@article{GroopCooperPerkovicetal.2017, author = {Groop, Per-Henrik and Cooper, Mark E. and Perkovic, Vlado and Hocher, Berthold and Kanasaki, Keizo and Haneda, Masakazu and Schernthaner, Guntram and Sharma, Kumar and Stanton, Robert C. and Toto, Robert and Cescutti, Jessica and Gordat, Maud and Meinicke, Thomas and Koitka-Weber, Audrey and Thiemann, Sandra and von Eynatten, Maximilian}, title = {Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction}, series = {Diabetes obesity \& metabolism : a journal of pharmacology and therapeutics}, volume = {19}, journal = {Diabetes obesity \& metabolism : a journal of pharmacology and therapeutics}, number = {11}, publisher = {Wiley}, address = {Hoboken}, issn = {1462-8902}, doi = {10.1111/dom.13041}, pages = {1610 -- 1619}, year = {2017}, abstract = {Aims: The MARLINA-T2D study (ClinicalTrials. gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. Methods: A total of 360 individuals with type 2 diabetes, HbA1c 6.5\% to 10.0\% (48-86 mmol/ mol), estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m(2) and urinary albumin-tocreatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time-weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8\% +/- 0.9\% (62.2 +/- 9.6 mmol/mol) and 126 mg/g, respectively; 73.7\% and 20.3\% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60\% (-6.6 mmol/mol) (95\% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7 mmol/mol]; P <.0001). The placebo-adjusted gMean for time-weighted average of percentage change in UACR from baseline was -6.0\% (95\% CI, -15.0 to 3.0; P =.1954). The adverse-event profile, including renal safety and change in eGFR, was similar between the linagliptin and placebo groups. Conclusions: In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo-adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.}, language = {en} } @misc{HocherTsuprykov2017, author = {Hocher, Berthold and Tsuprykov, Oleg}, title = {Renoprotective effects of GLP1R agonists and SGLT2 inhibitors}, series = {Nature reviews nephroloy}, volume = {13}, journal = {Nature reviews nephroloy}, publisher = {Nature Publ. Group}, address = {New York}, issn = {1759-5061}, doi = {10.1038/nrneph.2017.140}, pages = {728 -- 729}, year = {2017}, abstract = {New data from the LEADER trial show that the glucagon-like peptide 1 receptor agonist liraglutide protects against diabetic nephropathy in patients with type 2 diabetes mellitus. The renoprotective efficacy of liraglutide is not, however, as great as that reported for the sodium-glucose cotransporter 2 inhibitor emplagiflozin in the EMPA-REG OUTCOME trial.}, language = {en} } @article{StrehlauWeberLuerenbaumetal.2017, author = {Strehlau, Jenny and Weber, Till and Luerenbaum, Constantin and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja and Winter, Martin and Nowak, Sascha}, title = {Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials}, series = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica}, volume = {409}, journal = {Analytical and bioanalytical chemistry : a merger of Fresenius' journal of analytical chemistry, Analusis and Quimica analitica}, publisher = {Springer}, address = {Heidelberg}, issn = {1618-2642}, doi = {10.1007/s00216-017-0549-6}, pages = {6123 -- 6131}, year = {2017}, abstract = {A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5-12.9\%. It could be shown that no matrix effects were present and recovery rates between 98 and 104\% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place.}, language = {en} } @article{WittEbertMeyeretal.2017, author = {Witt, Barbara and Ebert, Franziska and Meyer, S{\"o}ren and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons}, series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, volume = {61}, journal = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology}, publisher = {Wiley}, address = {Hoboken}, issn = {1613-4125}, doi = {10.1002/mnfr.201700199}, pages = {10}, year = {2017}, abstract = {Scope: In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Methods and results: Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA(V)) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA(V) were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. Conclusion: These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment.}, language = {en} } @article{GoetzChmielewskiGoedekeetal.2017, author = {Goetz, Klaus-Peter and Chmielewski, Frank M. and Goedeke, Kristin and Wolf, Kristine and Jander, Elisabeth and Sievers, Steven and Homann, Thomas and Huschek, Gerd and Rawel, Harshadrai Manilal}, title = {Assessment of amino acids during winter rest and ontogenetic development in sweet cherry buds (Prunus avium. L.)