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61.
Bernhard Wernly Michael Lichtenauer Marcus Franz Bjoern Kabisch Johanna Muessig Maryna Masyuk Malte Kelm Uta C. Hoppe Christian Jung 《International journal of molecular sciences》2016,17(9)
Hyperglycemia is a common condition in critically ill patients admitted to an intensive care unit (ICU). These patients represent an inhomogeneous collective and hyperglycemia might need different evaluation depending on the underlying disorder. To elucidate this, we investigated and compared associations of severe hyperglycemia (>200 mg/dL) and mortality in patients admitted to an ICU for acute myocardial infarction (AMI) or sepsis as the two most frequent admission diagnoses. From 2006 to 2009, 2551 patients 69 (58–77) years; 1544 male; 337 patients suffering from type 2 diabetes (T2DM)) who were admitted because of either AMI or sepsis to an ICU in a tertiary care hospital were investigated retrospectively. Follow-up of patients was performed between May 2013 and November 2013. In a Cox regression analysis, maximum glucose concentration at the day of admission was associated with mortality in the overall cohort (HR = 1.006, 95% CI: 1.004–1.009; p < 0.001) and in patients suffering from myocardial infarction (HR = 1.101, 95% CI: 1.075–1.127; p < 0.001) but only in trend in patients admitted to an ICU for sepsis (HR = 1.030, 95% CI: 0.998–1.062; p = 0.07). Severe hyperglycemia was associated with adverse intra-ICU mortality in the overall cohort (23% vs. 13%; p < 0.001) and patients admitted for AMI (15% vs. 5%; p < 0.001) but not for septic patients (39% vs. 40%; p = 0.48). A medical history of type 2 diabetes (n = 337; 13%) was not associated with increased intra-ICU mortality (15% vs. 15%; p = 0.93) but in patients with severe hyperglycemia and/or a known medical history of type 2 diabetes considered in combination, an increased mortality in AMI patients (intra-ICU 5% vs. 13%; p < 0.001) but not in septic patients (intra-ICU 38% vs. 41%; p = 0.53) could be evidenced. The presence of hyperglycemia in critically ill patients has differential impact within the different etiological groups. Hyperglycemia in AMI patients might identify a sicker patient collective suffering from pre-diabetes or undiagnosed diabetes with its’ known adverse consequences, especially in the long-term. Hyperglycemia in sepsis might be considered as adaptive survival mechanism to hypo-perfusion and consecutive lack of glucose in peripheral cells. AMI patients with hyperglycemic derailment during an ICU-stay should be closely followed-up and extensively screened for diabetes to improve patients’ outcome. 相似文献
62.
Venkat N. Vangaveti Venkatesh M. Shashidhar Catherine Rush Usman H. Malabu Roy R. Rasalam Fiona Collier Bernhard T. Baune Richard L. Kennedy 《Lipids》2014,49(12):1181-1192
Macrophage apoptosis, a key process in atherogenesis, is regulated by oxidation products, including hydroxyoctadecadienoic acids (HODEs). These stable oxidation products of linoleic acid (LA) are abundant in atherosclerotic plaque and activate PPARγ and GPR132. We investigated the mechanisms through which HODEs regulate apoptosis. The effect of HODEs on THP‐1 monocytes and adherent THP‐1 cells were compared with other C18 fatty acids, LA and α‐linolenic acid (ALA). The number of cells was reduced within 24 hours following treatment with 9‐HODE (p < 0.01, 30 μM) and 13 HODE (p < 0.01, 30 μM), and the equivalent cell viability was also decreased (p < 0.001). Both 9‐HODE and 13‐HODE (but not LA or ALA) markedly increased caspase‐3/7 activity (p < 0.001) in both monocytes and adherent THP‐1 cells, with 9‐HODE the more potent. In addition, 9‐HODE and 13‐HODE both increased Annexin‐V labelling of cells (p < 0.001). There was no effect of LA, ALA, or the PPARγ agonist rosiglitazone (1μM), but the effect of HODEs was replicated with apoptosis‐inducer camptothecin (10μM). Only 9‐HODE increased DNA fragmentation. The pro‐apoptotic effect of HODEs was blocked by the caspase inhibitor DEVD‐CHO. The PPARγ antagonist T0070907 further increased apoptosis, suggestive of the PPARγ‐regulated apoptotic effects induced by 9‐HODE. The use of siRNA for GPR132 showed no evidence that the effect of HODEs was mediated through this receptor. 9‐HODE and 13‐HODE are potent—and specific—regulators of apoptosis in THP‐1 cells. Their action is PPARγ‐dependent and independent of GPR132. Further studies to identify the signalling pathways through which HODEs increase apoptosis in macrophages may reveal novel therapeutic targets for atherosclerosis. 相似文献
63.
