingest different plants and plant parts and, consequently different levels of tannins. This suggests an ability to detect and adapt ingestion according to animal physiological limits of tolerance for plant secondary metabolites. This review will detail the effects of dietary tannins on feeding behavior, and the role of the oral cavity in this process, with focus on such ruminant species. The role of salivary protein profile in tannin perception in the oral cavity, and as a defense mechanism, will be discussed. KW - polyphenols KW - diet selection KW - ruminants KW - salivary proteins KW - tannin-protein interaction Y1 - 2011 U6 - https://doi.org/10.3390/molecules16042766 SN - 1420-3049 VL - 16 IS - 4 SP - 2766 EP - 2784 PB - MDPI CY - Basel ER - TY - CHAP A1 - Pfab, T. A1 - Sharkovska, Yukiya A1 - Alter, Markus L. A1 - von Websky, Karoline A1 - Mark, M. A1 - Klein, T. A1 - Hocher, Berthold T1 - Effect of linagliptin on infarction size and cardiac function in rats after myocardial ischaemia reperfusion T2 - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) Y1 - 2011 SN - 0012-186X VL - 54 SP - S329 EP - S329 PB - Springer CY - New York ER - TY - JOUR A1 - Li, Jian A1 - Wang, Zi-Neng A1 - Schlemm, Ludwig A1 - Pfab, Thiemo A1 - Xiao, Xiao-Min A1 - Chen, You-Peng A1 - Hocher, Berthold T1 - Low birth weight and elevated head-to-abdominal circumference ratio are associated with elevated fetal glycated serum protein concentrations JF - Journal of hypertension N2 - Objective To analyze the association between low birth weight, head-to-abdominal circumference ratio, and insulin resistance in early life. Method and results Glycated serum proteins (GSPs) were quantified at delivery in 612 Chinese mother/child pairs serving as a surrogate of maternal and fetal glycemia. Differential ultrasound examination of the fetal's body (head circumference, biparietal diameter, pectoral diameter, abdominal circumference, and femur length) was done in average 1 week prior to delivery. Multivariable regression analysis considering gestational age at delivery, the child's sex, maternal BMI, maternal age at delivery, maternal body weight, and pregnancyinduced hypertension revealed that fetal GSP was inversely associated with birth weight (R(2) = 0.416; P < 0.001). Fetal GSP was furthermore positively associated with the head-to-abdominal circumference ratio, whereas the maternal GSP was negatively correlated with the offspring's head-to-abdominal circumference ratio (R(2) = 0.285; P = 0.010 and R(2) = 0.261; P = 0.020, respectively). The increased head-to-abdominal circumference ratio in newborns with higher fetal GSP is mainly due to a reduced abdominal circumference rather than reduced growth of the brain. Conclusion The disproportional intrauterine growth is in line with the concept of so-called brain sparing, a mechanism maintaining the intrauterine growth of the brain at the expense of trunk growth. Our data suggest that the low birth weight phenotype, linked to cardiovascular diseases like hypertension in later life, might be a phenotype of disproportional intrauterine growth retardation and early life insulin resistance. KW - disproportional intrauterine growth retardation KW - insulin resistance KW - low birth weight KW - ultrasound Y1 - 2011 U6 - https://doi.org/10.1097/HJH.0b013e328349a2e6 SN - 0263-6352 VL - 29 IS - 9 SP - 1712 EP - 1718 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Rohner, Fabian A1 - Frey, Simone K. A1 - Mothes, Ralf A1 - Hurtienne, Andrea A1 - Hartong, Simone A1 - Bosso, Patrice Emery A1 - Bui, Mai A1 - Schweigert, Florian J. A1 - Northrop-Clewes, Christine T1 - Quantification of vitamin A in palm oil using a fast and simple portable device method validation and comparison to high-performance liquid chromatography JF - International journal for vitamin and nutrition research N2 - Vitamin A deficiency continues to be a global public health problem. Fortification of oil with vitamin A is considered a cost-effective, feasible strategy to prevent this problem but quality control poses a challenge to program implementation. To overcome this, we have validated a newly developed device that quantitatively measures the content of retinyl palmitate in refined palm oil, is simple to use, and yields immediate results. Linearity of analysis rand from 2.5-30 mg retinol equivalents (RE)/kg of palm oil, with 2.5 mg RE/kg being the determination limit; inter- and intra-assay precision ranged from 1.4-7.1 To. Comparison with a high-performance Liquid chromatography method showed high agreement between the methods (R-2 = 0.92; Limits of Agreement: -1.24 mg to 2.53 mg RE/kg), and further comparisons illustrate that the new device is useful in low resource settings. This device offers a field- and user-friendly solution to quantifying the vitamin A content in refined palm oil. KW - Vitamin A KW - retinyl palmitate KW - fortification KW - monitoring KW - rapid test kit KW - palm oil Y1 - 2011 U6 - https://doi.org/10.1024/0300-9831/a000081 SN - 0300-9831 VL - 81 IS - 5 SP - 335 EP - 342 PB - Hogrefe CY - Bern ER - TY - JOUR A1 - Hocher, Berthold A1 - Schlemm, Ludwig A1 - Haumann, Hannah A1 - Li, Jian A1 - Rahnenführer, Jan A1 - Guthmann, Florian A1 - Bamberg, Christian A1 - Kalk, Philipp A1 - Pfab, Thiemo A1 - Chen, You-Peng T1 - Offspring sex determines the impact of the maternal ACE I/D polymorphism on maternal glycaemic