}, series = {Scientia horticulturae : an international journal sponsored by the International Society for Horticultural Science}, volume = {222}, journal = {Scientia horticulturae : an international journal sponsored by the International Society for Horticultural Science}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0304-4238}, doi = {10.1016/j.scienta.2017.05.001}, pages = {102 -- 110}, year = {2017}, abstract = {This study examined changes in sweet cherry buds of 'Summit' cultivar in four seasons (2011/12-2014/15) with respect to the nitrogen (N) content and the profile of eight free amino acids (asparagine (Asn), aspartic acid (Asp), isoleucine (Ile), glutamine (Gln), glutamic acid (Glu), arginine (Arg), alanine (Ala), histidine (His)). The presented results are to our knowledge the first under natural conditions in fruit tree orchards with a high temporal resolution from the dormant stage until cluster development. The N content in the buds from October, during endo- and ecodormancy until the beginning of ontogenetic development was a relatively stable parameter in each of the four seasons. The N accumulation into the buds began after 'swollen bud' and significant differences were visible at 'green tip' with an N content of 3.24, 3.12, 3.08, 2.40 which increased markedly to the mean of 'tight' and 'open cluster' by 3.77\%, 3.78\%, 3.44\% and 3.10\% in 2012-2015, respectively. In the buds, levels of asparagine were higher (up to 44 mg g\&\#8722;1 DW\&\#8722;1) than aspartic acid (up to 2 mg g\&\#8722;1 DW\&\#8722;1) and aspartic acid higher than isoleucine (up to 0.83 mg g\&\#8722;1 DW\&\#8722;1). Levels of glutamine were higher (up to 25 mg g\&\#8722;1 DW\&\#8722;1) than glutamic acid (up to 20 mg g\&\#8722;1 DW\&\#8722;1). The course of the arginine content was higher in 2011/12 compared to 2012/13, 2013/14 and 2014/15 which showed only slight differences. The alanine content in the buds was denoted in the four seasons only by relatively minor changes. The histidine content was higher in 2011/12 and 2012/13 compared to 2013/14 and 2014/15 which showed a comparable pattern. For 6 amino acids (Asn, Asp, Ile, Glu, Arg, Ala), the highest content was observed in 2012/13, the warmest period between swollen bud and open cluster. However in 2014/15, the season with the lowest mean temperature of 8.8 °C, only the content of Gln was the lowest. It was not possible to explain any seasonal differences in the amino acid content by environmental factors (air temperature) on the basis of few seasons. From none of the measured free amino acids could a clear determination of the date of endodormancy release (t1) or the beginning of the ontogenetic development (t1*) be derived. Therefore, these amino acids are no suitable markers to improve phenological models for the beginning of cherry blossom.}, language = {en} } @article{WittMeyerEbertetal.2017, author = {Witt, Barbara and Meyer, S{\"o}ren and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja}, title = {Toxicity of two classes of arsenolipids and their water-soluble metabolites in human differentiated neurons}, series = {Archives of toxicology : official journal of EUROTOX}, volume = {91}, journal = {Archives of toxicology : official journal of EUROTOX}, publisher = {Springer}, address = {Heidelberg}, issn = {0340-5761}, doi = {10.1007/s00204-017-1933-x}, pages = {3121 -- 3134}, year = {2017}, abstract = {Arsenolipids are lipid-soluble organoarsenic compounds, mainly occurring in marine organisms, with arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) representing two major subgroups. Recently, toxicity studies of several arsenolipids showed a high cytotoxic potential of those arsenolipids in human liver and bladder cells. Furthermore, feeding studies with Drosophila melanogaster indicated an accumulation of arsenolipids in the fruit fly's brain. In this study, the neurotoxic potential of three AsHCs, two AsFAs and three metabolites (dimethylarsinic acid, thio/oxo-dimethylarsenopropanoic acid) was investigated in comparison to the toxic reference arsenite (iAsIII) in fully differentiated human brain cells (LUHMES cells). Thereby, in the case of AsHCs both the cell number and cell viability were reduced in a low micromolar concentration range comparable to iAsIII, while AsFAs and the applied metabolites were less toxic. Mechanistic studies revealed that AsHCs reduced the mitochondrial membrane potential, whereas neither iAsIII nor AsFAs had an impact. Furthermore, neurotoxic mechanisms were investigated by examining the neuronal network. Here, AsHCs massively disturbed the neuronal network and induced apoptotic effects, while iAsIII and AsFAs showed comparatively lesser effects. Taking into account the substantial in vitro neurotoxic potential of the AsHCs and the fact that they could transfer across the physiological barriers of the brain, a neurotoxic potential in vivo for the AsHCs cannot be excluded and needs to be urgently characterized.