TY  - JOUR
A1  - Danquah, Ina
A1  - Dobrucky, C. Lydia
A1  - Frank, Laura K.
A1  - Henze, Andrea
A1  - Amoako, Yaw A.
A1  - Bedu-Addo, George
A1  - Raila, Jens
A1  - Schulze, Matthias Bernd
A1  - Mockenhaupt, Frank P.
A1  - Schweigert, Florian J.
T1  - Vitamin A: potential misclassification of vitamin A status among patients with type 2 diabetes and hypertension in urban Ghana
JF  - The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.
N2  - Background: Sub-Saharan Africa is facing a double burden of malnutrition: vitamin A deficiency (VAD) prevails, whereas the nutrition-related chronic conditions type 2 diabetes (T2D) and hypertension are emerging. Serum retinol a VAD marker increases in kidney disease and decreases in inflammation, which can partly be attributed to alterations in the vitamin A transport proteins retinol-binding protein 4 (RBP4) and prealbumin. Kidney dysfunction and inflammation commonly accompany T2D and hypertension.
 Objective: Among urban Ghanaians, we investigated the associations of T2D and hypertension with serum retinol as well as the importance of kidney function and inflammation in this regard.
 Design: A hospital-based, case-control study in individuals for risk factors of T2D, hypertension, or both was conducted in Kumasi, Ghana (328 controls, 197 with T2D, 354 with hypertension, and 340 with T2D plus hypertension). In 1219 blood samples, serum retinol, RBP4, and prealbumin were measured. Urinary albumin and estimated glomerular filtration rate (eGFR) defined kidney function. C-reactive protein (CRP) >5 mg/L indicated inflammation. We identified associations of T2D and hypertension with retinol by linear regression and calculated the contribution of RBP4, prealbumin, urinary albumin, eGFR, and CRP to these associations as the percentages of the explained variance of retinol.
 Results: VAD (retinol <1.05 mu mol/L) was present in 10% of this predominantly female, middle-aged, overweight, and deprived population. Hypertension, but not T2D, was positively associated with retinol (beta: 0.12; 95% CI: 0.08, 0,17), adjusted for age, sex, socioeconomic factors, anthropometric measurements, and lifestyle. In addition to RBP4 (72%) and prealbumin (22%), the effect of increased retinol on individuals with hypertension was mainly attributed to impaired kidney function (eGFR: 30%; urinary albumin: 5%) but not to inflammation.
 Conclusions: In patients with hypertension, VAD might be underestimated because of increased serum retinol in the context of kidney dysfunction. Thus, the interpretation of serum retinol in sub-Saharan Africa should account for hypertension status.
KW  - hypertension
KW  - inflammation
KW  - kidney dysfunction
KW  - type 2 diabetes
KW  - vitamin A deficiency
Y1  - 2015
U6  - https://doi.org/10.3945/ajcn.114.101345
SN  - 0002-9165
SN  - 1938-3207
VL  - 102
IS  - 1
SP  - 207
EP  - 214
PB  - American Society for Nutrition, Inc.
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Luckert, Claudia
A1  - Hessel, Stefanie
A1  - Lampen, Alfonso
A1  - Braeuning, Albert
T1  - Utility of an appropriate reporter assay: Heliotrine interferes with GAL4/upstream activation sequence-driven reporter gene systems
JF  - Analytical biochemistry : methods in the biological sciences
N2  - Reporter gene assays are widely used for the assessment of transcription factor activation following xenobiotic exposure of cells. A critical issue with such assays is the possibility of interference of test compounds with the test system, for example, by direct inhibition of the reporter enzyme. Here we show that the pyrrolizidine alkaloid heliotrine interferes with reporter signals derived from GAL4-based nuclear receptor transactivation assays by a mechanism independent of luciferase enzyme inhibition. These data highlight the necessity to conduct proper control experiments in order to avoid perturbation of reporter assays by test chemicals. (C) 2015 Elsevier Inc. All rights reserved.
KW  - Firefly luciferase inhibition
KW  - Nuclear receptor
KW  - Transactivation assay
Y1  - 2015
U6  - https://doi.org/10.1016/j.ab.2015.07.009
SN  - 0003-2697
SN  - 1096-0309
VL  - 487
SP  - 45
EP  - 48
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - GEN
A1  - Kumar, Kevin K.