control during the last weeks of pregnancy JF - Journal of the renin angiotensin aldosterone system N2 - Hypothesis/Introduction: We recently demonstrated that fetal sex may affect maternal glycaemic control in genetically prone mothers. We tested the hypothesis that fetal sex/fetal Y/X chromosomes might affect maternal glycaemic control during pregnancy depending on the maternal angiotensin converting enzyme (ACE) I/D polymorphism. Material and methods: One thousand, three hundred and thirty-two Caucasian women without pre-existing diabetes and pre-existing hypertension with singleton pregnancies delivering consecutively at the Charite obstetrics department were genotyped. Glycaemic control was analysed by measuring total glycated haemoglobin at birth. Correction for confounding factors and multiple testing was done. Results: Maternal ACE I/D polymorphism showed significant interaction with fetal sex concerning maternal total glycated haemoglobin. Total glycated haemoglobin in DD mothers delivering boys was 6.42 +/- 0.70% vs. 6.21 +/- 0.66% in DD mother delivering girls (p < 0.005), whereas the II carrying mothers showed the opposite effect. II mothers delivering a girl had a higher (p = 0.044) total glycated haemoglobin at birth (6.40 +/- 0.80%) compared to II mothers delivering boys (6.21 +/- 0.81%). There was no interaction of the ACE I/D polymorphism and fetal sex with respect to new onset proteinuria, new onset edema and pregnancy-induced hypertension. Conclusions: Maternal glycaemic control during the last weeks of pregnancy seems to be influenced by an interaction of the ACE I/D genotyp and fetal sex. KW - ACE I/D polymorphism KW - pregnancy KW - fetal sex KW - pregnancy induced diabetes KW - total glycated hemoglobin KW - glycemic control during pregnancy Y1 - 2011 U6 - https://doi.org/10.1177/1470320310387843 SN - 1470-3203 VL - 12 IS - 3 SP - 254 EP - 261 PB - Sage Publ. CY - London ER - TY - JOUR A1 - Schildroth, Janice A1 - Rettig-Zimmermann, Juliane A1 - Kalk, Philipp A1 - Steege, Andreas A1 - Faehling, Michael A1 - Sendeski, Mauricio A1 - Paliege, Alexander A1 - Lai, En Yin A1 - Bachmann, Sebastian A1 - Persson, Pontus B. A1 - Hocher, Berthold A1 - Patzak, Andreas T1 - Endothelin type A and B receptors in the control of afferent and efferent arterioles in mice JF - Nephrology, dialysis, transplantation N2 - Background. Endothelin 1 contributes to renal blood flow control and pathogenesis of kidney diseases. The differential effects, however, of endothelin 1 (ET-1) on afferent (AA) and efferent arterioles (EA) remain to be established. Methods. We investigated endothelin type A and B receptor (ETA-R, ETB-R) functions in the control of AA and EA. Arterioles of ETB-R deficient, rescued mice [ETB (-/-)] and wild types [ETB(+/+)] were microperfused. Results. ET-1 constricted AA stronger than EA in ETB (-/-) and ETB(+/+) mice. Results in AA: ET-1 induced similar constrictions in ETB(-/-) and ETB(+/+) mice. BQ-123 (ETA-R antagonist) inhibited this response in both groups. ALA-ET-1 and IRL1620 (ETB-R agonists) had no effect on arteriolar diameter. L-NAME did neither affect basal diameters nor ET-1 responses. Results in EA: ET-1 constricted EA stronger in ETB(+/+) compared to ETB(-/-). BQ-123 inhibited the constriction completely only in ETB(-/-). ALA-ET-1 and IRL1620 constricted only arterioles of ETB(+/+) mice. L-NAME decreased basal diameter in ETB(+/+), but not in ETB(-/-) mice and increased the ET-1 response similarly in both groups. The L-NAME actions indicate a contribution of ETB-R in basal nitric oxide (NO) release in EA and suggest dilatory action of ETA-R in EA. Conclusions. ETA-R mediates vasoconstriction in AA and contributes to vasoconstriction in EA in this mouse model. ETB-R has no effect in AA but mediates basal NO release and constriction in EA. The stronger effect of ET-1 on AA supports observations of decreased glomerular filtration rate to ET-1 and indicates a potential contribution of ET-1 to the pathogenesis of kidney diseases. KW - endothelin KW - ETB receptor-deficient mouse KW - glomerular arterioles KW - renal haemodynamics Y1 - 2011 U6 - https://doi.org/10.1093/ndt/gfq534 SN - 0931-0509 VL - 26 IS - 3 SP - 779 EP - 789 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Hocher, Berthold A1 - Heiden, Susi A1 - von Websky, Karoline A1 - Arafat, Ayman M. A1 - Rahnenführer, Jan A1 - Alter, Markus L. A1 - Kalk, Philipp A1 - Ziegler, Dieter A1 - Fischer, Yvan A1 - Pfab, Thiemo T1 - Renal effects of the novel selective adenosine A(1) receptor blocker SLV329 in experimental liver cirrhosis in rats JF - PLoS one N2 - Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A(1) receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A(1) receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (-36.5%, p < 0.05), especially in those receiving furosemide (-41.9%, p < 0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p < 0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A(1) receptor antagonists are clinically beneficial at different stages of liver cirrhosis. Y1 - 2011 U6 - https://doi.org/10.1371/journal.pone.0017891 SN - 1932-6203 VL - 6 IS - 3 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Grahn, R. A. A1 - Kurushima, J. D. A1 - Billings, N. C. A1 - Grahn, J. C. A1 - Halverson, J. L. A1 - Hammer, E. A1 - Ho, C. K. A1 - Kun, T. J. A1 - Levy, J. K. A1 - Lipinski, M. J. A1 - Mwenda, J. M. A1 - Ozpinar, H. A1 - Schuster, R. K. A1 - Shoorijeh, S. J. A1 - Tarditi, C. R. A1 - Waly, N. E. A1 - Wictum, E. J. A1 - Lyons, L. A. T1 - Feline non-repetitive mitochondrial DNA control region database for forensic evidence JF - Forensic science international : an international journal dedicated to the applications of genetics in the administration of justice ; Genetics N2 - The domestic cat is the one of the most popular pets throughout the world. A by-product of owning, interacting with, or being in a household with a cat is the transfer of shed fur to clothing or personal objects. As trace evidence, transferred cat fur is a relatively untapped resource for forensic scientists. Both phenotypic and genotypic characteristics can be obtained from cat fur, but databases for neither aspect exist. Because cats incessantly groom, cat fur may have nucleated cells, not only in the hair bulb, but also as epithelial cells on the hair shaft deposited during the grooming process, thereby generally providing material for DNA profiling. To effectively exploit cat hair as a resource, representative databases must be established. The current study evaluates 402 bp of the mtDNA control region (CR) from 1394 cats, including cats from 25 distinct worldwide populations and 26 breeds. Eighty-three percent of the cats are represented by 12 major mitotypes. An additional 8.0% are clearly derived from the major mitotypes. Unique sequences are found in 7.5% of the cats. The overall genetic diversity for this data set is 0.8813 +/- 0.0046 with a random match probability of 11.8%. This region of the cat mtDNA has discriminatory power suitable for forensic application worldwide. KW - Forensic science KW - Domestic cat KW - mtDNA KW - Mitochondria KW - d-Loop KW - Control region Y1 - 2011 U6 - https://doi.org/10.1016/j.fsigen.2010.01.013 SN - 1872-4973 VL - 5 IS - 1 SP - 33 EP - 42 PB - Elsevier CY - Clare ER - TY - GEN A1 - Bäumer, Wolfgang A1 - Rossbach, Kristine A1 - Mischke, Reinhard A1 - Reines, Ilka A1 - Langbein-Detsch, Ines A1 - Lüth, Anja A1 - Kleuser, Burkhard T1 - Decreased concentration and enhanced metabolism of sphingosine-1-Phosphate in lesional skin of dogs with atopic dermatitis disturbed Sphingosine-1-Phosphate homeostasis in atopic Dermatitis T2 - The journal of investigative dermatology Y1 - 2011 U6 - https://doi.org/10.1038/jid.2010.252 SN - 0022-202X VL - 131 IS - 1 SP - 266 EP - 268 PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Müller, Carsten A1 - Ullmann, Kristina A1 - Steinberg, Pablo T1 - The grapevine-shoot extract Vineatrol30 Inhibits the chemically induced malignant transformation of BALB/c-3T3 Cells JF - Journal of medicinal food N2 - Vineatrol (R) 30 (developed and produced jointly by Breko GmbH [Bremen, Germany] and Actichem [Montauban, France]) is a grapevine-shoot extract that contains resveratrol as well as considerable amounts of resveratrol oligomers. In the present study it is shown that Vineatrol30 at a noncytotoxic concentration of 2.3 mu g/mL significantly reduced the number of malignantly transformed foci induced by a sequential treatment of BALB/c-3T3 cells with 3-methylcholanthrene and 12-O-tetradecanoylphorbol 13-acetate in the so-called BALB/c-3T3 cell transformation assay. At a higher concentration Vineatrol30 drastically decreased the relative plating efficiency of the cells. Furthermore, the results suggest that the resveratrol oligomers present in Vineatrol30, independently from resveratrol itself, were indeed able to inhibit the formation of malignantly transformed BALB/c-3T3 foci. KW - BALB/c-3T3 cells KW - cell transformation assay KW - resveratrol KW - resveratrol oligomers KW - Vineatrol (R) 30 Y1 - 2011 U6 - https://doi.org/10.1089/jmf.2010.0022 SN - 1096-620X VL - 14 IS - 1-2 SP - 34 EP - 39 PB - Liebert CY - New Rochelle ER - TY - JOUR A1 - Chaykovska, Lyubov A1 - Tsuprykov, Oleg A1 - Hocher, Berthold T1 - Biomarkers for the prediction of mortality and morbidity in patients with renal replacement therapy JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - The mortality of end-stage renal disease (ESRD) patients on dialysis remains high despite great improvement of dialysis technologies in the past decades. These patients die due to infectious diseases (mainly sepsis), cardiovascular diseases such as myocardial infarction, heart failure, stroke, and, in particular, sudden cardiac death. End stage renal disease is a complex condition, where the failure of kidney function is accompanied by numerous metabolic changes affecting almost all organ systems of the human body. Many of the biomarker characteristics of the individually affected organ systems have been associated with adverse outcomes. These biomarkers are different in patients with ESRD compared to the general population in the prediction of morbidity and mortality. Biomarker research in this field should aim to identify patients at risk for the different disease entities. Traditional biomarkers such as CRP, BNP, and troponins as well as new biomarkers such as fetuin, CD 154, and relaxin were analyzed in patients on dialysis. We will include observational as well as prospective clinical trials in this review. Furthermore, we will also discuss proteomics biomarker studies. The article assess the potential diagnostic value of different biomarkers in daily clinical practice as well as their usefulness for clinical drug