TY - JOUR A1 - Yang, Fang A1 - Lai, Xinlong A1 - Deng, Li A1 - Liu, Xiaoxiao A1 - Li, Jian A1 - Zeng, Shuixiu A1 - Zhang, Cheng A1 - Hocher, Carl-Friedrich A1 - Hocher, Berthold T1 - Association of endothelin-1 gene polymorphisms with the clinical phenotype in primary nephrotic syndrome of children JF - Life sciences : molecular, cellular and functional basis of therapy N2 - Aims:This study aims to investigate the relationship between plasma endothelin-1 (ET-1) concentrations, ET-1 gene polymorphisms in loci rs5370, rs1630736, 3A/4A and clinical features of primary nephrotic syndrome (NS) in children. Materials and methods: Thirty-six children with primary NS were selected as case group, and 94 healthy children were selected as control group. All subjects were genotyped for three single nucleotide polymorphisms (SNPs) (rs5370, rs10478694 [3A4A) and rs 1630736) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using a radio-immunoassay. Key findings: Plasma ET-1 concentrations were higher in NS patients (P = 0.007) as compared to healthy children. The allele frequencies between control and NS patients were significantly different only with respect to the rs10478694 SNP of the ET-1 gene. The allele frequencies between control and NS patients for the rs5370 SNP showed a trend towards difference (P = 0.057). Plasma cholesterol in NS patients is associated with both: the Cl genotype in locus rs5370 and the 3A4A genotype in locus rs10478694 (P < 0.05 in both cases). Significance: The ET systems might play a disease modifying role in pediatric NS. Plasma cholesterol, a hallmark of NS. seems to be associated with genetic variations within the human ET-1 gene. (C) 2014 Elsevier Inc. All rights reserved. KW - Endothelin-1 KW - Gene polymorphism KW - Childhood nephrotic syndrome KW - Cholesterol Y1 - 2014 U6 - https://doi.org/10.1016/j.lfs.2014.04.010 SN - 0024-3205 SN - 1879-0631 VL - 118 IS - 2 SP - 446 EP - 450 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Yamamoto, Masayoshi A1 - Baldermann, Susanne A1 - Yoshikawa, Keisuke A1 - Fujita, Akira A1 - Mase, Nobuyuki A1 - Watanabe, Naoharu T1 - Determination of volatile compounds in four commercial samples of japanese green algae using solid phase microextraction gas chromatography mass spectrometry JF - The ScientificWorld journal N2 - Green algae are of great economic importance. Seaweed is consumed fresh or as seasoning in Japan. The commercial value is determined by quality, color, and flavor and is also strongly influenced by the production area. Our research, based on solid phase microextraction gas chromatography mass spectrometry (SPME-GC-MS), has revealed that volatile compounds differ intensely in the four varieties of commercial green algae. Accordingly, 41 major volatile compounds were identified. Heptadecene was the most abundant compound from Okayama (Ulva prolifera), Tokushima (Ulva prolifera), and Ehime prefecture (Ulva linza). Apocarotenoids, such as ionones, and their derivatives were prominent volatiles in algae from Okayama (Ulva prolifera) and Tokushima prefecture (Ulva prolifera). Volatile, short chained apocarotenoids are among the most potent flavor components and contribute to the flavor of fresh, processed algae, and algae-based products. Benzaldehyde was predominant in seaweed from Shizuoka prefecture (Monostroma nitidum). Multivariant statistical analysis (PCA) enabled simple discrimination of the samples based on their volatile profiles. This work shows the potential of SPME-GC-MS coupled with multivariant analysis to discriminate between samples of different geographical and botanical origins and form the basis for development of authentication methods of green algae products, including seasonings. Y1 - 2014 U6 - https://doi.org/10.1155/2014/289780 SN - 1537-744X PB - Hindawi Publishing Corp. CY - New York ER - TY - JOUR A1 - Vignon-Zellweger, Nicolas A1 - Relle, Katharina A1 - Rahnenfuehrer, Jan A1 - Schwab, Karima A1 - Hocher, Berthold A1 - Theuring, Franz T1 - Endothelin-1 overexpression and endothelial nitric oxide synthase knock-out induce different pathological responses in the heart of male and female mice JF - Life sciences : molecular, cellular and functional basis of therapy N2 - Aims: The nitric oxide and endothelin systems are key components of a local paracrine hormone network in the heart. We previously reported that diastolic dysfunction observed in mice lacking the endothelial nitric oxide synthase (eNOS-/-) can be prevented by a genetic overexpression of ET-1. Sexual dimorphisms have been reported in both ET-1 and NO systems. Particularly, eNOS-/- mice present sex related phenotypic differences. Main methods: We used the ET-1 transgenic (ET+/+), eNOS-/-, and crossbred ET+/+ eNOS-/- mice, and wild type controls. We measured cardiac function by heart catheterization. Cardiac ventricles were collected for histological and molecular profiling. Key findings: We report here that (i) the level of ET-1 expression in eNOS-/- mice was elevated in males but not in females. (ii) Left ventricular end-diastolic blood pressure was higher in male eNOS-/- mice than in females. (ii) eNOS-/- males but not females developed cardiomyocyte hypertrophy. (iv) Perivascular fibrosis of intra-cardiac arteries developed in female ET+/+ and eNOS-/- mice but not in males. Additionally, (v) the cardiac expression of metalloprotease-9 was higher in eNOS-/- males compared to females. Finally, (vi) cardiac proteome analysis revealed that the protein abundance of the oxidative stress related enzyme superoxide dismutase presented with sexual dimorphism in eNOS-/- and ET+/+ mice. Significance: These results indicate that the cardiac phenotypes of ET-1 transgenic mice and eNOS knockout mice are sex specific. Since both systems are key players in the pathogenesis of cardiovascular diseases, our findings might be important in the context of gender differences in patients with such diseases. (C) 2013 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). KW - Endothelin-1 KW - Nitric oxide KW - Cardiac function KW - Sexual dimorphism Y1 - 2014 U6 - https://doi.org/10.1016/j.lfs.2013.12.003 SN - 0024-3205 SN - 1879-0631 VL - 118 IS - 2 SP - 219 EP - 225 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Unterberg, Marlies A1 - Leffers, Larissa A1 - Huebner, Florian A1 - Humpf, Hans-Ulrich A1 - Lepikhov, Konstantin A1 - Walter, Joern A1 - Ebert, Franziska A1 - Schwerdtle, Tanja T1 - Toxicity of arsenite and thio-DMA(V) after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics JF - Toxicology research N2 - This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAs(III) and its metabolite thio-DMA(V) were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAs(III) and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMA(V). Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAs(III) and thio-DMA(V) caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMA(V); iAs(III) induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies. Y1 - 2014 U6 - https://doi.org/10.1039/c4tx00036f SN - 2045-452X SN - 2045-4538 VL - 3 IS - 6 SP - 456 EP - 464 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Uhr, Linda A1 - Buchholz, Tina A1 - Homann, Thomas A1 - Huschek, Gerd A1 - Rawel, Harshadrai Manilal T1 - Targeted proteomics-based analysis of technical enzymes from fungal origin in baked products JF - Journal of cereal science N2 - The application of technical enzymes is a potential tool in modulating the dough and baking quality of cereal products. No endogenous amylases (alpha- and beta-forms) are present in mature wheat grains; they may be synthesized or activated during germination. Hence, microbial alpha-amylases are added to the dough, being resistant to the endogenous alpha-amylase/trypsin inhibitors. Here, we report on the initial identification of two technical enzymes from a commercial sample based on an in-gel tryptic digestion coupled with MALDI-MS analysis. The primary component of the protein fraction with 51.3 kDa was alpha-amylase from Aspergillus species. A second major protein with 24.8 kDa was identified as endo-1,4-xylanase from Thermomyces lanuginosus. In the following experimental work up, a targeted proteomics approach utilizing the combination of specific proteolytic digestion of the added amylase and xylanase in wheat flour, dough or baked products, solid phase extraction of released peptides and their detection using LC-MS/MS was optimized. The targeted (MRM) MS/MS peptide signals showed that the peptide "ALSSALHER" (MW = 983) originating from amylase and "GWNPGLNAR" (MW = 983) from xylanase can be used to identify the corresponding technical enzymes added. Consequently, locally available baked products were tested and found to contain these enzymes as supplementary ingredients. (C) 2014 Elsevier Ltd. All rights reserved. KW - Technical enzymes KW - Amylase KW - Xylanase KW - Mass spectrometry Y1 - 2014 U6 - https://doi.org/10.1016/j.jcs.2014.04.007 SN - 0733-5210 SN - 1095-9963 VL - 60 IS - 2 SP - 440 EP - 447 PB - Elsevier CY - London ER - TY - JOUR A1 - Tu, Vo Anh A1 - Kaga, Atsushi A1 - Gericke, Karl-Heinz A1 - Watanabe, Naoharu A1 - Narumi, Tetsuo A1 - Toda, Mitsuo A1 - Brueckner, Bernhard A1 - Baldermann, Susanne A1 - Mase, Nobuyuki T1 - Synthesis and characterization of quantum dot nanoparticles bound to the plant volatile precursor of Hydroxy-apo-10'-carotenal JF - The journal of organic chemistry N2 - This study is focused on the synthesis and characterization of hydroxy-apo-10'-carotenal/quantum dot (QD) conjugates aiming at the in vivo visualization of beta-ionone, a carotenoid-derived volatile compound known for its important contribution