A1  - Goodwin, Cody R.
A1  - Uhouse, Michael A.
A1  - Bornhorst, Julia
A1  - Schwerdtle, Tanja
A1  - Aschner, Michael A.
A1  - McLean, John A.
A1  - Bowman, Aaron B.
T1  - Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status
N2  - Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 232 
KW  - cells
KW  - coenzyme-a
KW  - database
KW  - energy-metabolism
KW  - glutathione
KW  - hallervorden-spatz-syndrome
KW  - mobility-mass spectrometry
KW  - model
KW  - neurodegeneration
KW  - neurotoxicity
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-94314
SP  - 363
EP  - 370
ER  - 
TY  - JOUR
A1  - Kumar, Kevin K.
A1  - Goodwin, Cody R.
A1  - Uhouse, Michael A.
A1  - Bornhorst, Julia
A1  - Schwerdtle, Tanja
A1  - Aschner, Michael A.
A1  - McLean, John A.
A1  - Bowman, Aaron B.
T1  - Untargeted metabolic profiling identifies interactions between Huntington's disease and neuronal manganese status
JF  - Metallomics
N2  - Manganese (Mn) is an essential micronutrient for development and function of the nervous system. Deficiencies in Mn transport have been implicated in the pathogenesis of Huntington's disease (HD), an autosomal dominant neurodegenerative disorder characterized by loss of medium spiny neurons of the striatum. Brain Mn levels are highest in striatum and other basal ganglia structures, the most sensitive brain regions to Mn neurotoxicity. Mouse models of HD exhibit decreased striatal Mn accumulation and HD striatal neuron models are resistant to Mn cytotoxicity. We hypothesized that the observed modulation of Mn cellular transport is associated with compensatory metabolic responses to HD pathology. Here we use an untargeted metabolomics approach by performing ultraperformance liquid chromatography-ion mobility-mass spectrometry (UPLC-IM-MS) on control and HD immortalized mouse striatal neurons to identify metabolic disruptions under three Mn exposure conditions, low (vehicle), moderate (non-cytotoxic) and high (cytotoxic). Our analysis revealed lower metabolite levels of pantothenic acid, and glutathione (GSH) in HD striatal cells relative to control cells. HD striatal cells also exhibited lower abundance and impaired induction of isobutyryl carnitine in response to increasing Mn exposure. In addition, we observed induction of metabolites in the pentose shunt pathway in HD striatal cells after high Mn exposure. These findings provide metabolic evidence of an interaction between the HD genotype and biologically relevant levels of Mn in a striatal cell model with known HD by Mn exposure interactions. The metabolic phenotypes detected support existing hypotheses that changes in energetic processes underlie the pathobiology of both HD and Mn neurotoxicity.
KW  - hallervorden-spatz-syndrome
KW  - mobility-mass spectrometry
KW  - energy-metabolism
KW  - coenzyme-a
KW  - model
KW  - neurotoxicity
KW  - glutathione
KW  - database
KW  - cells
KW  - neurodegeneration
Y1  - 2015
U6  - https://doi.org/10.1039/C4MT00223G
SN  - 1756-591X
SN  - 1756-5901
VL  - 7
SP  - 363
EP  - 370
PB  - RSC Publ.
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Kumar, Kevin K.
A1  - Goodwin, Cody R.
A1  - Uhouse, Michael A.
A1  - Bornhorst, Julia
A1  - Schwerdtle, Tanja
A1  - Aschner, Michael A.
A1  - McLean, John A.
A1  - Bowman, Aaron B.