development in end stage renal disease patients. Y1 - 2011 SN - 1433-6510 VL - 57 IS - 7-8 SP - 455 EP - 467 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Sharkovska, Yuliya A1 - Kalk, Philipp A1 - von Websky, Karoline A1 - Relle, Katharina A1 - Pfab, Thiemo A1 - Alter, Markus L. A1 - Fischer, Yvan A1 - Hocher, Berthold T1 - Renoprotective effects of combined endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 in acute and chronic experimental renal damage JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Acute kidney injury (AKI) as well as chronic renal failure are associated with a huge mortality/morbidity. However, so far no drugs have been approved for the treatment of acute kidney failure and only a few for the treatment of chronic kidney disease (CKD). We analysed the effect of SLV 338, a neutral endopeptidase (NEP)/endothelin converting enzyme (ECE)-inhibitor in animal models of acute kidney failure as well as chronic renal failure. Methods: Acute renal failure was induced in male Wistar rats by uninephrectomy and clamping of the remaining kidney for 55 minutes. SLV338 (total dose: 4.9 mg/kg) or vehicle was continuously infused for 2 hours (starting 20 minutes prior to clamping). Sham operated animals served as controls. Plasma creatinine was measured at baseline and day 2 and 8 after renal ischemia-reperfusion. Hypertensive renal damage was induced in male Sprague Dawley rats by nitric oxide deficiency using L-NAME (50 mg/kg per day, added to drinking water for 4 weeks). One group was treated over the same time period with SLV338 (30 mg/kg per day, mixed with food). Systolic blood pressure was monitored weekly. At study end, urine and blood samples were collected and kidneys were harvested. Results: Acute renal ischemia-reperfusion caused a 5-fold plasma creatinine elevation (day 2), which was significantly attenuated by more than 50 % in animals treated with SLV338 (p < 0.05). Renal failure was accompanied by a 67 % mortality in vehicle-treated rats, but only 20 % after SLV338 treatment (p = 0.03 compared to sham controls). Chronic L-NAME administration caused hypertension, urinary albumin excretion, glomerulosclerosis, renal arterial remodelling, and renal interstitial fibrosis. Treatment with SLV338 did not significantly affect blood pressure, but abolished renal tissue damage (interstitial fibrosis, glomerulosclerosis, renal arterial remodelling (p < 0.05 versus L-NAME group in each case). Conclusions: The dual ECE/NEP inhibitor SLV338 preserves kidney function and reduces mortality in severe acute ischemic renal failure. Moreover, combined ECE/NEP inhibition prevents hypertensive renal tissue damage in a blood pressure independent manner in L-NAME-treated rats. KW - Renal failure KW - endothelin-converting enzyme KW - neutral endopeptidase Y1 - 2011 SN - 1433-6510 VL - 57 IS - 7-8 SP - 507 EP - 515 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Hocher, Berthold A1 - Heimerl, Dirk A1 - Slowinski, Torsten A1 - Godes, Michael A1 - Halle, Horst A1 - Priem, Friedrich A1 - Pfab, Thiemo T1 - Birthweight and Fetal Glycosylated Hemoglobin at Birth in Newborns Carrying the GLUT1 XbaI Gene Polymorphism JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Low birthweight is an independent risk factor of glucose intolerance and type 2 diabetes in later life. Genetically determined insulin resistance and subsequently impaired glucose uptake might explain both reduced fetal growth and elevated blood glucose. The glucose transporter 1 (GLUT!) plays an important role for fetal glucose uptake as well as for maternal-fetal glucose transfer, and it has been associated with insulin resistance in adults. The present study hypothesized that the common fetal GLUT1 XbaI polymorphism might reduce fetal insulin sensitivity and/or glucose supply in utero, thus affecting fetal blood glucose and fetal growth. Methods: A genetic association study was conducted at the obstetrics department of the Charite University Hospital, Berlin, Germany. 119.1 white women were included after delivery, and all newborns were genotyped for the GLUT1 XbaI polymorphism. Total glycosylated hemoglobin was quantified, serving as a surrogate of glycemia during the last weeks of pregnancy. Results: The analysis of this large population showed no significant differences in fetal glycosylated hemoglobin or birthweight for the different fetal GLUT1 XbaI genotypes. Only newborns carrying the mutated allele show the previously published inverse association between birthweight and glycosylated hemoglobin. Conclusions: The results suggest that there is no prenatal effect of the fetal GLUT1 XbaI polymorphism on fetal insulin sensitivity, intrauterine fetal glucose supply or fetal growth. However, the polymorphism seems to modulate the inverse interaction between birthweight and fetal glycemia. KW - GLUT1 XbaI gene polymorphism KW - birthweight KW - total glycosylated hemoglobin KW - insulin resistance KW - fetal programming Y1 - 2011 SN - 1433-6510 VL - 57 IS - 9-10 SP - 651 EP - 657 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Henze, Andrea A1 - Aumer, Franziska A1 - Grabner, Arthur A1 - Raila, Jens A1 - Schweigert, Florian J. T1 - Genetic differences in the serum proteome of horses, donkeys and mules are detectable by protein profiling JF - The British journal of nutrition : an international journal devoted to the science of human