to the flavor and aroma of many fruits, vegetables, and plants. The synthesis of nanoparticles bound to plant volatile precursors was achieved via coupling reaction of the QD to C-27-aldehyde which was prepared from alpha-ionone via 12 steps in 2.4% overall yield. The formation of the QD-conjugate was confirmed by measuring its fluorescence spectrum to observe the occurrence of fluorescence resonance energy transfer. Y1 - 2014 U6 - https://doi.org/10.1021/jo500605c SN - 0022-3263 VL - 79 IS - 15 SP - 6808 EP - 6815 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Taleshi, Mojtaba S. A1 - Seidler-Egdal, Rune K. A1 - Jensen, Kenneth Bendix A1 - Schwerdtle, Tanja A1 - Francesconi, Kevin A. T1 - Synthesis and Characterization of Arsenolipids: Naturally Occurring Arsenic Compounds in Fish and Algae JF - Organometallics N2 - Arsenic-containing lipids (arsenolipids) are natural products present in fish and algae. Because these compounds occur in foods, there is considerable interest in their human toxicology. We report the synthesis and characterization of seven arsenic-containing lipids, including six natural products. The compounds comprise dimethylarsinyl groups attached to saturated long-chain hydrocarbons (three compounds), saturated long-chain fatty acids (two compounds), and monounsaturated long chain fatty acids (two compounds). The arsenic group was introduced through sodium dimethylarsenide or bis(dimethylarsenic) oxide. The latter route provided higher and more reproducible yields, and consequently, this pathway was followed to synthesize six of the seven compounds. Mass spectral properties are described to assist in the identification of these compounds in natural samples. The pure synthesized arsenolipids will be used for in vitro experiments with human cells to test their uptake, biotransformation, and possible toxic effects. Y1 - 2014 U6 - https://doi.org/10.1021/om4011092 SN - 0276-7333 SN - 1520-6041 VL - 33 IS - 6 SP - 1397 EP - 1403 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Sic, Heiko A1 - Kraus, Helene A1 - Madl, Josef A1 - Flittner, Karl-Andreas A1 - von Muenchow, Audrey Lilly A1 - Pieper, Kathrin A1 - Rizzi, Marta A1 - Kienzler, Anne-Kathrin A1 - Ayata, Korcan A1 - Rauer, Sebastian A1 - Kleuser, Burkhard A1 - Salzer, Ulrich A1 - Burger, Meike A1 - Zirlik, Katja A1 - Lougaris, Vassilios A1 - Plebani, Alessandro A1 - Roemer, Winfried A1 - Loeffler, Christoph A1 - Scaramuzza, Samantha A1 - Villa, Anna A1 - Noguchi, Emiko A1 - Grimbacher, Bodo A1 - Eibel, Hermann T1 - Sphingosine-1-phosphate receptors control B-cell migration through signaling components associated with primary immunodeficiencies, chronic lymphocytic leukemia, and multiple sclerosis JF - The journal of allergy and clinical immunology N2 - Background: Five different G protein-coupled sphingosine-1-phosphate (S1P) receptors (S1P1-S1P5) regulate a variety of physiologic and pathophysiologic processes, including lymphocyte circulation, multiple sclerosis (MS), and cancer. Although B-lymphocyte circulation plays an important role in these processes and is essential for normal immune responses, little is known about S1P receptors in human B cells. Objective: To explore their function and signaling, we studied B-cell lines and primary B cells from control subjects, patients with leukemia, patients with S1P receptor inhibitor-treated MS, and patients with primary immunodeficiencies. Methods: S1P receptor expression was analyzed by using multicolor immunofluorescence microscopy and quantitative PCR. Transwell assays were used to study cell migration. S1P receptor internalization was visualized by means of time-lapse imaging with fluorescent S1P receptor fusion proteins expressed by using lentiviral gene transfer. B-lymphocyte subsets were characterized by means of flow cytometry and immunofluorescence microscopy. Results: Showing that different B-cell populations express different combinations of S1P receptors, we found that S1P1 promotes migration, whereas S1P4 modulates and S1P2 inhibits S1P1 signals. Expression of CD69 in activated B lymphocytes and B cells from patients with chronic lymphocytic leukemia inhibited S1P-induced migration. Studying B-cell lines, normal B lymphocytes, and B cells from patients with primary immunodeficiencies, we identified Bruton tyrosine kinase, beta-arrestin 2, LPS-responsive beige-like anchor protein, dedicator of cytokinesis 8, and Wiskott-Aldrich syndrome protein as critical signaling components downstream of S1P1. Conclusion: Thus S1P receptor signaling regulates human B-cell circulation and might be a factor contributing to the pathology of MS, chronic lymphocytic leukemia, and primary immunodeficiencies. KW - Sphingosine-1-phosphate KW - B cells KW - migration KW - autoimmunity KW - circulation KW - fingolimod KW - FTY720 KW - primary immunodeficiencies Y1 - 2014 U6 - https://doi.org/10.1016/j.jaci.2014.01.037 SN - 0091-6749 SN - 1097-6825 VL - 134 IS - 2 SP - 420 EP - + PB - Elsevier CY - New York ER - TY - JOUR A1 - Sharkovska, Yuliya A1 - Reichetzeder, Christoph A1 - Alter, Markus L. A1 - Tsuprykov, Oleg A1 - Bachmann, Sebastian A1 - Secher, Thomas A1 - Klein, Thomas A1 - Hocher, Berthold T1 - Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy JF - Journal of hypertension N2 - Background: Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear. Method: This study examined the long-term renoprotective effects of DPP-4 inhibitor linagliptin in db/db mice, a model of type 2 diabetes. Results were compared with the known beneficial effects of renin-angiotensin system blockade by enalapril. Ten-week-old male diabetic db/db mice were treated for 3 months with either vehicle (n = 10), 3 mg linagliptin/kg per day (n = 8), or 20 mg enalapril/kg per day (n = 10). Heterozygous db/m mice treated with vehicle served as healthy controls (n = 8). Results: Neither linagliptin nor enalapril had significant effects on the parameters of glucose metabolism or blood pressure in diabetic db/db mice. However, linagliptin treatment reduced albuminuria and attenuated kidney injury. In addition, expression of podocyte marker podocalyxin was normalized. We also analysed DPP-4 expression by immunofluorescence in human kidney biopsies and detected upregulation of DPP-4 in the glomeruli of patients with diabetic nephropathy, suggesting that our findings might be of relevance for human kidney disease as well. Conclusion: Treatment with DPP-4 inhibitor linagliptin delays the progression of diabetic nephropathy damage in a glucose-independent and blood-pressure-independent manner. The observed effects may be because of the attenuation of podocyte injury and inhibition of myofibroblast transformation. KW - diabetic nephropathy KW - DPP-4 inhibitors KW - linagliptin Y1 - 2014 U6 - https://doi.org/10.1097/HJH.0000000000000328 SN - 0263-6352 SN - 1473-5598 VL - 32 IS - 11 SP - 2211 EP - 2223 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - CHAP A1 - Scholze, Alexandra A1 - Petersen, Lise A1 - Hocher, Berthold A1 - Rasmussen, Lars M. A1 - Tepel, Martin T1 - Role of fibroblast growth factor-23 and soluble alpha klotho in chronic kidney disease T2 - Nephrology, dialysis, transplantation Y1 - 2014 SN - 0931-0509 SN - 1460-2385 VL - 29 SP - 120 EP - 121 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Scholze, Alexandra A1 - Liu, Ying A1 - Pedersen, Lise A1 - Xia, Shengqiang A1 - Roth, Heinz J. A1 - Hocher, Berthold A1 - Rasmussen, Lars Melholt A1 - Tepel, Martin T1 - Soluble alpha-Klotho and its relation to kidney function and fibroblast growth factor-23 JF - The journal of clinical endocrinology & metabolism N2 - Context: Relations between fibroblast growth factor-23 (FGF-23), soluble alpha-klotho (s-alpha-klotho), and kidney function in chronic kidney disease (CKD) are still unclear. Especially the role of s-alpha-klotho requires further study. Objectives: Our objectives were to analyze the relation of s-alpha-klotho to estimated glomerular filtration rate (eGFR), FGF-23, and other parameters of calcium-phosphate metabolism and to investigate the response of s-alpha-klotho to cholecalciferol. Patients, Design, and Setting: Twenty-four CKD (stage 1-5) patients participated in this 8-week randomized controlled trial (vitamin D and chronic renal insufficiency). Interventions: Interventions included 40 000 IU cholecalciferol or placebo weekly. Main Outcome Measure: S-alpha-klotho was determined by ELISA with antihuman klotho antibodies 67G3 and 91F1. Results: For all patients, s-alpha-klotho concentrations did not differ between CKD stages. When patients were subdivided based on FGF-23 concentrations, a positive association of s-alpha-klotho with eGFR became apparent in patients with lower than median FGF-23 concentrations but not in those above median value. Patients with s-alpha-klotho below 204 pg/mL showed higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase compared with patients with higher s-alpha-klotho. Treatment with cholecalciferol significantly increased 1,25-dihydroxyvitamin D. The increase of FGF-23 had only borderline significance. There was no significant effect of high-dose cholecalciferol administration for 8 weeks on plasma s-alpha-klotho. Conclusions: CKD patients with s-alpha-klotho below 204 pg/mL had higher age, lower phosphate clearance, and lower bone-specific alkaline phosphatase. An association of s-alpha-klotho with eGFR was observed only in the presence of close to normal, but not high, FGF-23 concentrations. Cholecalciferol treatment did not change s-alpha-klotho concentrations. Y1 - 2014 U6 - https://doi.org/10.1210/jc.2013-4171 SN - 0021-972X SN - 1945-7197 VL - 99 IS - 5 SP - E855 EP - E861 PB - Endocrine Society CY - Washington ER - TY - THES A1 - Schmiedchen, Bettina T1 - Vitamin D and its linkage between chronic kidney disease and cardiovascular integrity Y1 - 2014 ER - TY - JOUR A1 - Reichetzeder, Christoph A1 - Tsuprykov, Oleg A1 - Hocher, Berthold T1 - Endothelin receptor antagonists in clinical research - Lessons learned from preclinical and clinical kidney studies JF - Life sciences : molecular, cellular and functional basis of therapy N2 - Endothelin receptor antagonists (ETRAs) are approved for the treatment of pulmonary hypertension and scleroderma-related digital ulcers. The efforts to approve this class of drugs for renal indications, however, failed so far. Preclinical studies were promising. Transgenic overexpression of ET-1 or ET-2 in rodents causes chronic renal failure. Blocking the ET system was effective in the treatment of renal failure in rodent models. However, various animal studies indicate that blocking the renal tubular ETAR and ETBR causes water and salt retention partially mediated via the epithelial sodium transporter in tubular cells. ETRAs were successfully tested clinically in renal indications in phase 2 trials for the treatment of diabetic nephropathy. They showed efficacy in terms of reducing albumin excretion on top of guideline based background therapy (RAS blockade). However, these promising results could not be translated to successful phase Ill trials so far. The spectrum of serious adverse events was similar to other phase III trials using ETRAs. Potential underlying reasons for these failures and options to solve these issues are discussed. In addition preclinical and clinical studies suggest caution when addressing renal patient populations such as patients with hepatorenal syndrome, patients with any type of cystic kidney disease and patients at risk of contrast media induced nephropathy. The lessons learned in renal indications are also important for other potential promising indications of ETRAs like cancer and heart failure. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). KW - Endothelin receptor antagonists KW - Kidney KW - Side effects KW - Safety KW - Water and salt retention KW - Clinical trials Y1 - 2014 U6 - https://doi.org/10.1016/j.lfs.2014.02.025 SN - 0024-3205 SN - 1879-0631 VL - 118 IS - 2 SP - 141 EP - 148 PB - Elsevier CY - Oxford ER - TY - CHAP A1 - Reichetzeder, Christoph A1 - Pasch, A. A1 - von Websky, Karoline A1 - Tsuprykov, Oleg A1 - Klein, T. A1 - Hocher, Berthold T1 - The DPP-4 inhibitor linagliptin increases plasma fetuin-A concentrations in a rat model of uraemic calcification T2 - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) Y1 - 2014 SN - 0012-186X SN - 1432-0428 VL - 57 SP - S522 EP - S522 PB - Springer CY - New York ER - TY - JOUR A1 - Reichetzeder, Christoph A1 - Chen, Hong A1 - Foeller, Michael A1 - Slowinski, Torsten A1 - Li, Jian A1 - Chen, You-Peng A1 - Lang, Florian A1 - Hocher, Berthold T1 - Maternal vitamin D deficiency and fetal programming - lessons learned from humans and mice JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Background/Aims: Cardiovascular disease partially originates from poor environmental and nutritional conditions in early life. Lack of micronutrients like 25 hydroxy vitamin D-3 (25OHD) during pregnancy may be an important treatable causal factor. The present study explored the effect of maternal 25OHD deficiency on the offspring. Methods: We performed a prospective observational study analyzing the association of maternal 25OHD deficiency during pregnancy with birth outcomes considering confounding. To show that vitamin D deficiency may be causally involved in the observed associations, mice were set on either 25OHD sufficient or insufficient diets before and during pregnancy. Growth, glucose tolerance and mortality was analyzed in the F1 generation. Results: The clinical study showed that severe 25OHD deficiency was associated with low birth weight and low gestational age. ANCOVA models indicated that established confounding factors such as offspring sex, smoking during pregnancy and maternal BMI did not influence the impact of 25OHD on birth weight. However, there was a significant interaction between 25OHD and gestational age. Maternal 25OHD deficiency was also independently associated with low APGAR scores 5 minutes postpartum. The offspring of 25OHD deficient mice grew slower after birth, had an impaired glucose tolerance shortly after birth and an increased mortality during follow-up. Conclusions: Our study demonstrates an association between maternal 25OHD and offspring birth weight. The effect of 25OHD on birth weight seems to be mediated by vitamin D controlling gestational age. Results from an animal experiment suggest that gestational 25OHD insufficiency is causally linked to adverse pregnancy outcomes. Since birth weight and prematurity are associated with an adverse cardiovascular outcome in later life, this study emphasizes the need for novel monitoring and treatment guidelines of vitamin D deficiency during pregnancy. KW - Vitamin D KW - Birth weight KW - Preterm delivery KW - Fetal programming KW - Glucose tolerance KW - Cardiovascular diseases Y1 - 2014 U6 - https://doi.org/10.1159/000355809 SN - 1420-4096 SN - 1423-0143 VL - 39 IS - 4 SP - 315 EP - 329 PB - Karger CY - Basel ER - TY - JOUR A1 - Raila, Jens A1 - Schweigert, Florian J. A1 - Kohn, Barbara T1 - Relationship between urinary Tamm-Horsfall protein excretion and renal function in dogs with naturally occurring renal disease JF - Veterinary clinical pathology N2 - Background Tamm-Horsfall protein (THP) is physiologically excreted in urine, but little is known about the role of THP in the diagnosis of renal disease in dogs. Objective The aim of this study was to evaluate to which extent naturally occurring renal disease affects the urinary excretion of THP. Methods Dogs were divided into 5 groups according to plasma creatinine concentration, urinary protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P-ClCr) rates: Group A (healthy control dogs; n=8), nonazotemic and nonproteinuric dogs, with P-ClCr rates > 90mL/min/m2; group B (n=25), nonazotemic and nonproteinuric dogs with reduced P-ClCr rates (51-89mL/min/m2); group C (n=7), nonazotemic but proteinuric dogs with P-ClCr rates 53-98mL/min/m2; group D (n=8), azotemic and borderline proteinuric dogs (P-ClCr rates: 22-45mL/min/m2); and group E (n=15), azotemic and proteinuric dogs (not tested for P-ClCr). THP was measured by quantitative Western blot analysis, and the ratio of THP-to-urinary creatinine (THP/UC) was calculated. Results The THP/UC concentrations were not different among dogs of groups A-D, but were reduced in dogs of group E (P<.001). THP/UC correlated negatively with serum creatinine (P<.01) and UP/UC (P<.01), but was not significantly associated with P-ClCr. Conclusions Decreased levels of THP/UC were present in moderately to severely azotemic and proteinuric dogs. This suggests tubular injury in these dogs and that THP might be useful as urinary marker to study the pathogenesis of renal disease. KW - Distal tubules KW - dog KW - kidney KW - lower nephron KW - proteinuria KW - urine Y1 - 2014 U6 - https://doi.org/10.1111/vcp.12143 SN - 0275-6382 SN - 1939-165X VL - 43 IS - 2 SP - 261 EP - 265 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Putra, Sulistyo Emantoko Dwi A1 - Tsuprykov, Oleg A1 - Von Websky, Karoline A1 - Ritter, Teresa A1 - Reichetzeder, Christoph A1 - Hocher, Berthold T1 - Dealing with large sample sizes: comparison of a new one spot dot blot method to western blot JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Western blot is the gold standard method to determine individual protein expression levels. However, western blot is technically difficult to perform in large sample sizes because it is a time consuming and labor intensive process. Dot blot is often used instead when dealing with large sample sizes, but the main disadvantage of the existing dot blot techniques, is the absence of signal normalization to a housekeeping protein. Methods: In this study we established a one dot two development signals (ODTDS) dot blot method employing two different signal development systems. The first signal from the protein of interest was detected by horseradish peroxidase (HRP). The second signal, detecting the housekeeping protein, was obtained by using alkaline phosphatase (AP). Results: Inter-assay results variations within ODTDS dot blot and western blot and intra-assay variations between both methods were low (1.04 - 5.71%) as assessed by coefficient of variation. Conclusions: ODTDS dot blot technique can be used instead of western blot when dealing with large sample sizes without a reduction in results accuracy. KW - one dot two development signals (ODTDS) dot blot KW - western blot KW - protein quantification KW - large sample size studies KW - comparison Y1 - 2014 U6 - https://doi.org/10.7754/Clin.Lab.2014.140317 SN - 1433-6510 VL - 60 IS - 11 SP - 1871 EP - 1877 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Putra, Sulistyo Emantoko Dwi A1 - Neuber, Corinna A1 - Reichetzeder, Christoph A1 - Hocher, Berthold A1 - Kleuser, Burkhard T1 - Analysis of genomic DNA methylation levels in human placenta using liquid Chromatography-Electrospray ionization tandem mass spectrometry JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Background: DNA-methylation is a common epigenetic tool which plays a crucial role in gene regulation and is essential for cell differentiation and embryonic development. The placenta is an important organ where gene activity can be regulated by epigenetic DNA modifications, including