T1  - Untargeted metabolic profiling identifies interactions between
JF  - Metallomics : integrated biometal science
Y1  - 2015
U6  - https://doi.org/10.1039/c4mt00223g
SN  - 1756-5901
SN  - 1756-591X
VL  - 7
IS  - 2
SP  - 363
EP  - 370
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - THES
A1  - Vossenkuhl, Birgit
T1  - Transmission of MRSA along the meat supply chain
BT  - A methodological concept from farm to fork
N2  - Methicillin-resistente Staphylococcus aureus (MRSA) zählen zu den bedeutendsten antibiotikaresistenten Pathogenen, die vor allem in Krankenhäusern aber auch außerhalb von Einrichtungen des Gesundheitswesens weit verbreitet sind. Seit einigen Jahren ist eine neue Generation von MRSA auf dem Vormarsch, die vor allem Nutztierbestände als neue Nische besiedelt. Diese sogenannten Nutztier-assoziierten MRSA wurden wiederholt bei wirtschaftlich bedeutenden Nutztieren sowie daraus gewonnenem Fleisch nachgewiesen. 
Im Rahmen der vorliegenden Arbeit wurde ein methodischer Ansatz verfolgt, um die Hypothese einer möglichen Übertragung von Nutztier-assoziierten MRSA entlang der Lebensmittelkette vom Tier auf dessen Fleisch zu bestätigen. Angepasst an die Unterschiede in den verfügbaren Daten wurden dafür zwei neue Konzepte erstellt. 
Zur Analyse der Übertragung von MRSA entlang der Schlachtkette wurde ein mathematisches Modell des Schweineschlachtprozesses entwickelt, welches dazu geeignet ist, den Verlauf der MRSA-Prävalenz entlang der Schlachtkette zu quantifizieren sowie kritische Prozessschritte für eine MRSA-Übertragung zu identifizieren. Anhand von Prävalenzdaten ist es dem Modell möglich, die durchschnittlichen MRSA-Eliminations- und Kontaminationsraten jedes einzelnen Prozessschrittes zu schätzen, die anschließend in eine Monte-Carlo-Simulation einfließen. Im Ergebnis konnte gezeigt werden, dass es generell möglich ist, die MRSA Prävalenz im Laufe des Schlachtprozesses auf ein niedriges finales Niveau zwischen 0,15 bis 1,15% zu reduzieren. Vor allem das Brühen und Abflämmen der Schlachtkörper wurden als kritische Prozesse im Hinblick auf eine MRSA-Dekontamination identifiziert.
In Deutschland werden regelmäßig MRSA-Prävalenz und Typisierungsdaten auf allen Stufen der Lebensmittelkette verschiedener Nutztiere erfasst. Um die MRSA-Daten dieser Querschnittstudie hinsichtlich einer möglichen Übertragung entlang der Kette zu analysieren, wurde ein neuer statistischer Ansatz entwickelt. Hierfür wurde eine Chi-Quadrat-Statistik mit der Berechnung des Czekanowski-Ähnlichkeitsindex kombiniert, um Unterschiede in der Verteilung stammspezifischer Eigenschaften zwischen MRSA aus dem Stall, von Karkassen nach der Schlachtung und aus Fleisch im Einzelhandel zu quantifizieren. Die Methode wurde am Beispiel der Putenfleischkette implementiert und zudem bei der Analyse der Kalbfleischkette angewendet. Die durchgehend hohen Ähnlichkeitswerte zwischen den einzelnen Proben weisen auf eine mögliche Übertragung von MRSA entlang der Lebensmittelkette hin.
Die erarbeiteten Methoden sind nicht spezifisch bezüglich Prozessketten und Pathogenen. Sie bieten somit einen großen Anwendungsbereich und erweitern das Methodenspektrum zur Bewertung bakterieller Übertragungswege.
N2  - Methicillin resistant Staphylococcus aureus (MRSA) is one of the most important antibiotic-resistant pathogens in hospitals and the community. Recently, a new generation of MRSA, the so called livestock associated (LA) MRSA, has emerged occupying food producing animals as a new niche. LA-MRSA can be regularly isolated from economically important live-stock species including corresponding meats. The present thesis takes a methodological approach to confirm the hypothesis that LA-MRSA are transmitted along the pork, poultry and beef production chain from animals at farm to meat on consumers` table. Therefore two new concepts were developed, adapted to differing data sets.