and animal nutrition N2 - Although horses and donkeys belong to the same genus, their genetic characteristics probably result in specific proteomes and post-translational modifications (PTM) of proteins. Since PTM can alter protein properties, specific PTM may contribute to species-specific characteristics. Therefore, the aim of the present study was to analyse differences in serum protein profiles of horses and donkeys as well as mules, which combine the genetic backgrounds of both species. Additionally, changes in PTM of the protein transthyretin (TTR) were analysed. Serum protein profiles of each species (five animals per species) were determined using strong anion exchanger ProteinChips (R) (Bio-Rad, Munich, Germany) in combination with surface-enhanced laser desorption ionisation-time of flight MS. The PTM of TTR were analysed subsequently by immunoprecipitation in combination with matrix-assisted laser desorption ionisation-time of flight MS. Protein profiling revealed species-specific differences in the proteome, with some protein peaks present in all three species as well as protein peaks that were unique for donkeys and mules, horses and mules or for horses alone. The molecular weight of TTR of horses and donkeys differed by 30Da, and both species revealed several modified forms of TTR besides the native form. The mass spectra of mules represented a merging of TTR spectra of horses and donkeys. In summary, the present study indicated that there are substantial differences in the proteome of horses and donkeys. Additionally, the results probably indicate that the proteome of mules reveal a higher similarity to donkeys than to horses. KW - Mass spectrometry KW - Post-translational modifications KW - Proteome KW - Species differences Y1 - 2011 U6 - https://doi.org/10.1017/S0007114511000845 SN - 0007-1145 VL - 106 SP - S170 EP - S173 PB - Cambridge Univ. Press CY - Cambridge ER - TY - JOUR A1 - Raila, Jens A1 - Rohn, Sascha A1 - Schweigert, Florian J. A1 - Abraham, Getu T1 - Increased antioxidant capacity in the plasma of dogs after a single oral dosage of tocotrienols JF - The British journal of nutrition : an international journal devoted to the science of human and animal nutrition N2 - The intestinal absorption of tocotrienols (TCT) in dogs is, to our knowledge, so far unknown. Adult Beagle dogs (n 8) were administered a single oral dosage of a TCT-rich fraction (TRF; 40 mg/kg body weight) containing 32% alpha-TCT, 2% beta-TCT, 27% gamma-TCT, 14% delta-TCT and 25% alpha-tocopherol (alpha-TCP). Blood was sampled at baseline (fasted), 1, 2, 3, 4, 5, 6, 8 and 12 h after supplementation. Plasma and chylomicron concentrations of TCT and alpha-TCP were measured at each time point. Plasma TAG were measured enzymatically, and plasma antioxidant capacity was assessed by the Trolox equivalent antioxidant capacity assay. In fasted dogs, levels of TCT were 0.07 (SD 0.03) mu mol/l. Following the administration of the TRF, total plasma TCT peaked at 2 h (7.16 (SD 3.88) mu mol/l; P<0.01) and remained above baseline levels (0.67 (SD 0.44) mu mol/l; P, 0.01) at 12 h. The TCT response in chylomicrons paralleled the increase in TCT in plasma with a maximum peak (3.49 (SD 2.06) mu mol/l; P, 0.01) at 2 h post-dosage. alpha-TCP was the major vitamin E detected in plasma and unaffected by TRF supplementation. The Trolox equivalent values increased from 2 h (776 (SD 51.2) mu mol/l) to a maximum at 12 h (1130 (SD 7.72) mmol/l; P<0.01). The results show that TCT are detected in postprandial plasma of dogs. The increase in antioxidant capacity suggests a potential beneficial role of TCT supplementation in the prevention or treatment of several diseases in dogs. KW - Dogs KW - Tocotrienols KW - Intestinal absorption KW - Antioxidant capacity Y1 - 2011 U6 - https://doi.org/10.1017/S0007114511000511 SN - 0007-1145 VL - 106 IS - 7 SP - S116 EP - S119 PB - Cambridge Univ. Press CY - Cambridge ER - TY - JOUR A1 - Müller, Kerstin E. A1 - Altenkamp, Rainer A1 - Raila, Jens A1 - Schmidt, Daniel A1 - Dietrich, Robert A1 - Hurtienne, Andrea A1 - Wink, Michael A1 - Krone, Oliver A1 - Brunnberg, Leo A1 - Schweigert, Florian J. T1 - Plasma concentration of alpha-tocopherol in different free-ranging birds of prey JF - European journal of wildlife research N2 - In this study, we investigated the alpha-tocopherol plasma concentrations in healthy free-ranging nestlings of the white-tailed sea eagle (Haliaeetus albicilla) (n=32), osprey (Pandion haliaetus) (n=39), northern goshawk (Accipiter gentilis) (n=25), common buzzard (Buteo buteo) (n=31), and honey buzzard (Pernis apivorus) (n=18) as well as of free-ranging adults of the white-tailed sea eagle (n=10), osprey (n=31), and northern goshawk (n=45). alpha-Tocopherol plasma concentrations were determined by reverse-phase high-performance liquid chromatography. alpha-Tocopherol plasma concentrations in nestlings of osprey, white-tailed sea eagle, and northern goshawk did not differ significantly amongst the species, but the common buzzard and honey buzzard nestlings had significantly lower alpha-tocopherol plasma concentrations than nestlings of the other species (both P<0.001). Adult male ospreys and white-tailed sea eagles had significantly higher alpha-tocopherol concentrations compared to adult females (both P<0.005). Adult ospreys and northern goshawks had significantly higher alpha-tocopherol plasma