DNA methylation. This is of interest as, the placenta is the interface between the fetus and its environment, the mother. Exposure to environmental toxins and nutrition during pregnancy may alter DNA methylation of the placenta and subsequently placental function and as a result the phenotype of the offspring. The aim of this study was to develop a reliable method to quantify DNA methylation in large clinical studies. This will be a tool to analyze the degree of DNA methylation in the human placenta in relationship to clinical readouts. Methods: Liquid chromatography-electrospray ionization/multi-stage mass spectrometry (LC-ESI/MS/MS) technique was used for the quantification of the 5dmC/dG ratio in placentas from 248 healthy pregnancies. We were able to demonstrate that this method is a reliable and stable way to determine global placental DNA methylation in large clinical trials. Results/Conclusion: The degree of placental DNA methylation seen in our pilot study varies substantially from 2% to 5%. The clinical implications of this variation need to be demonstrated in adequately powered large studies. KW - Pregnancy KW - Placenta KW - Methylation KW - Global KW - LC-MS/MS KW - Fetal programming KW - Clinical Y1 - 2014 U6 - https://doi.org/10.1159/000358666 SN - 1015-8987 SN - 1421-9778 VL - 33 IS - 4 SP - 945 EP - 952 PB - Karger CY - Basel ER - TY - JOUR A1 - Pruefer, Jasmin A1 - Schuchardt, Mirjam A1 - Toelle, Markus A1 - Pruefer, Nicole A1 - Hoehne, Matthias A1 - Zidek, Walter A1 - van der Giet, Markus T1 - Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: Induction of mineralization JF - PLoS one N2 - Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteochondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis. Y1 - 2014 U6 - https://doi.org/10.1371/journal.pone.0101709 SN - 1932-6203 VL - 9 IS - 7 PB - PLoS CY - San Fransisco ER - TY - JOUR A1 - Pieper, Imke A1 - Wehe, Christoph A. A1 - Bornhorst, Julia A1 - Ebert, Franziska A1 - Leffers, Larissa A1 - Holtkamp, Michael A1 - Hoeseler, Pia A1 - Weber, Till A1 - Mangerich, Aswin A1 - Buerkle, Alexander A1 - Karst, Uwe A1 - Schwerdtle, Tanja T1 - Mechanisms of Hg species induced toxicity in cultured human astrocytes: genotoxicity and DNA-damage response JF - Metallomics : integrated biometal science N2 - The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co- genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl) ation contributes to organic Hg induced neurotoxicity. Y1 - 2014 U6 - https://doi.org/10.1039/c3mt00337j SN - 1756-5901 SN - 1756-591X VL - 6 IS - 3 SP - 662 EP - 671 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Pewzner-Jung, Yael A1 - Tabazavareh, Shaghayegh Tavakoli A1 - Grassme, Heike A1 - Becker, Katrin Anne A1 - Japtok, Lukasz A1 - Steinmann, Joerg A1 - Joseph, Tammar A1 - Lang, Stephan A1 - Tuemmler, Burkhard A1 - Schuchman, Edward H. A1 - Lentsch, Alex B. A1 - Kleuser, Burkhard A1 - Edwards, Michael J. A1 - Futerman, Anthony H. A1 - Gulbins, Erich T1 - Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa JF - EMBO molecular medicine N2 - Cystic fibrosis patients and patients with chronic obstructive pulmonary disease, trauma, burn wound, or patients requiring ventilation are susceptible to severe pulmonary infection by Pseudomonas aeruginosa. Physiological innate defense mechanisms against this pathogen, and their alterations in lung diseases, are for the most part unknown. We now demonstrate a role for the sphingoid long chain base, sphingosine, in determining susceptibility to lung infection by P.aeruginosa. Tracheal and bronchial sphingosine levels were significantly reduced in tissues from cystic fibrosis patients and from cystic fibrosis mouse models due to reduced activity of acid ceramidase, which generates sphingosine from ceramide. Inhalation of mice with sphingosine, with a sphingosine analog, FTY720, or with acid ceramidase rescued susceptible mice from infection. Our data suggest that luminal sphingosine in tracheal and bronchial epithelial cells prevents pulmonary P.aeruginosa infection in normal individuals, paving the way for novel therapeutic paradigms based on inhalation of acid ceramidase or of sphingoid long chain bases in lung infection. KW - cystic fibrosis KW - long chain base KW - lung infection KW - Pseudomonas aeruginosa KW - sphingosine Y1 - 2014 U6 - https://doi.org/10.15252/emmm.201404075 SN - 1757-4676 SN - 1757-4684 VL - 6 IS - 9 SP - 1205 EP - 1214 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Pastukhov, Oleksandr A1 - Schwalm, Stephanie A1 - Zangemeister-Wittke, Uwe A1 - Fabbro, Doriano A1 - Bornancin, Frederic A1 - Japtok, Lukasz A1 - Kleuser, Burkhard A1 - Pfeilschifter, Josef A1 - Huwiler, Andrea T1 - The ceramide kinase inhibitor NVP-231 inhibits breast and lung cancer cell proliferation by inducing M phase arrest and subsequent cell death JF - British journal of pharmacology : journal of The British Pharmacological Society N2 - Background and PurposeCeramide kinase (CerK) catalyzes the generation of ceramide-1-phosphate which may regulate various cellular functions, including inflammatory reactions and cell growth. Here, we studied the effect of a recently developed CerK inhibitor, NVP-231, on cancer cell proliferation and viability and investigated the role of cell cycle regulators implicated in these responses. Experimental ApproachThe breast and lung cancer cell lines MCF-7 and NCI-H358 were treated with increasing concentrations of NVP-231 and DNA synthesis, colony formation and cell death were determined. Flow cytometry was performed to analyse cell cycle distribution of cells and Western blot analysis was used to detect changes in cell cycle regulator expression and activation. Key ResultsIn both cell lines, NVP-231 concentration-dependently reduced cell viability, DNA synthesis and colony formation. Moreover it induced apoptosis, as measured by increased DNA fragmentation and caspase-3 and caspase-9 cleavage. Cell cycle analysis revealed that NVP-231 decreased the number of cells in S phase and induced M phase arrest with an increased mitotic index, as determined by increased histone H3 phosphorylation. The effect on the cell cycle was even more pronounced when NVP-231 treatment was combined with staurosporine. Finally, overexpression of CerK protected, whereas down-regulation of CerK with siRNA sensitized, cells for staurosporine-induced apoptosis. Conclusions and ImplicationsOur data demonstrate for the first time a crucial role for CerK in the M phase control in cancer cells and suggest its targeted inhibition, using drugs such as NVP-231, in combination with conventional pro-apoptotic chemotherapy. Y1 - 2014 U6 - https://doi.org/10.1111/bph.12886 SN - 0007-1188 SN - 1476-5381 VL - 171 IS - 24 SP - 5829 EP - 5844 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Neuschaefer-Rube, Frank A1 - Lieske, Stefanie A1 - Kuna, Manuela A1 - Henkel, Janin A1 - Perry, Rachel J. A1 - Erion, Derek M. A1 - Pesta, Dominik A1 - Willmes, Diana M. A1 - Brachs, Sebastian A1 - von Loeffelholz, Christian A1 - Tolkachov, Alexander A1 - Schupp, Michael A1 - Pathe-Neuschaefer-Rube, Andrea A1 - Pfeiffer, Andreas F. H. A1 - Shulman, Gerald I. A1 - Püschel, Gerhard Paul A1 - Birkenfeld, Andreas L. T1 - The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes JF - Diabetes : a journal of the American Diabetes Association Y1 - 2014 SN - 0012-1797 SN - 1939-327X VL - 63 IS - 3 SP - 1048 EP - 1057 PB - American Diabetes Association CY - Alexandria ER - TY - THES A1 - Neumann, Franziska T1 - In vitro-Charakterisierung von TBC1D1 und funktionelle Untersuchung an murinen Inselzellen des Pankreas Y1 - 2014 ER - TY - JOUR A1 - Neuber, Corinna A1 - Schumacher, Fabian A1 - Gulbins, Erich A1 - Kleuser, Burkhard T1 - Method to simultaneously determine the sphingosine 1-phosphate breakdown product (2E)-hexadecenal and its fatty acid derivatives using isotope-dilution HPLC-electrospray ionization-quadrupole/time-of-flight mass spectrometry JF - Analytical chemistry N2 - Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes, can be irreversibly degraded by the membrane-bound S1P lyase (S1PL) yielding (2E)-hexadecenal and phosphoethanolamine. It is discussed that (2E)-hexadecenal is further oxidized to (2E)-hexadecenoic acid by the long-chain fatty aldehyde dehydrogenase ALDH3A2 (also known as FALDH) prior to activation via coupling to coenzyme A (CoA). Inhibition or defects in these enzymes, S1PL or FALDH, result in severe immunological disorders or the Sjogren-Larsson syndrome, respectively. Hence, it is of enormous importance to simultaneously determine the S1P breakdown product (2E)-hexadecenal and its fatty acid metabolites in biological samples. However, no method is available so far. Here, we present a sensitive and selective isotope-dilution high performance liquid chromatographyelectrospray ionizationquadrupole/time-of-flight mass spectrometry method for simultaneous quantification of (2E)-hexadecenal and its fatty acid metabolites following derivatization with 2-diphenylacetyl-1,3-indandione-1-hydrazone and 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. Optimized conditions for sample derivatization, chromatographic separation, and MS/MS detection are presented as well as an extensive method validation. Finally, our method was successfully applied to biological samples. We found that (2E)-hexadecenal is almost quantitatively oxidized to (2E)-hexadecenoic acid, that is further activated as verified by cotreatment of HepG2 cell lysates with (2E)-hexadecenal and the acyl-CoA synthetase inhibitor triacsin C. Moreover, incubations of cell lysates with deuterated (2E)-hexadecenal revealed that no