}, language = {en} } @article{ErbersdoblerBarthJahreis2017, author = {Erbersdobler, Helmut F. and Barth, Christian A. and Jahreis, Gerhard}, title = {K{\"o}rnerleguminosen in der Humanern{\"a}hrung}, series = {Ern{\"a}hrungs-Umschau : Forschung \& Praxis}, volume = {64}, journal = {Ern{\"a}hrungs-Umschau : Forschung \& Praxis}, number = {10}, publisher = {Umschau-Zeitschriftenverl.}, address = {Frankfurt, Main}, issn = {0174-0008}, doi = {10.4455.eu.2017.034}, pages = {140 -- 144}, year = {2017}, abstract = {Fortsetzung aus Ern{\"a}hrungs Umschau Heft 9/2017 Fetts{\"a}urenverteilung Die Gehalte an den wichtigsten Fetts{\"a}uren (FS) sind in • Tabelle 4 und 5 aufgef{\"u}hrt, in g/100 g sowie in Prozent des Fettanteils (Etherextrakt bzw. g FS-Methylester pro 100 g der Summe der FS-Methylester). Erbsen und Ackerbohnen spielen als Fett- und FS-Quelle praktisch keine Rolle. Sojabohnen sind eine wesentliche Quelle f{\"u}r Linols{\"a}ure, die h{\"a}ufigste n-6-FS. An zweiter Stelle steht die {\"O}ls{\"a}ure. Aber auch der Gehalt an der n-3-FS α-Linolens{\"a}ure (ALA) ist hoch, womit sich Soja{\"o}l in die Reihe der Fette mit mittlerem ALA-Gehalt, wie Raps- und Walnuss{\"o}l einreiht. Im Gegensatz zu Raps{\"o}l entspricht jedoch das Linols{\"a}ure/α-Linolens{\"a}ure- Verh{\"a}ltnis nicht dem empfohlenen Verh{\"a}ltnis von 5:1 in der Gesamt- Di{\"a}t [13]. Zum Ausgleich f{\"u}r die Fette aus der {\"u}brigen Nahrung (Getreide, Lebensmittel tierischer Herkunft) sollten Pflanzen{\"o}le besser noch ein engeres Verh{\"a}ltnis als 5:1 aufweisen. Das trifft f{\"u}r Lupinen-{\"O}l schon eher zu, wenngleich der absolute Beitrag an ALA hier eher gering ist.}, language = {de} } @misc{ReichetzederHocher2017, author = {Reichetzeder, Christoph and Hocher, Berthold}, title = {DPP4 inhibition prevents AKI}, series = {Oncotarget}, volume = {8}, journal = {Oncotarget}, publisher = {Impact Journals LLC}, address = {Orchard Park}, issn = {1949-2553}, doi = {10.18632/oncotarget.20212}, pages = {64655 -- 64656}, year = {2017}, language = {en} } @article{AuyyuenyongHenzeUngruetal.2017, author = {Auyyuenyong, Ratchada and Henze, Andrea and Ungru, Julia and Schweigert, Florian Johannes and Raila, Jens and Vervuert, Ingrid}, title = {Determination of lipid profiles in serum of obese ponies before and after weight reduction by using multi-one-dimensional thin-layer chromatography}, series = {Research in veterinary science}, volume = {117}, journal = {Research in veterinary science}, publisher = {Elsevier}, address = {Oxford}, issn = {0034-5288}, doi = {10.1016/j.rvsc.2017.11.013}, pages = {111 -- 117}, year = {2017}, abstract = {Obesity is a key component of equine metabolic syndrome, which is highly associated with laminitis. Feed restriction and/or exercise are known to alleviate the detrimental effects of insulin resistance in obese ponies. However, little is known about changes in the serum lipid patterns due to weight reduction and its association with disease outcomes. Therefore, the lipid patterns in the serum of 14 mature ponies before and after a 14-week body weight reduction program (BWRP) were investigated by multi-one-dimensional thin-layer chromatography (MOD-TLC). Additionally, sensitivity to insulin (SI), body condition scores (BCS) and cresty neck scores (CNS) were measured. A BWRP resulted in a significant loss of body weight (P < 0.001), which was associated with beneficial decreases in BCS and CNS (both, P < 0.001). Serum lipid compositions revealed significantly increased free fatty acid (FFA), sphingomyelin (SM; both P < 0.001), total cholesterol (C) and cholesterol ester (CE) (both P < 0.01) and triacylglycerol (TG; P < 0.05) densities. Improvement of SI after the BWRP was associated with increases in neutral lipids (C, CE and TG, all P < 0.01), FFA and the phospholipid SM (both, P < 0.001). The results show that a BWRP in obese ponies was effective and associated with changes in the concentrations of neutral lipids and the phospholipid SM, indicating that SM may play a role in insulin signaling pathways and thus in the pathogenesis of insulin resistance and the progression of metabolic syndrome in obese ponies.}, language = {en} } @phdthesis{Weitkunat2017, author = {Weitkunat, Karolin}, title = {Dietary fibers and short-chain fatty acids in the development of diet-induced obesity}, school = {Universit{\"a}t Potsdam}, pages = {121}, year = {2017}, language = {en} }