concentrations compared to their nestlings (both P<0.001). In adult female northern goshawks, plasma concentrations of alpha-tocopherol increased significantly before egg laying (P<0.001). These results demonstrate alpha-tocopherol plasma concentrations in birds of prey to be species specific and influenced by age and reproductive status. KW - alpha-Tocopherol KW - Birds of prey KW - Plasma concentration Y1 - 2011 U6 - https://doi.org/10.1007/s10344-011-0516-z SN - 1612-4642 VL - 57 IS - 5 SP - 1043 EP - 1049 PB - Springer CY - New York ER - TY - JOUR A1 - Chupeerach, Chaowanee A1 - Harnroongroj, Talabporn A1 - Phonrat, Benjaluck A1 - Tungtrongchitr, Anchalee A1 - Schweigert, Florian J. A1 - Tungtrongchitr, Rungsunn A1 - Preutthipan, Sangchai T1 - Decreased retinol transport proteins in thai post-menopausal women with Osteporosis JF - The Southeast Asian journal of tropical medicine and public health : official publication of the SEAMEO Regional Tropical Medicine and Public Health Project (TROPMED) N2 - High vitamin A ingestion or high serum retinol have been postulated to increase the risk of fractures and osteoporosis by reduced bone mineral density (BMD). Retinol is carried and transported to the tissues bound to retinol binding protein 4 (RBP4) and transthyretin (TTR). The relationships between retinol, retinol transport protein, retinol binding protein 4 (RBP4) and transthyretin (TTR) and BMD and osteoporosis are unclear. To examine the association between retinol and RBP4 and TTR and osteoporosis, 73 osteoporotic and 71 normal Thai postmenopausal women were studied. RBP4 and retinol levels did not differ between the groups. Serum TTR was significantly higher in control than osteoporotic subjects (89.47 and 144.53 mu g/ml, respectively, p=0.003, Mann-Whitney U test). TTR was positively correlated with BMD at several sites, such as the total radius bone (r=0.172, p=0.008, Spearman rank test). Osteoporosis risk was analyzed with binary logistic regression. Lean elderly Thais with lower TTR levels had a higher risk of osteoporosis. RBP4 and retinol levels had no relationship with disease status among Thai post-menopausal women. These results suggest calcium, minerals, vitamins and the retinol transport protein, transthyretin may be involved in the pathogenesis of osteoporosis. KW - transthyretin KW - vitamin A KW - retinol binding protein 4 KW - post-menopausal Thai women Y1 - 2011 SN - 0125-1562 VL - 42 IS - 6 SP - 1515 EP - 1520 PB - SEAMEO CY - Bangkok ER - TY - JOUR A1 - Eggert, Kai A1 - Rawel, Harshadrai Manilal A1 - Pawelzik, Elke T1 - In vitro degradation of wheat gluten fractions by Fusarium graminearum proteases JF - European food research and technology : official organ of the EuCheMS, Division of Food Chemistry N2 - Fusarium spp. infection of cereal grain is a common problem, which leads to a dramatic loss of grain quality. The aim of the present study was to investigate the effect of Fusarium infection on the wheat storage protein gluten and its fractions, the gliadins and glutenins, in an in vitro model system. Gluten proteins were digested by F. graminearum proteases for 2, 4, 8 and 24 h, separated by Osborne fractionation and characterised by chromatographic (RP-HPLC) and electrophoretic analysis (SDS-Page). Gluten digestion by F. graminearum proteases showed in comparison with gliadins a preference for the glutenins whereas the HMW subfraction was at most affected. In comparison with a untreated control, the HMW subfraction was degraded of about 97% after 4 h incubation with Fusarium proteases. Separate digestion of gliadin and glutenin underlined the preference for HMW-GS. Analogue to the observed change in the gluten composition, the yield of the proteins extracted changed. A higher amount of glutenin fragments was found in the gliadin extraction solution after digestion and could mask a gliadin destruction at the same time. This observation can contribute to explain the frequently reported reduced glutenin amount parallel to an increase in gliadin quantity after Fusarium infection in grains. KW - Gluten KW - Gliadin and glutenin fractions KW - Peptides KW - Serine and trypsin protease Y1 - 2011 U6 - https://doi.org/10.1007/s00217-011-1566-x SN - 1438-2377 VL - 233 IS - 4 SP - 697 EP - 705 PB - Springer CY - New York ER - TY - CHAP A1 - Khalil, Mahomound A1 - Isalm, K. Shaiful A1 - Raila, Jens A1 - Schenk, R. A1 - Rawel, Harshadrai Manilal A1 - Schweigert, Florian J. T1 - Content of lutein and lutein ester in tagetes and improvement of their stability T2 - Annals of nutrition & metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS) KW - lutein ester KW - Emulsion KW - MCT oil KW - Stability KW - UV light Y1 - 2011 SN - 0250-6807 VL - 58 IS - 3 SP - 16 EP - 16 PB - Karger CY - Basel ER - TY - JOUR A1 - Zebger-Gong, Hong A1 - Mueller, Dominik A1 - Diercke, Michaela A1 - Haffner, Dieter A1 - Hocher, Berthold A1 - Verberckmoes, Steven A1 - Schmidt, Sven A1 - D'Haese, Patrick C. A1 - Querfeld, Uwe T1 - 1,25-Dihydroxyvitamin D-3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix JF - Journal of hypertension N2 - Background and objective Whether treatment with vitamin D receptor activators contributes to cardiovascular disease in patients with chronic kidney disease is a matter of debate. We studied mechanisms involved in vitamin D-related vascular calcifications in vivo and in vitro. Methods