hexadecanoic acid is formed from the aldehyde. Thus, our method provides new insights into the sphingolipid metabolism and will be useful to investigate diseases known for abnormalities in long-chain fatty acid metabolism, e.g., the Sjogren-Larsson syndrome, in more detail. Y1 - 2014 U6 - https://doi.org/10.1021/ac501677y SN - 0003-2700 SN - 1520-6882 VL - 86 IS - 18 SP - 9065 EP - 9073 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Meyer, Sören A1 - Matissek, M. A1 - Mueller, S. M. A1 - Taleshi, M. S. A1 - Ebert, Franziska A1 - Francesconi, Kevin A. A1 - Schwerdtle, Tanja T1 - In vitro toxicological characterisation of three arsenic-containing hydrocarbons JF - Metallomics : integrated biometal science N2 - Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk. Y1 - 2014 U6 - https://doi.org/10.1039/c4mt00061g SN - 1756-5901 SN - 1756-591X VL - 6 IS - 5 SP - 1023 EP - 1033 PB - Royal Society of Chemistry CY - Cambridge ER - TY - THES A1 - Matzke, Daniela T1 - Einfluss des Adipositas-QTL Nob3 auf die Entstehung von Typ-2-Diabetes in schlanken und adipösen Mausmodellen Y1 - 2014 ER - TY - JOUR A1 - Lu, Yong-Ping A1 - Lung, Xu-Jing A1 - Xiao, Xiao-Min A1 - Huang, Si-Min A1 - Liu, Zhi-Wei A1 - Li, Jian A1 - Hocher, Berthold A1 - Chen, You-Peng T1 - Telbivudine during the second and third trimester of pregnancy interrupts HBV intrauterine transmission: a systematic review and meta-analysis JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Beckground: Evaluate the efficacy and safety of telbivudine during the 2nd and 3rd trimester of pregnancy in intrauterine transmission of hepatitis B virus (HBV). Based on the principle of Cochrane systematic reviews, a database was constructed from Medline, EMBASE, Cochrane Library, the US National Science Digital Library (NSDL), the China Biological Medicine Database (CBM-disc), and contact with Chinese experts in the field from November 2006 to February 2013. Results: Either the Mantel-Haenszel or Inverse Variance fixed-effects model or Mantel-Haenszel or Inverse Variance random-effects model was applied for all analyses indicated by odds ratio (OR) and 95% confidence interval (CI). The meta-analysis based on new onset of HBsAg seropositivity of infants at 6 - 12 months postpartum revealed that the control group had an intrauterine transmission rate of 8.25 - 42.31%. This rate was reduced to 0 - 14.29% in the telbivudine treatment group (OR 0.09, 95% CI 0.04 - 0.22, including seven trials, p < 0.001). The rates of intrauterine transmission based on new onset of HBV DNA seropositivity of infants at 6 - 12 months postpartum were 8.25 - 19.23% in the control group and 0 - 3.57% in the treatment group (OR 0.07, 95% CI 0.02 - 0.22, p < 0.001, including only five trials, since two trials had no data on HBV DNA in infants). With the exception of CK elevations, adverse effect frequencies were similar in both groups. Conclusions: Telbivudine is an effective and safe drug for preventing intrauterine transmission of HBV. KW - telbivudine KW - meta-analysis KW - intrauterine KW - transmission of hepatitis B virus (HBV) KW - clinical studies KW - safety efficacy Y1 - 2014 U6 - https://doi.org/10.7754/Clin.Lab.2013.130408 SN - 1433-6510 VL - 60 IS - 4 SP - 571 EP - 586 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Longardt, Ann Carolin A1 - Schmiedchen, B. A1 - Raila, Jens A1 - Schweigert, Florian J. A1 - Obladen, M. A1 - Buehrer, Christoph A1 - Loui, A. T1 - Characterization of the vitamin A transport in preterm infants after repeated high-dose vitamin A injections JF - European journal of clinical nutrition N2 - BACKGROUND/OBJECTIVES: Preterm infants have low vitamin A stores at birth, and parenteral administration of high-dose vitamin A reduces pulmonary morbidity. The aim was to characterize vitamin A transport and status. SUBJECTS/METHODS: Prospective study of 69 preterm infants (median birth weight 995 g, gestational age 28 weeks), in which 51 received 5000 IU vitamin A three times per week intramuscular (i.m.) for 4 weeks and 18 infants without i.m. vitamin A served as controls. Serum retinol, retinyl palmitate, total retinol-binding protein 4 (RBP4), retinol-unbound RBP4 (apo-RBP4) and transthyretin concentrations were determined at days 3 (D3) and 28 (D28) of life. RESULTS: D3 retinol concentrations were low for the entire group (382 (285/531) nmol/l; median/interquartile range) and unrelated to gestational age. D28 retinol was unchanged in controls (382 (280/471) nmol/l), but increased in the vitamin A group (596 (480/825) nmol/l; P < 0.001). A similar pattern was observed for RBP4. The calculated retinol-to-RBP4 ratio rose in vitamin A infants (D3: 0.81 (0.57/0.94), D28: 0.98 (0.77/1.26); P < 0.01) but not in controls. In the vitamin A group, the retinol-to-RBP4 ratio was 41 in 15% of all infants on D3 and in 45% of infants on D28, but was <= 1 in all, but one, controls on D28. CONCLUSIONS: In preterm infants receiving a 4-week course of high-dose i. m. vitamin A, serum retinol concentrations increased by 55%, with molar concentrations of retinol exceeding those of RBP4 in 45% of the infants suggesting transport mechanisms other than RBP4. Y1 - 2014 U6 - https://doi.org/10.1038/ejcn.2014.202 SN - 0954-3007 SN - 1476-5640 VL - 68 IS - 12 SP - 1300 EP - 1304 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Liang, Xu-Jing A1 - Huang, Si-Min A1 - Li, Jian-Ping A1 - Zhu, Xian-Nv A1 - Lu, Yong-Ping A1 - Hocher, Berthold A1 - Chen, You-Peng T1 - Hepatic impairment induced by scrub typhus is associated with new onset of renal dysfunction JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Scrub typhus is a potentially fatal infectious disease caused by Orientia tsutsugamushi. There is little attention given to hepatic impairment in the adults with scrub typhus. This study investigated the incidence and the prognostic implications of hepatic impairment in patients with scrub typhus. Methods: We retrospectively reviewed a total of 143 adult patients with scrub typhus who were admitted between January 1999 and December 2010 in Guangdong province, China. The patients were divided into three groups, e.g., normal, mild, and moderate to severe groups based on the elevated serum ALT and/or total bilirubin levels. Furthermore, clinical characteristics and prognosis of the patient groups were compared. Results: 109 patients (76.2%) had abnormal liver function. Among the patients with hepatic impairment 45 cases (31.4%), 54 cases (37.8%), and 10 cases (7.0%) had mild, moderate, and severe hepatic damage, respectively. The moderate to severe hepatic impairment group had higher levels of serum creatinine compared with that of normal hepatic function. The incidence of new onset of renal dysfunction - defined as peak serum creatinine >= 176 mu mol/L during hospital stay with no evidence of renal disease prior hospitalization - was 0% in the mild hepatic impairment group, 8.9% in the moderate hepatic impairment group, and 21.9% in the severe hepatic impairment group, (p = 0.005 for trend). Additionally, the patients with hepatic impairment (n = 109) had higher incidences of episodes of thrombocytopenia (45.9% vs. 8.82%, p < 0.001), hypoalbuminemia (50.5% vs. 11.8%, p < 0.001), new onset of renal dysfunction (16.5% vs. 0.0%, p = 0.011), and electrocardiogram abnormality (28.4% vs. 8.82%, p = 0.019) than the patients without hepatic impairment. Conclusions: The degree of hepatic impairment induced by scrub typhus is associated with new onset of renal dysfunction. KW - hepatic impairment KW - renal dysfunction KW - complication KW - outcome KW - scrub typhus Y1 - 2014 U6 - https://doi.org/10.7754/Clin.Lab.2013.121203 SN - 1433-6510 VL - 60 IS - 1 SP - 63 EP - 68 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Li, Jian A1 - Chen, You-Peng A1 - Dong, Yun-Peng A1 - Yu, Cal-Hong A1 - Lu, Yong-Ping A1 - Xiao, Xiao-Min A1 - Hocher, Berthold T1 - The impact of umbilical blood flow regulation on fetal development differs in diabetic and non-diabetic pregnancy JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Background/Aims: Diabetes is well-known to influence endothelial function. Endothelial function and blood flow regulation might be different in diabetic and non-diabetic pregnancy. However, the impact of umbilical blood flow regulation in gestational diabetes on fetal development is unknown so far. Methods: In a prospective birth cohort study, we analyzed the association of the umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) and fetal size measures (biparietal diameter, head circumference, abdominal circumference, femur length and birth weight) in 519 non-gestational diabetes mellitus pregnancies (controls) and 226 gestational diabetes mellitus pregnancies in middle (day 160.32 +/- 16.29 of gestation) and late (day 268.12 +/- 13.04 of gestation) pregnancy. Results: Multiple regression analysis considering confounding factors (gestational day of ultrasound examination, offspring sex, maternal body mess index before pregnancy, maternal age at delivery, maternal body weight at delivery and maternal hypertension) showed that umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) were associated with fetal head circumference and femur length in middle gestational diabetes mellitus pregnancy but not in non-gestational diabetes mellitus pregnancy. Head circumference, biparietal diameter, abdominal circumference and femur length in mid gestation were smaller in fetus of gestational diabetes mellitus pregnancy versus non-gestational diabetes mellitus pregnancy. In contrast to non-gestational diabetes mellitus pregnancy in late gestation, umbilical artery Doppler indices in gestational diabetes