A mathematical model of the pig slaughter process was developed which simulates the change in MRSA carcass prevalence during slaughter with special emphasis on identifying critical process steps for MRSA transmission. Based on prevalences as sole input variables the model framework is able to estimate the average value range of both the MRSA elimination and contamination rate of each of the slaughter steps. These rates are then used to set up a Monte Carlo simulation of the slaughter process chain. The model concludes that regardless of the initial extent of MRSA contamination low outcome prevalences ranging between 0.15 and 1.15 % can be achieved among carcasses at the end of slaughter. Thus, the model demonstrates that the standard procedure of pig slaughtering in principle includes process steps with the capacity to limit MRSA cross contamination. Scalding and singeing were identified as critical process steps for a significant reduction of superficial MRSA contamination. 
In the course of the German national monitoring program for zoonotic agents MRSA prevalence and typing data are regularly collected covering the key steps of different food production chains. A new statistical approach has been proposed for analyzing this cross sectional set of MRSA data with regard to show potential farm to fork transmission. For this purpose, chi squared statistics was combined with the calculation of the Czekanowski similarity index to compare the distributions of strain specific characteristics between the samples from farm, carcasses after slaughter and meat at retail. The method was implemented on the turkey and veal production chains and the consistently high degrees of similarity which have been revealed between all sample pairs indicate MRSA transmission along the chain.
As the proposed methods are not specific to process chains or pathogens they offer a broad field of application and extend the spectrum of methods for bacterial transmission assessment.
KW  - MRSA
KW  - Antibiotikaresistenz
KW  - Modell
KW  - Lebensmittelkette
KW  - Übertragung
KW  - MRSA
KW  - Resistance
KW  - Model
KW  - Food Chain
KW  - Transmission
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-85918
ER  - 
TY  - JOUR
A1  - Lohren, Hanna
A1  - Blagojevic, Lara
A1  - Fitkau, Romy
A1  - Ebert, Franziska
A1  - Schildknecht, Stefan
A1  - Leist, Marcel
A1  - Schwerdtle, Tanja
T1  - Toxicity of organic and inorganic mercury species in human neurons and human astrocytes
JF  - Journal of trace elements in medicine and biology
N2  - Organic mercury (Hg) species exert their toxicity primarily in the central nervous system. The food relevant Hg species methylmercury (MeHg) has been frequently studied regarding its neurotoxic effects in vitro and in vivo. Neurotoxicity of thiomersal, which is used as a preservative in medical preparations, is to date less characterised. Due to dealkylation of organic Hg or oxidation of elemental Hg, inorganic Hg is present in the brain albeit these species are not able to readily cross the blood brain barrier. This study compared for the first time toxic effects of organic MeHg chloride (MeHgCl) and thiomersal as well as inorganic mercury chloride (HgCl2) in differentiated human neurons (LUHMES) and human astrocytes (CCF-STTG1). The three Hg species differ in their degree and mechanism of toxicity in those two types of brain cells. Generally, neurons are more susceptible to Hg species induced cytotoxicity as compared to astrocytes. This might be due to the massive cellular mercury uptake in the differentiated neurons. The organic compounds exerted stronger cytotoxic effects as compared to inorganic HgCl2. In contrast to HgCl2 exposure, organic Hg compounds seem to induce the apoptotic cascade in neurons following low-level exposure. No indicators for apoptosis were identified for both inorganic and organic mercury species in astrocytes. Our studies clearly demonstrate species-specific toxic mechanisms. A mixed exposure towards all Hg species in the brain can be assumed. Thus, prospectively coexposure studies as well as cocultures of neurons and astrocytes could provide additional information in the investigation of Hg induced neurotoxicity.