Aortic calcifications were induced in subtotally nephrectomized (SNX) rats by treatment with a high dose (0.25 mu g/kg per day) of 1,25-dihydroxyvitamin D-3 (calcitriol) given for 6 weeks. Likewise, primary rat vascular smooth muscle cells (VSMCs) were incubated with calcitriol at concentrations ranging from 10(-11) to 10(-7) mol/l. Immunohistochemistry revealed that the aortic expression of osteopontin, osteocalcin and bone sialoprotein was significantly increased in calcitriol-treated SNX rats compared to untreated SNX controls. In addition, aortic expression of the transient receptor potential vanilloid calcium channel 6 (TRPV6) and calbindin D9k was significantly up-regulated by treatment with calcitriol. Furthermore, calcitriol significantly increased expression of the osteogenic transcription factor osterix. In-vitro studies showed similar results, confirming that these effects could be attributed to treatment with calcitriol. Conclusions High-dose calcitriol treatment induces an osteoblastic phenotype in VSMC both in SNX rats and in vitro, associated with up-regulation of proteins regulating mineralization and calcium transport, and of the osteogenic transcription factor osterix. KW - calbindin D9k KW - calcitriol KW - calcium transport KW - osteoblast KW - osterix KW - TRPV5 KW - TRPV6 KW - vascular calcification Y1 - 2011 U6 - https://doi.org/10.1097/HJH.0b013e328340aa30 SN - 0263-6352 VL - 29 IS - 2 SP - 339 EP - 348 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - CHAP A1 - Geschka, Sandra A1 - Kretschmer, A. A1 - Sharkovska, J. A1 - Evgenov, O. V. A1 - Lawrenz, Bettina A1 - Stasch, Johannes-Peter A1 - Hocher, Berthold T1 - Soluble guanylate cyclase stimulation prevents fibrotic tissue Remodelling and improves survival in salt-sensitive dahl rats T2 - Journal of vascular research Y1 - 2011 SN - 1018-1172 VL - 48 IS - 4 SP - 171 EP - 171 PB - Karger CY - Basel ER - TY - THES A1 - Riedel, Katja T1 - Elucidation of the epithelial sodium channel as a salt taste receptor candidate and search for novel salt taste receptor candidates T1 - Validierung des epithelialen Natriumkanals als Salzgeschmacksrezeptor und Suche nach unbekannten menschlichen Salzgeschmacksrezeptoren N2 - Salty taste has evolved to maintain electrolyte homeostasis, serving as a detector for salt containing food. In rodents, salty taste involves at least two transduction mechanisms. One is sensitive to the drug amiloride and specific for Na+, involving epithelial sodium channel (ENaC). A second rodent transduction pathway, which is triggered by various cations, is amiloride insensitive and not almost understood to date. Studies in primates showed amiloride-sensitive as well as amiloride-insensitive gustatory responses to NaCl, implying a role of both salt taste transduction pathways in humans. However, sensory studies in humans point to largely amiloride-insensitive sodium taste perception. An involvement of ENaC in human sodium taste perception was not shown, so far. In this study, ENaC subunit protein and mRNA could be localized to human taste bud cells (TBC). Thus, basolateral αβγ-ENaC ion channels are likely in TBC of circumvallate papillae, possibly mediating basolateral sodium entry. Similarly, basolateral βγ-ENaC might play a role in fungiform TBC. Strikingly, δ-ENaC subunit was confined to taste bud pores of both papillae, likely mediating gustatory sodium entry in TBC, either apical or paracellular via tight junctions. However, regional separation of δ-ENaC and βγ-ENaC in fungiform and circumvallate TBC indicate the presence of unknown interaction partner necessary to assemble into functional ion channels. However, screening of a macaque taste tissue cDNA library did neither reveal polypeptides assembling into a functional cation channel by interaction with δ-ENaC or βγ-ENaC nor ENaC independent salt taste receptor candidates. Thus, ENaC subunits are likely involved in human taste transduction, while exact composition and identity of an amiloride (in)sensitive salt taste receptors remain unclear. Localization of δ-ENaC in human taste pores strongly suggests a role in human taste transduction. In contrast, δ-ENaC is classified as pseudogene Scnn1d in mouse. However, no experimental detected sequences are annotated, while evidences for parts of Scnn1d derived mRNAs exist. In order to elucidate if Scnn1d is possibly involved in rodent salt taste perception, Scnn1d was evaluated in this study to clarify if Scnn1d is a gene or a transcribed pseudogene in mice. Comparative mapping of human SCNN1D to mouse chromosome 4 revealed complete Scnn1d sequence as well as its pseudogenization by Mus specific endogenous retroviruses. Moreover, tissue specific transcription of unitary Scnn1d pseudogene was found in mouse vallate papillae, kidney and testis and led to identification of nine Scnn1d transcripts. In vitro translation experiments showed that Scnn1d transcripts are coding competent for short polypeptides, possibly present in vivo. However, no sodium channel like function or sodium channel modulating activity was evident for Scnn1d transcripts and/or derived polypeptides. Thus, an involvement of mouse δ-ENaC in sodium taste transduction is unlikely and points to species specific differences in salt taste transduction mechanisms. N2 - Der Salzgeschmack ermöglicht elektrolytreiche Nahrungsquellen zu erkennen und ist eine essentielle Komponente