mellitus pregnancy were not associated with ultrasound measures of fetal growth. Birth weight was slightly increased in gestational diabetes mellitus pregnancy as compared to non-gestational diabetes mellitus pregnancy. Conclusions: The impact of umbilical blood flow on fetal growth is time dependent in human gestational diabetes mellitus and non-gestational diabetes mellitus pregnancy. In gestational diabetes mellitus pregnancy umbilical blood flow is critical for organ development in much earlier stages of pregnancy as compared to non-gestational diabetes mellitus pregnancy. The physiological and molecular pathways why there is a catch up growth in later times of gestational diabetes mellitus pregnancy resulting in larger gestational diabetes mellitus babies at birth needs to be addressed in further studies. KW - Umbilical artery Doppler KW - Blood flow resistance KW - Gestational diabetes mellitus KW - Fetal development Y1 - 2014 U6 - https://doi.org/10.1159/000355815 SN - 1420-4096 SN - 1423-0143 VL - 39 IS - 4 SP - 369 EP - 377 PB - Karger CY - Basel ER - TY - JOUR A1 - Langer, Henning A1 - Carlsohn, Anja T1 - Effects of different dietary proteins and amino acids on skeletal muscle hypertrophy in young adults after resistance exercise: A systematic review JF - Strength and conditioning journal N2 - THIS ARTICLE REVIEWS THE AVAILABLE LITERATURE ON WHICH PROTEINS, AMINO ACIDS, OR COMBINATION OF BOTH SEEM TO BE OPTIMAL TO ENHANCE HYPERTROPHY AFTER RESISTANCE EXERCISE IN YOUNG ADULTS. DEPENDING ON THE CONTENT OF ESSENTIAL AMINO ACIDS AND PARTICULARLY LEUCINE, EITHER AN IMMEDIATE INGESTION OF similar to 20 G MILK PROTEIN FOLLOWED BY A SIMILAR AMOUNT similar to 1 HOUR LATER, OR A SINGLE BOLUS OF similar to 40 G SEEMS TO BE SUITABLE. GREATER AMOUNTS MIGHT BE NECESSARY IF A PROTEIN OF LOWER QUALITY IS CHOSEN ( I. E., PLANT-BASED PROTEINS) TO MATCH THE REQUIRED AMINO ACID QUANTITIES AND FACILITATE MUSCLE GROWTH. Y1 - 2014 SN - 1524-1602 SN - 1533-4295 VL - 36 IS - 3 SP - 33 EP - 42 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - THES A1 - Lang, Iris Scarlett T1 - Fetal programming of growth and metabolism by maternal dietary composition BT - effects of high and low dietary protein:carbohydrate ratios in pregnant primiparous sows Y1 - 2014 ER - TY - THES A1 - Kipp, Anna Patricia T1 - Physiologische und Tumor-Assoziierte Funktionen von Selen und Selenoproteinen Y1 - 2014 ER - TY - JOUR A1 - Keller, Johannes A1 - Catala-Lehnen, Philip A1 - Huebner, Antje K. A1 - Jeschke, Anke A1 - Heckt, Timo A1 - Lueth, Anja A1 - Krause, Matthias A1 - Koehne, Till A1 - Albers, Joachim A1 - Schulze, Jochen A1 - Schilling, Sarah A1 - Haberland, Michael A1 - Denninger, Hannah A1 - Neven, Mona A1 - Hermans-Borgmeyer, Irm A1 - Streichert, Thomas A1 - Breer, Stefan A1 - Barvencik, Florian A1 - Levkau, Bodo A1 - Rathkolb, Birgit A1 - Wolf, Eckhard A1 - Calzada-Wack, Julia A1 - Neff, Frauke A1 - Gailus-Durner, Valerie A1 - Fuchs, Helmut A1 - de Angelis, Martin Hrabe A1 - Klutmann, Susanne A1 - Tsourdi, Elena A1 - Hofbauer, Lorenz C. A1 - Kleuser, Burkhard A1 - Chun, Jerold A1 - Schinke, Thorsten A1 - Amling, Michael T1 - Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts JF - Nature Communications N2 - The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signalling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P(3). Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, but not in S1P(3)-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts. Y1 - 2014 U6 - https://doi.org/10.1038/ncomms6215 SN - 2041-1723 VL - 5 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Katsuno, Tsuyoshi A1 - Kasuga, Hisae A1 - Kusano, Yumi A1 - Yaguchi, Yoshihiro A1 - Tomomura, Miho A1 - Cui, Jilai A1 - Yang, Ziyin A1 - Baldermann, Susanne A1 - Nakamura, Yoriyuki A1 - Ohnishi, Toshiyuki A1 - Mase, Nobuyuki A1 - Watanabe, Naoharu T1 - Characterisation of odorant compounds and their biochemical formation in green tea with a low temperature storage process JF - Food chemistry N2 - We produced low temperature (15 degrees C) processed green tea (LTPGT) with higher aroma contents than normal green tea (Sencha). Normal temperature processed green tea (NTPGT), involved storing at 25 degrees C, and Sencha had no storing process. Sensory evaluation showed LTPGT had higher levels of floral and sweet odorants than NTPGT and Sencha. Aroma extract dilution analysis and gas chromatography-mass spectrometry-olfactometry indicated LTPGT had 12 aroma compounds with high factor dilution values (FD). Amongst LTPGT's 12 compounds, indole, jasmine lactone, cis-jasmone, coumarin, and methyl epijasmonate contributed to floral, fruity and sweet characters. In particular, indole increased initially, peaking at 16 h, then gradually decreased; Feeding experiments suggested [N-15]indole and [N-15]oxygenated indoles (OX-indoles) were produced from [N-15]anthranilic acid. We proposed the increase in indole was due to transformation of anthranilic acid during the 16 h storage and the subsequent decline in indole level was due to its conversion to OX-indoles. KW - Odorant compounds KW - Camellia sinensis KW - Tea leaves KW - Indole KW - [N-15]Indole KW - [N-15]Anthranilic acid KW - Metabolome analysis Y1 - 2014 U6 - https://doi.org/10.1016/j.foodchem.2013.10.069 SN - 0308-8146 SN - 1873-7072 VL - 148 SP - 388 EP - 395 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Imeri, Faik A1 - Fallegger, Daniel A1 - Zivkovic, Aleksandra A1 - Schwalm, Stephanie A1 - Enzmann, Gaby A1 - Blankenbach, Kira A1 - Heringdorf, Dagmar Meyer Zu A1 - Homann, Thomas A1 - Kleuser, Burkhard A1 - Pfeilschifter, Josef A1 - Engelhardt, Britta A1 - Stark, Holger A1 - Huwiler, Andrea T1 - Novel oxazolo-oxazole derivatives of FTY720 reduce endothelial cell permeability, immune cell chemotaxis and symptoms of experimental autoimmune encephalomyelitis in mice JF - Neuropharmacology N2 - The immunomodulatory FTY720 (fingolimod) is presently approved for the treatment of relapsing-remitting multiple sclerosis. It is a prodrug that acts by modulating sphingosine 1-phosphate (S1P) receptor signaling. In this study, we have developed and characterized two novel oxazolo-oxazole derivatives of FTY720, ST-968 and the oxy analog ST-1071, which require no preceding activating phosphorylation, and proved to be active in intact cells and triggered S1P(1) and S1P(3), but not S1P(2), receptor internalization as a result of receptor activation. Functionally, ST-968 and ST-1071 acted similar to FTY720 to abrogate S1P-triggered chemotaxis of mouse splenocytes, mouse T cells and human U937 cells, and reduced TNFa- and LPS-stimulated endothelial cell permeability. The compounds also reduced TNF alpha-induced ICAM-1 and VCAM-1 mRNA expression, but restored TNF alpha-mediated downregulation of PECAM-1 mRNA expression. In an in vivo setting, the application of ST-968 or ST-1071 to mice resulted in a reduction of blood lymphocytes and significantly reduced the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice comparable to FTY720 either by prophylactic or therapeutic treatment. In parallel to the reduced clinical symptoms, infiltration of immune cells in the brain was strongly reduced, and in isolated tissues of brain and spinal cord, the mRNA and protein expressions of ICAM-1 and VCAM-1, as well as of matrix metalloproteinase-9 were reduced by all compounds, whereas PECAM-1 and tissue inhibitor of metalloproteinase TIMP-1 were upregulated. In summary, the data suggest that these novel butterfly derivatives of FTY720 could have considerable implication for future therapies of multiple sclerosis and other autoimmune diseases. (C) 2014 Elsevier Ltd. All rights reserved. KW - Fingolimod KW - ST-968 KW - ST-1071 KW - Sphingosine 1-phosphate KW - Endothelial cells KW - Permeability KW - Multiple sclerosis Y1 - 2014 U6 - https://doi.org/10.1016/j.neuropharm.2014.05.012 SN - 0028-3908 SN - 1873-7064 VL - 85 SP - 314 EP - 327 PB - Elsevier CY - Oxford ER - TY - THES A1 - Hüttl, Christine T1 - Synthese und Charakterisierung von multivalenten peptidbasierten Liganden als biomolekulare Erkennunngseinheit für Influenzaviren Y1 - 2014 CY - Potsdam ER - TY - CHAP A1 - Hocher, Berthold A1 - Reichetzeder, Christoph A1 - von Websky, Karoline A1 - Tsuprykov, Oleg A1 - Klein, T. T1 - Dipeptidyl peptidase-4 inhibition in a rat model of ischaemia-reperfusion injury may accelerate tubular regeneration but does not improve glomerular filtration rate T2 - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) Y1 - 2014 SN - 0012-186X SN - 1432-0428 VL - 57 SP - S538 EP - S538 PB - Springer CY - New York ER - TY - JOUR A1 - Hocher, Berthold T1 - More than genes: the advanced fetal programming hypothesis JF - Journal of reproductive immunology : the international journal for experimental and clinical reproductive immunobiology N2 - Many lines of data, initial epidemiologic studies as well as subsequent extensive experimental studies, indicate that early-life events play a powerful role in influencing later suceptibility to certain chronic diseases. Such events might be over- or undernutrition, exposure to environmental toxins, but also changes in hormones, in particular stress hormones. Typically, those events are triggered by the environmental challenges of the mother. However, recent studies have shown that paternal environmental or nutritional factors affect the phenotype of the offspring as well. The maternal and paternal environmental factors act on the phenotype of the offspring via epigenetic modification of its genome. The advanced fetal programming hypothesis proposes an additional non-environmentally driven mechanism: maternal and also paternal genes