Two organosilicone-modified polyurethanes are investigated as potential materials for the conservation and consolidation of natural stones. The materials are low molecular weight oligomers at the application stage and react with the humidity of the air to give polymers, forming continuous microlayers. The two differ in the length of the organosilicone chain, resulting in pronounced differences in their physical state: one forms a brittle glassy material (Tg ≈ 70°C). and the other, a soft rubbery material (Tg ≈ −100°C). The rate of the polymerization of the prepolymers was investigated at different conditions, showing a strong dependence on the presence of a catalyst and air humidity. Both these favorable conditions exist probably in the natural stone pores, enhancing the formation of the protective hydrophobic internal microlayer. © 1996 John Wiley & Sons, Inc. 相似文献
64.
Headspace solid-phase microextraction (HS-SPME) combined with gas chromatography (GC) was used for isolating and analysing pyrazines formed in a model system. This system consisted of an aqueous mixture of glucose, glycine and sodium hydroxide. Pyrazine formation was accelerated by heating in a microwave oven. Results were compared with our earlier ones using conventional techniques for isolation of pyrazines. HS-SPME-GC showed several advantages over traditional methods. The method is rapid, sensitive, easy to use and reproducible. Headspace and liquid of the model reaction were extracted and the results obtained using headspace sampling showed good agreement with the methylene chloride extraction method. In all cases, coefficients of variation of 5% or lower were obtained when the SPME extraction time was consistent. 相似文献
65.
Synthesis and Reactions of Chiral Dithiocarbamates Derived from (R)-(−)- or (S)-(+)-2- The synthesis, diastereoselective alkylation reactions, dithiocarboxylation, and aldol condensation of several substituted methyl (R1 CH2) (S)-2-(methoxymethyl)-pyrrolidine-1-dithiocarboxylates (S)- 2 and of the corresponding (R)-derivatives (R)- 2 are described. The new enantiomeric dithiocarbamates (S) -2a – e , and (R) -2a – d are obtained by reaction of (S)-(+)-[(S) -1 ] or (R)-(−)-2-(methoxymethyl)-pyrrolidine [(R) -1 ], respectively, with carbon disulfide in dry methanol/anhydrous sodium acetate and the appropriate alkylating agent. The cyclic ketene dithioacetals (S) -3 and (R) -3 are formed by dithiocarboxylation procedure of (S) -2a and (R) -2a whereas (S) -6 and (R) -6 are obtained by aldol reaction with isobutyraldehyde. (S)- 2c , d and (R) -2c , d react in a diastereoselective manner after deprotonation with n-BuLi or LiTMP/LiBr at −78°C in THF with alkyl halides to the enantiomeric compounds 4a /ent -4a, 4b /ent -4b and 5 /ent -5 , respectively. 相似文献
66.
Dr. Lukas Kröger Dr. Constantin G. Daniliuc Deeba Ensan Sebastian Borgert Dr. Christian Nienberg Miriam Lauwers Dr. Michaela Steinkrüger Prof. Joachim Jose Dr. Markus Pietsch Prof. Bernhard Wünsch 《ChemMedChem》2020,15(10):871-881
The serine/threonine kinase CK2 modulates the activity of more than 300 proteins and thus plays a crucial role in various physiological and pathophysiological processes including neurodegenerative disorders of the central nervous system and cancer. The enzymatic activity of CK2 is controlled by the equilibrium between the heterotetrameric holoenzyme CK2α2β2 and its monomeric subunits CK2α and CK2β. A series of analogues of W16 ((3aR,4S,10S,10aS)-4-{[(S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-10-(3,4,5-trimethoxyphenyl)-4,5,10,10a-tetrahydrofuro[3,4-b]carbazole-1,3(3aH)-dione ((+)- 3 a )) was prepared in an one-pot, three-component Levy reaction. The stereochemistry of the tetracyclic compounds was analyzed. Additionally, the chemically labile anhydride structure of the furocarbazoles 3 was replaced by a more stable imide ( 9 ) and N-methylimide ( 10 ) substructure. The enantiomer (−)- 3 a (Ki=4.9 μM) of the lead compound (+)- 3 a (Ki=31 μM) showed a more than sixfold increased inhibition of the CK2α/CK2β interaction (protein-protein interaction inhibition, PPII) in a microscale thermophoresis (MST) assay. However, (−)- 3 a did not show an increased enzyme inhibition of the CK2α2β2 holoenzyme, the CK2α subunit or the mutated CK2α′ C336S subunit in the capillary electrophoresis assay. In the pyrrolocarbazole series, the imide (−)- 9 a (Ki=3.6 μM) and the N-methylimide (+)- 10 a (Ki=2.8 μM) represent the most promising inhibitors of the CK2α/CK2β interaction. However, neither compound could inhibit enzymatic activity. Unexpectedly, the racemic tetracyclic pyrrolocarbazole (±)- 12 , with a carboxy moiety in the 4-position, displays the highest CK2α/CK2β interaction inhibition (Ki=1.8 μM) of this series of compounds. 相似文献
67.