für den Erhalt des Elektrolythaushalts. In Nagern sind bisher zwei Mechanismen bekannt, welche an der Vermittlung des Salzgeschmacks beteiligt sind. Ein Natrium-spezifischer, Amilorid-sensitiver Signaltransduktionsweg wird über den epithelialen Natriumkanal (ENaC) vermittelt. Ein weiterer, bisher ungeklärter Transduktionsweg, ist Amilorid-unempfindlich und wird durch verschiedene Kationen vermittelt. Studien in Primaten konnten Amilorid-sensitive als auch -insensitive gustatorische Signaltransduktionswege nachweisen, wohingegen sensorische Studien auf eine Amilorid-Unempfindlichkeit des Natrium-spezifischen humanen Salzgeschmacks hinweisen. Eine Beteiligung des ENaC bei der Vermittlung des menschlichen Salzgeschmacks wurde bislang nicht gezeigt. In dieser Arbeit konnte die mRNA als auch Proteine von ENaC Untereineiten in menschlichen Geschmacksrezeptorzellen (GRZ) lokalisiert werden. Demzufolge, sind αβγ-ENaC Ionenkanäle möglicherweise an einem basolateralen Natriumeinstrom in circumvallaten GRZ beteiligt. Die basolaterale Lokalisation von βγ-ENaC in fungiformen GRZ weißt auf eine gleichartige Funktion hin. Die außergewöhnliche Lokalisation der δ-ENaC Untereineit ausschließlich in der Porenregion von Geschmacksknospen beider Geschmackspapillen, legt eine Beteiligung dieser ENaC Untereinheit bei der Vermittlung geschmacksrelevanter apikaler bzw. transzellulärer Natriumströme nahe. Gleichwohl weist die räumliche Trennung von apikalen δ-ENaC und basolateralen βγ-ENaC auf die Existenz unbekannter Interaktionspartner hin, da beide getrennt voneinander nicht in der Lage sind effektive Natriumkanäle zu assemblieren. Die Durchmusterung einer geschmacksrelevanten cDNA Bibliothek führte weder zur Identifikation von ENaC Interaktionspartnern, noch von ENaC unabhängigen Polypeptiden, welche in der Lage sind einen Kationenkanal zu bilden. Die genaue Zusammensetzung humaner Amilorid- (in)sensitiver Salzrezeptoren bleibt daher unklar und ein spannendes Feld. Der Nachweis von ENaC in humanen GRZ und insbesondere die Poren assoziierte Lokalisation der δ-ENaC Untereinheit impliziert eine wichtige Rolle bei der gustatorischen Signaltransduktion. Erstaunlicherweise ist die orthologe δ-ENaC Untereinheit der Maus als Scnn1d Pseudogen klassifiziert. Neben dieser automatischen Annotierung sind keine experimentell ermittelten Sequenzen in Datenbanken hinterlegt obwohl Scnn1d abgeleitete mRNA nachgewiesen werden konnte. Im Rahmen dieser Arbeit wurde untersucht ob Scnn1d ein Gen oder ein transkribiertes Pseudogen ist, um eine mögliche Rolle bei der Transduktion des murinen Salzgeschmacks zu klären. Durch Sequenzabgleich mit humanen SCNN1D konnte das vollständige Scnn1d Gen auf dem Chromosom 4 der Maus identifiziert werden, wobei sich dessen Pseudogenisierung durch Mus spezifische endogene Retroviren zeigte. Darüber hinaus wurden neun gewebsspezifische Scnn1d Transkripte nachgewiesen, welche für kurze Polypeptide kodieren. Eine mögliche Funktion derselben als Ionenkanal bzw. eine modulatorische Funktion konnte nicht gezeigt werden. Eine Beteiligung des pseudogenisierten δ-ENaC an der Vermittlung des Salzgeschmacks der Maus ist daher unwahrscheinlich und deutet auf Speziesunterschiede der Salzgeschmacksvermittlung hin. KW - ENaC KW - Salzgeschmack KW - ENaC KW - salt taste perception Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-58764 ER - TY - JOUR A1 - Carlsohn, Anja A1 - Scharhag-Rosenberger, Friederike A1 - Cassel, Michael A1 - Mayer, Frank T1 - Resting metabolic rate in elite rowers and canoeists difference between indirect calorimetry and prediction JF - Annals of nutrition & metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS) N2 - Background: Athletes may differ in their resting metabolic rate (RMR) from the general population. However, to estimate the RMR in athletes, prediction equations that have not been validated in athletes are often used. The purpose of this study was therefore to verify the applicability of commonly used RMR predictions for use in athletes. Methods: The RMR was measured by indirect calorimetry in 17 highly trained rowers and canoeists of the German national teams (BMI 24 +/- 2 kg/m(2), fat-free mass 69 +/- 15 kg). In addition, the RMR was predicted using Cunningham (CUN) and Harris-Benedict (HB) equations. A two-way repeated measures ANOVA was calculated to test for differences between predicted and measured RMR (alpha = 0.05). The root mean square percentage error (RMSPE) was calculated and the Bland-Altman procedure was used to quantify the bias for each prediction. Results: Prediction equations significantly underestimated the RMR in males (p < 0.001). The RMSPE was calculated to be 18.4% (CUN) and 20.9% (HB) in the entire group. The bias was 133 kcal/24 h for CUN and 202 kcal/24 h for HB. Conclusions: Predictions significantly underestimate the RMR in male heavyweight endurance athletes but not in females. In athletes with a high fat-free mass, prediction equations might therefore not be applicable to estimate energy requirements. Instead, measurement of the resting energy expenditure or specific prediction equations might be needed for the individual heavyweight athlete. KW - Energy requirement KW - Calorimetry KW - Fat-free mass KW - Nutritional counseling KW - Athletes Y1 - 2011 U6 - https://doi.org/10.1159/000330119 SN - 0250-6807 VL - 58 IS - 3 SP - 239 EP - 244 PB - Karger CY - Basel ER -