may influence the maturating sperm, the oocyte, and later the embryo/fetus, leading to their epigenetic alteration. Thus, the observed phenotype of the offspring may be altered by maternal/paternal genes independent of the fetal genome. Meanwhile, several independent association studies in humans dealing with metabolic and neurological traits also suggest that maternal genes might affect the offspring phenotype independent of the transmission of that particular gene to the offspring. Considering the implications of this hypothesis, some conclusions drawn from transgenic or knockout animal models and based on the causality between a genetic alteration and a phenotype, need to be challenged. Possible implications for the development, diagnostic and therapy of human genetic diseases have to be investigated. (C) 2014 Elsevier Ireland Ltd. All rights reserved. KW - Fetal programming KW - Advanced fetal programming hypothesis Y1 - 2014 U6 - https://doi.org/10.1016/j.jri.2014.03.001 SN - 0165-0378 VL - 104 SP - 8 EP - 11 PB - Elsevier CY - Clare ER - TY - JOUR A1 - Heunisch, Fabian A1 - von Einem, Gina A1 - Alter, Markus L. A1 - Weist, Andreas A1 - Dschietzig, Thomas A1 - Kretschmer, Axel A1 - Hocher, Berthold T1 - Urinary ET-1 excretion after exposure to radio-contrast media in diabetic patients and patients with preexisting mild impaired renal function JF - Life sciences : molecular, cellular and functional basis of therapy N2 - Aims: Contrast media-induced nephropathy (CIN) is associated with increased morbidity and mortality. The renal endothelin system has been associated with disease progression of various acute and chronic renal diseases. However, robust data coming from adequately powered prospective clinical studies analyzing the short and long-term impacts of the renal ET system in patients with CIN are missing so far. We thus performed a prospective study addressing this topic. Main methods: We included 327 patients with diabetes or renal impairment undergoing coronary angiography. Blood and spot urine were collected before and 24 h after contrast media (CM) application. Patients were followed for 90 days for major clinical events like need for dialysis, unplanned rehospitalization or death. Key findings: The concentration of ET-1 and the urinary ET-1/creatinine ratio decreased in spot urine after CM application (ET-1 concentration: 0.91 +/- 1.23pg/ml versus 0.63 +/- 1.03pg/ml, p<0.001; ET-1/creatinine ratio: 0.14 +/- 0.23 versus 0.09 +/- 0.19, p<0.001). The urinary ET-1 concentrations in patients with CIN decreased significantly more than in patients without CIN (-0.26 +/- 1.42pg/ml vs. -0.79 +/- 1.69pg/ml, p=0.041), whereas the decrease of the urinary ET-1/creatinine ratio was not significantly different (non-CIN patients: -0.05 +/- 0.30; CIN patients: -0.11 +/- 0.21, p=0.223). Urinary ET-1 concentrations as well as the urinary ET-1/creatinine ratio were not associated with clinical events (need for dialysis, rehospitalization or death) during the 90day follow-up after contrast media exposure. However, the urinary ET-1 concentration and the urinary ET-1/creatinine ratio after CM application were higher in those patients who had a decrease of GFR of at least 25% after 90days of follow-up. Significance: In general the ET-1 system in the kidney seems to be down-regulated after contrast media application in patients with moderate CIN risk. Major long-term complications of CIN (need for dialysis, rehospitalization or death) are not associated with the renal ET system. (C) 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. KW - Urinary ET-1 KW - Clinical study KW - Radiocontrast media-induced nephropathy KW - Kidney Y1 - 2014 U6 - https://doi.org/10.1016/j.lfs.2013.12.233 SN - 0024-3205 SN - 1879-0631 VL - 118 IS - 2 SP - 440 EP - 445 PB - Elsevier CY - Oxford ER - TY - CHAP A1 - Henkel, Janine A1 - Camargo, Rodolfo Gonzalez A1 - Schanze, Nancy A1 - Püschel, Gerhard Paul T1 - The vicious circle of prostaglandin- and cytokine-dependent hepatic insulin resistance: a key role of prostaglandin E2 T2 - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) Y1 - 2014 SN - 0012-186X SN - 1432-0428 VL - 57 SP - S241 EP - S242 PB - Springer CY - New York ER - TY - JOUR A1 - Goetz, Klaus-Peter A1 - Chmielewski, Frank M. A1 - Homann, Thomas A1 - Huschek, Gerd A1 - Matzneller, Philipp A1 - Rawel, Harshadrai Manilal T1 - Seasonal changes of physiological parameters in sweet cherry (Prunus avium L.) buds JF - Scientia horticulturae : an international journal sponsored by the International Society for Horticultural Science N2 - The transition from dormant stage to the beginning of growth was first obvious by markedly changes of the water content. The phase from green tip to tight cluster, with a length of only 4 days, was the period of the most physiological activity in single buds, because of the highest daily accumulation rates of fresh/dry weight, C, N. We assume a concentration dependant regulation of the member of the aspartate family (asparagine, aspartic acid, isoleucine) during dormancy, growth and development in sweet cherry buds. The ABA content showed 2011/12 a clear bimodal pattern which was at lower level similar in 2012/13, but not so strong incisive. In both years, the first peak was probably related to the end of endodormancy. However the ABA-isomer content showed in both seasons a unimodal pattern. The maximum of the ratio of ABA-isomer/ABA indicated the beginning of ontogenetic development which starts 3 and 2 weeks later, respectively. Our results suggest that ABA and the ABA-isomer in the sweet cherry buds regulate differentiated metabolic processes in the dormant stage and during bud growth and development. After replication in the season 2013/14 the estimated dates of release of endodormancy, beginning of ecodormancy and start of ontogenetic development will be used to validate and improve phenological models for the beginning of cherry blossom. (C) 2014 Elsevier B.V. All rights reserved. KW - Abscisic acid KW - Amino acids KW - Dormancy KW - Flower buds KW - Phenological modelling KW - Prunus avium L. Y1 - 2014 U6 - https://doi.org/10.1016/j.scienta.2014.04.012 SN - 0304-4238 SN - 1879-1018 VL - 172 SP - 183 EP - 190 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Fromm, Sabine A1 - Beisswanger, Elena A1 - Kaebohrer, Annemarie A1 - Tenhagen, Bernd-Alois T1 - Risk factors for MRSA in fattening pig herds - A meta-analysis using pooled data JF - Preventive veterinary medicine : an international journal on research and development in veterinary epidemiology, animal disease prevention and control, and animal health economics N2 - The importance of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) as an infectious agent for humans has increased in recent years in Germany. Although it is well known that the prevalence of MRSA in pig farms is high, risk factors for the presence of MRSA in herds of fattening pigs are still poorly understood. The aim of this study was to evaluate available data from previous studies on MRSA in fattening pigs in a meta-analysis to answer the question: What are the factors associated with the occurrence of MRSA in fattening pig herds? The studies on MRSA in pigs that were identified by literature research were heterogeneous with respect to the risk factors investigated and the type of herds focused on. Therefore we decided to carry out a pooling analysis on herd level rather than a typical meta-analysis. Eligible herd data were identified based on the published literature and communication with the authors. The final data set covered 400 fattening pig herds from 10 different studies and 12 risk factors. The prevalence of MRSA in the 400 fattening pig herds was 53.5%. Data were analyzed using generalized estimating equations (GEE). The resulting multi-variate model confirmed previously identified risk factors for MRSA in pig herds (herd size and herd type). It also identified further risk factors: group treatment of fattening pigs with antimicrobial drugs (OR=1.79) and housing fattening pig herds on at least partially slatted floors (OR=2.39) compared to plain floor. In contrast, according to the model, fattening pig herds on farms keeping other livestock along with pigs were less likely to harbor MRSA (OR=0.54). The results underline the benefits from a pooling analysis and cooperative re-evaluation of published data. (C) 2014 The Authors. Published by Elsevier B.V. KW - Fattening pigs KW - Swine KW - MRSA KW - Methicillin resistant Staphylococcus aureus KW - Risk factor KW - Meta-analysis KW - Pooling analysis KW - Herd size KW - Herd type KW - Antimicrobial drugs KW - Slatted floor KW - Other livestock KW - Zoonoses Y1 - 2014 U6 - https://doi.org/10.1016/j.prevetmed.2014.08.014 SN - 0167-5877 SN - 1873-1716 VL - 117 IS - 1 SP - 180 EP - 188 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Frede, Katja A1 - Henze, Andrea A1 - Khalil, Mahmoud A1 - Baldermann, Susanne A1 - Schweigert, Florian J. A1 - Rawel, Harshadrai Manilal T1 - Stability and cellular uptake of lutein-loaded emulsions JF - Journal of functional food N2 - The carotenoid lutein can improve human health. Since only a fraction is absorbed from food, lutein supplementation might be recommended. Emulsions could be good carrier systems to improve the bioavailability of lutein. Six different emulsifier compositions were used in this study to prepare lutein-loaded emulsions: beta-lactoglobulin, beta-lactoglobulin/lecithin, Biozate 1, Biozate 1/lecithin, Been 20 and Tween 20/lecithin. The droplet size, resistance to creaming, lutein stability, cytotoxicity and lutein uptake by HT29 cells were investigated. The whey