Yordanka Gluhcheva Irena Pashkunova-Martic Martin Schaier Ivelin Vladov Silviya Stoykova Emilia Petrova Ekaterina Pavlova Peter Dorkov Thomas H. Helbich Bernhard Keppler Juliana Ivanova 《International journal of molecular sciences》2022,23(8)
Lead (Pb) exposure induces severe nephrotoxic effects in humans and animals. Herein, we compare the effects of two chelating agents, salinomycin and deferiprone, on Pb-induced renal alterations in mice and in the homeostasis of essential elements. Adult male mice (Institute of Cancer Research (ICR)) were randomized into four groups: control (Ctrl)—untreated mice administered distilled water for 28 days; Pb-exposed group (Pb)—mice administered orally an average daily dose of 80 mg/kg body weight (BW) lead (II) nitrate (Pb(NO3)2) during the first two weeks of the experimental protocol followed by the administration of distilled water for another two weeks; salinomycin-treated (Pb + Sal) group—Pb-exposed mice, administered an average daily dose of 16 mg/kg BW salinomycin for two weeks; deferiprone-treated (Pb + Def) group—Pb-exposed mice, administered an average daily dose of 20 mg/kg BW deferiprone for 14 days. The exposure of mice to Pb induced significant accumulation of the toxic metal in the kidneys and elicited inflammation with leukocyte infiltrations near the glomerulus. Biochemical analysis of the sera revealed that Pb significantly altered the renal function markers. Pb-induced renal toxicity was accompanied by a significant decrease in the endogenous renal concentrations of phosphorous (P), calcium (Ca), copper (Cu) and selenium (Se). In contrast to deferiprone, salinomycin significantly improved renal morphology in Pb-treated mice and decreased the Pb content by 13.62% compared to the Pb-exposed group. There was also a mild decrease in the renal endogenous concentration of magnesium (Mg) and elevation of the renal concentration of iron (Fe) in the salinomycin-treated group compared to controls. Overall, the results demonstrated that salinomycin is a more effective chelating agent for the treatment of Pb-induced alterations in renal morphology compared to deferiprone. 相似文献
68.
Stephan W. Reinhold Thomas Scherl Benjamin Stölcker Tobias Bergler Ute Hoffmann Christian Weingart Miriam C. Banas Dmitrij Kollins Martin C. Kammerl Bernd Krüger Bernhard Kaess Bernhard K. Krämer Bernhard Banas 《Lipids》2013,48(2):167-175
Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro- and anti-inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12-HETE and 15-HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12- and 15-HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12- and 15-HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection. 相似文献
69.
David Bernhard Thomas Kadyk Ulrike Krewer Sebastian Kirsch 《International Journal of Hydrogen Energy》2021,46(26):13791-13805
In this work, proton exchange membrane fuel cell cathodes are degraded with accelerated-stress-tests.These PtCo containing cathodes are analyzed at begin-of-life and end-of-test with a dedicated diagnostic procedure. For every individual load point, the oxygen transport resistance and voltage losses due to the formation of platinum oxides were obtained in addition to commonly measured electrochemical surface area, high frequency resistance, as well as cathode ionomer resistance. These data were used to break down the voltage losses into six different contributors. With this break down, performance gains and performance losses were determined at end-of-test. At low current densities, it was found that voltage losses due to degradation are dominated by the loss of specific activity and catalyst surface area - in line with the state-of-the-art knowledge. But by quantifying the losses from platinum oxide formation explicitly, we show that end-of-test an unassigned voltage loss is not only present at highest current densities, but already at low current density. More precisely, the unassigned voltage loss shows a linear increase with decreasing half cell voltage and is independent from the chosen accelerated stress test. As this unassigned loss depends on half cell voltage, it might arise from ionomer adsorption. 相似文献
70.
Multimedia Tools and Applications - Ubiquitous and networked sensors impose a huge challenge for privacy protection which has become an emerging problem of modern society. Protecting the privacy of... 相似文献