KW  - Methylmercury
KW  - Thiomersal
KW  - Mercuric mercury
KW  - Human differentiated neurons
KW  - Cytotoxicity
KW  - Apoptosis
Y1  - 2015
U6  - https://doi.org/10.1016/j.jtemb.2015.06.008
SN  - 0946-672X
VL  - 32
SP  - 200
EP  - 208
PB  - Elsevier
CY  - Jena
ER  - 
TY  - THES
A1  - Meyer, Sören
T1  - Toxicity and toxicokinetics of arsenolipids and their metabolites
Y1  - 2015
ER  - 
TY  - JOUR
A1  - Prüfer, Nicole
A1  - Kleuser, Burkhard
A1  - van der Giet, Markus
T1  - The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
JF  - Biological chemistry
N2  - The high-density lipoprotein (HDL) is one of the most important endogenous cardiovascular protective markers. HDL is an attractive target in the search for new pharmaceutical therapies and in the prevention of cardiovascular events. Some of HDL's anti-atherogenic properties are related to the signaling molecule sphingosine-1-phosphate (S1P), which plays an important role in vascular homeostasis. However, for different patient populations it seems more complicated. Significant changes in HDL's protective potency are reduced under pathologic conditions and HDL might even serve as a proatherogenic particle. Under uremic conditions especially there is a change in the compounds associated with HDL. S1P is reduced and acute phase proteins such as serum amyloid A (SAA) are found to be elevated in HDL. The conversion of HDL in inflammation changes the functional properties of HDL. High amounts of SAA are associated with the occurrence of cardiovascular diseases such as atherosclerosis. SAA has potent pro-atherogenic properties, which may have impact on HDL's biological functions, including cholesterol efflux capacity, antioxidative and anti-inflammatory activities. This review focuses on two molecules that affect the functionality of HDL. The balance between functional and dysfunctional HDL is disturbed after the loss of the protective sphingolipid molecule S1P and the accumulation of the acute-phase protein SAA. This review also summarizes the biological activities of lipid-free and lipid-bound SAA and its impact on HDL function.
KW  - atherosclerosis
KW  - high-density lipoprotein (HDL)
KW  - inflammation
KW  - serum amyloid A (SAA)
KW  - sphingosine-1-phosphate (S1P)
Y1  - 2015
U6  - https://doi.org/10.1515/hsz-2014-0192
SN  - 1431-6730
SN  - 1437-4315
VL  - 396
IS  - 6-7
SP  - 573
EP  - 583
PB  - De Gruyter
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Kana-Sop, Marie Modestine
A1  - Gouado, Inocent
A1  - Achu, Mercy Bih
A1  - Van Camp, John
A1  - Zollo, Paul Henri Amvam
A1  - Schweigert, Florian J.
A1  - Oberleas, Donald
A1  - Ekoe, Tetanye
T1  - The Influence of Iron and Zinc Supplementation on the Bioavailability of Provitamin A Carotenoids from Papaya Following Consumption of a Vitamin A-Deficient Diet
JF  - Journal of nutritional science and vitaminology
N2  - Iron deficiency anemia, zinc and vitamin A deficiencies are serious public health problems in Cameroon, as in many developing countries. Local vegetables which are sources of provitamin A carotenoids (PACs) can be used to improve vitamin A intakes. However, traditional meals are often unable to cover zinc and iron needs. The aim of this study was to determine the bioavailability of 3 PACs (alpha-carotene, beta-carotene, and beta-cryptoxanthin) in young men, who were fed with a vitamin A-free diet and received iron and zinc supplementation. Twelve healthy participants were divided into three groups and were supplemented with elemental iron (20 mg of iron fumarate), 20 mg of zinc sulfate or iron + zinc (20 mg of iron in the morning and 20 mg of zinc in the evening) for 11 d. They were given a vitamin A- and PAC-free diet from the 6th to the 11th day, followed by a test meal containing 0.55 kg of freshly peeled papaya as a source of PACs. Blood samples were collected four times successively on the 11th day (the test meal day), at TO (just after the test meal), after 2 h (T2), after 4 h (T4) and after 7 h (T7). Ultracentrifugation was used to isolate serum chylomicrons. Retinol appearance and PAC postprandial concentrations were determined. The supplementation with zinc, iron and iron+zinc influenced the chylomicron appearance of retinol and PACs differently as reflected by retention times and maximum absorption peaks. Iron led to highest retinol levels in the chylomicron. Zinc and iron+zinc supplements were best for optimal intact appearance of alpha-carotene, beta-carotene and beta-cryptoxanthin respectively. Supplementation with iron led to the greatest bioavailability of PACs from papaya and its conversion to retinol.
KW  - micronutrient deficiencies
KW  - zinc/iron supplementation
KW  - carotenoids bioavailability
KW  - Cameroon
Y1  - 2015
SN  - 0301-4800
SN  - 1881-7742
VL  - 61
IS  - 3
SP  - 205
EP  - 214
PB  - Univ. of Tokyo Pr.
CY  - Tokyo
ER  -