protein beta-lactoglobulin, the whey protein hydrolysate Biozate 1 and the combination with lecithin brought the most promising results. The small droplet sizes and resistance to creaming were an indication of physical stable emulsions. Furthermore, these emulsifiers prevented oxidation of lutein. The choice of emulsifier had a strong impact on the uptake by HT29 cells. The highest lutein absorption was observed with the combination of Biozate 1 and lecithin. KW - Lutein KW - Emulsion KW - Whey protein KW - Stability KW - Bioavailability Y1 - 2014 U6 - https://doi.org/10.1016/j.jff.2014.03.011 SN - 1756-4646 VL - 8 SP - 118 EP - 127 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Fayyaz, Susann A1 - Japtok, Lukasz A1 - Kleuser, Burkhard T1 - Divergent role of sphingosine 1-Phosphate on insulin resistance JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Insulin resistance is a complex metabolic disorder in which insulin-sensitive tissues fail to respond to the physiological action of insulin. There is a strong correlation of insulin resistance and the development of type 2 diabetes both reaching epidemic proportions. Dysfunctional lipid metabolism is a hallmark of insulin resistance and a risk factor for several cardiovascular and metabolic disorders. Numerous studies in humans and rodents have shown that insulin resistance is associated with elevations of non-esterified fatty acids (NEFA) in the plasma. Moreover, bioactive lipid intermediates such as diacylglycerol (DAG) and ceramides appear to accumulate in response to NEFA, which may interact with insulin signaling. However, recent work has also indicated that sphingosine 1-phosphate (S1P), a breakdown product of ceramide, modulate insulin signaling in different cell types. In this review, we summarize the current state of knowledge about S1P and insulin signaling in insulin sensitive cells. A specific focus is put on the action of S1P on hepatocytes, pancreatic beta-cells and skeletal muscle cells. In particular, modulation of S1P-signaling can be considered as a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. KW - Sphingosine 1-phosphate (S1P) KW - Insulin resistance KW - Ceramides KW - Diacylglycerol (DAG) KW - Non-esterified fatty acids (NEFA) KW - Hepatocytes KW - Pancreatic cells KW - Skeletal muscle cells Y1 - 2014 U6 - https://doi.org/10.1159/000362990 SN - 1015-8987 SN - 1421-9778 VL - 34 IS - 1 SP - 134 EP - 147 PB - Karger CY - Basel ER - TY - JOUR A1 - Fayyaz, Susann A1 - Henkel, Janin A1 - Japtok, Lukasz A1 - Krämer, Stephanie A1 - Damm, Georg A1 - Seehofer, Daniel A1 - Püschel, Gerhard Paul A1 - Kleuser, Burkhard T1 - Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of hepatocytes via the S1P(2) receptor subtype JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Enhanced plasma levels of NEFA have been shown to induce hepatic insulin resistance, which contributes to the development of type 2 diabetes. Indeed, sphingolipids can be formed via a de novo pathway from the saturated fatty acid palmitate and the amino acid serine. Besides ceramides, sphingosine 1-phosphate (S1P) has been identified as a major bioactive lipid mediator. Therefore, our aim was to investigate the generation and function of S1P in hepatic insulin resistance. The incorporation of palmitate into sphingolipids was performed by rapid-resolution liquid chromatography-MS/MS in primary human and rat hepatocytes. The influence of S1P and the involvement of S1P receptors in hepatic insulin resistance was examined in human and rat hepatocytes, as well as in New Zealand obese (NZO) mice. Palmitate induced an impressive formation of extra- and intracellular S1P in rat and human hepatocytes. An elevation of hepatic S1P levels was observed in NZO mice fed a high-fat diet. Once generated, S1P was able, similarly to palmitate, to counteract insulin signalling. The inhibitory effect of S1P was abolished in the presence of the S1P(2) receptor antagonist JTE-013 both in vitro and in vivo. In agreement with this, the immunomodulator FTY720-phosphate, which binds to all S1P receptors except S1P(2), was not able to inhibit insulin signalling. These data indicate that palmitate is metabolised by hepatocytes to S1P, which acts via stimulation of the S1P(2) receptor to impair insulin signalling. In particular, S1P(2) inhibition could be considered as a novel therapeutic target for the treatment of insulin resistance. KW - FTY720 KW - Insulin signalling KW - Palmitate KW - S1P receptors KW - Sphingolipids KW - Sphingosine 1-phosphate Y1 - 2014 U6 - https://doi.org/10.1007/s00125-013-3123-6 SN - 0012-186X SN - 1432-0428 VL - 57 IS - 2 SP - 373 EP - 382 PB - Springer CY - New York ER - TY - JOUR A1 - Draude, F. A1 - Pelster, A. A1 - Koersgen, M. A1 - Kassenboehmer, R. A1 - Schwerdtle, Tanja A1 - Muething, J. A1 - Arlinghaus, H. F. T1 - ToF-SIMS imaging of plasma membrane lipids with sub-micrometer resolution JF - Surface and interface analysis : an international journal devoted to the development and application of techniques for the analysis surfaces, interfaces and thin films N2 - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for label-free analyses of the molecular lateral distribution of two different epithelial cell membranes (PANC-1 and UROtsa). The goal of the research was to enhance the ion yield of specific membrane molecules for improving the membrane imaging capability of ToF-SIMS on the nanoscale lateral dimension. For this task, a special silicon wafer sandwich preparation technique was optimized using different wafer materials, spacers, and washing procedures. Under optimized preparation conditions, the yield could be significantly enhanced, allowing imaging of the inhomogeneous distribution of phosphocholine (common head group for phosphatidylcholine and sphingomyelin) of a PANC-1 cell membrane's outer lipid layer with a lateral resolution of less than 200nm. Copyright (c) 2014 John Wiley & Sons, Ltd. KW - ToF-SIMS KW - high-resolution imaging KW - membrane analysis KW - lipid analysis KW - yield enhancement KW - sample preparation Y1 - 2014 U6 - https://doi.org/10.1002/sia.5576 SN - 0142-2421 SN - 1096-9918 VL - 46 SP - 127 EP - 130 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Cramer, Sandra A1 - Tacke, Sebastian A1 - Bornhorst, Julia A1 - Klingauf, Jürgen A1 - Schwerdtle, Tanja A1 - Galla, Hans-Joachim T1 - The Influence of Silver Nanoparticles on the Blood-Brain and the Blood-Cerebrospinal Fluid Barrier in vitro JF - Journal of Nanomedicine & Nanotechnology N2 - The use of silver nanoparticles in medical and consumer products such as wound dressings, clothing and cosmetic has increased significantly in recent years. Still, the influence of these particles on our health and especially on our brain, has not been examined adequately up to now. We studied the influence of AgEO- (Ethylene Oxide) and AgCitrate-Nanoparticles (NPs) on the protective barriers of the brain, namely the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (blood-CSF) barrier in vitro. The NPs toxicity was evaluated by examining changes in membrane integrity, cell morphology, barrier properties, oxidative stress and inflammatory reactions. AgNPs decreased cell viability, disturbed barrier integrity and tight junctions and triggered oxidative stress and DNA strand breaks. However, all mentioned effects were, at least partly, suppressed by a Citrate-coating and were most pronounced in the cells of the BBB as compared to the epithelial cells representing the blood-CSF barrier. AgEO- but not AgCitrate-NPs also triggered an inflammatory reaction in porcine brain capillary endothelial cells (PBCEC), which represent the BBB. Our data indicate that AgNPs may cause adverse effects within the barriers of the brain, but their toxicity can be reduced by choosing an appropriate coating material. Y1 - 2014 U6 - https://doi.org/10.4172/2157-7439.1000225 SN - 2157-7439 VL - 5 IS - 5 ER - TY - JOUR A1 - Cosme, Marco A1 - Franken, Philipp A1 - Mewis, Inga A1 - Baldermann, Susanne A1 - Wurst, Susanne T1 - Arbuscular mycorrhizal fungi affect glucosinolate and mineral element composition in leaves of Moringa oleifera JF - Mycorrhiza N2 - Moringa is a mycorrhizal crop cultivated in the tropics and subtropics and appreciated for its nutritive and health-promoting value. As well as improving plant mineral nutrition, arbuscular mycorrhizal fungi (AMF) can affect plant synthesis of compounds bioactive against chronic diseases in humans. Rhizophagus intraradices and Funneliformis mosseae were used in a full factorial experiment to investigate the impact of AMF on the accumulation of glucosinolates, flavonoids, phenolic acids, carotenoids, and mineral elements in moringa leaves. Levels of glucosinolates were enhanced, flavonoids and phenolic acids were not affected, levels of carotenoids (including provitamin A) were species-specifically reduced, and mineral elements were affected differently, with only Cu and Zn being increased by the AMF. This study presents novel results on AMF effects on glucosinolates in leaves and supports conclusions that the impacts of these fungi on microelement concentrations in edible plants are species dependent. The nonspecific positive effects on glucosinolates and the species-specific negative effects on carotenoids encourage research on other AMF species to achieve general benefits on bioactive compounds in moringa. KW - Arbuscularmycorrhizal fungi KW - Moringa oleifera KW - Crop quality KW - Health-promoting compounds KW - Microelements Y1 - 2014 U6 - https://doi.org/10.1007/s00572-014-0574-7 SN - 0940-6360 SN - 1432-1890 VL - 24 IS - 7 SP - 565 EP - 570 PB - Springer CY - New York ER -