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91.
92.
Heidi Hrabetz Horst Thiermann Norbert Felgenhauer Thomas Zilker Bernhard Haller Jörg Nährig Bernd Saugel Florian Eyer 《Chemico-biological interactions》2013
Organophosphate (OP) poisoning is still associated with high morbidity and mortality rates, both in resource-poor settings and in well-developed countries. Despite numerous publications dealing with this particular poison, detailed clinical data on more severe overdoses with these agents are relatively sparsely reported. A retrospective study was consequently conducted on 33 patients with OP poisoning admitted to our intensive care unit (ICU) to provide additional data on clinical features. We included moderate to severe poisonings between 2000 and 2012 who required admission to ICU. 相似文献
93.
Bernat Elvira Sabina Honisch Ahmad Almilaji Tatsiana PakladokGuilai Liu Ekaterina ShumilinaIoana Alesutan Wenting YangCarlos Munoz Florian Lang 《生物化学与生物物理学报:生物膜》2013
The Na+-coupled glucose transporter SGLT1 (SLC5A1) accomplishes concentrative cellular glucose uptake even at low extracellular glucose concentrations. The carrier is expressed in renal proximal tubules, small intestine and a variety of nonpolarized cells including several tumor cells. The present study explored whether SGLT1 activity is regulated by caveolin-1, which is known to regulate the insertion of several ion channels and carriers in the cell membrane. To this end, SGLT1 was expressed in Xenopus oocytes with or without additional expression of caveolin-1 and electrogenic glucose transport determined by dual electrode voltage clamp experiments. In SGLT1-expressing oocytes, but not in oocytes injected with water or caveolin-1 alone, the addition of glucose to the extracellular bath generated an inward current (Ig), which was increased following coexpression of caveolin-1. Kinetic analysis revealed that caveolin-1 increased maximal Ig without significantly modifying the glucose concentration required to trigger half maximal Ig (KM). According to chemiluminescence and confocal microscopy, caveolin-1 increased SGLT1 protein abundance in the cell membrane. Inhibition of SGLT1 insertion by brefeldin A (5 μM) resulted in a decline of Ig, which was similar in the absence and presence of caveolin-1. In conclusion, caveolin-1 up-regulates SGLT1 activity by increasing carrier protein abundance in the cell membrane, an effect presumably due to stimulation of carrier protein insertion into the cell membrane. 相似文献
94.
Tsutomu Akama Charlotte Virtucio Chen Dong Richard Kimura Yong-Kang Zhang James A. Nieman Rashmi Sharma Xiaosong Lu Marcelo Sales Rajeshwar Singh Anne Wu Xiao-Qing Fan Liang Liu Jacob J. Plattner Kurt Jarnagin Yvonne R. Freund 《Bioorganic & medicinal chemistry letters》2013,23(6):1680-1683
A series of novel 6-(aminomethylphenoxy)benzoxaborole analogs was synthesized for the investigation of the structure–activity relationship of the inhibition of TNF-alpha, IL-1beta, and IL-6, from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compounds 9d and 9e showed potent activity against all three cytokines with IC50 values between 33 and 83 nM. Chloro substituted analog 9e (AN3485) is considered to be a promising lead for novel anti-inflammatory agent with a favorable pharmacokinetic profile. 相似文献
95.
Tsutomu Akama Chen Dong Charlotte Virtucio Yvonne R. Freund Daitao Chen Matthew D. Orr Robert T. Jacobs Yong-Kang Zhang Vincent Hernandez Yang Liu Anne Wu Wei Bu Liang Liu Kurt Jarnagin Jacob J. Plattner 《Bioorganic & medicinal chemistry letters》2013,23(21):5870-5873
Structure–activity relationships of 6-(benzoylamino)benzoxaborole analogs were investigated for the inhibition of TNF-α, IL-1β, and IL-6 from lipopolysaccharide stimulated peripheral blood mononuclear cells. Compound 1q showed potent activity against all three cytokines with IC50 values between 0.19 and 0.50 μM, inhibited LPS-induced TNF-α and IL-6 elevation in mice and improved collagen-induced arthritis in mice. Compound 1q (AN4161) is considered to be a promising lead for novel anti-inflammatory agent with an excellent pharmacokinetic profile. 相似文献
96.
Ingo V. Hartung Marion Hitchcock Florian Pühler Roland Neuhaus Arne Scholz Stefanie Hammer Kirstin Petersen Gerhard Siemeister Dominic Brittain Roman C. Hillig 《Bioorganic & medicinal chemistry letters》2013,23(8):2384-2390
Using PD325901 as a starting point for identifying novel allosteric MEK inhibitors with high cell potency and long-lasting target inhibition in vivo, truncation of its hydroxamic ester headgroup was combined with incorporation of alkyl and aryl ethers at the neighboring ring position. Whereas alkoxy side chains did not yield sufficient levels of cell potency, specifically substituted aryloxy groups allowed for high enzymatic and cellular potencies. Sulfamide 28 was identified as a highly potent MEK inhibitor with nanomolar cell potency against B-RAF (V600E) as well as Ras-mutated cell lines, high metabolic stability and resulting long half-lives. It was efficacious against B-RAF as well as K-Ras driven xenograft models and showed—despite being orally bioavailable and not a P-glycoprotein substrate—much lower brain/plasma exposure ratios than PD325901. 相似文献
97.
Florian Hubrich Silja Mordhorst Jennifer N. Andexer 《Bioorganic & medicinal chemistry letters》2013,23(5):1477-1481
Chorismatases and isochorismatases catalyse the hydrolysis of chorismate or isochorismate leading to unsaturated cyclohexenoic acid derivatives. Based on simplification of the physiological substrates, two cinnamic acid-derived compounds, differing in the saturation of the side chain, were developed. In contrast to earlier inhibitor studies, the compounds described here do not have an ether bond and therefore can be synthesised very easily in one or two steps without the need for protective groups. Both substances demonstrate inhibition of the isochorismatase EntB from Escherichia coli and the chorismatases FkbO and Hyg5 from Streptomyces. For chorismatases, the unsaturated compound shows IC50 values in the millimolar range, while the saturated compound is the better inhibitor with IC50 values in the micromolar/low millimolar range; for the isochorismatase tested both compounds inhibit in the micromolar range. Further, an analysis of the apparent Km values for FkbO and EntB was performed, showing that both inhibitors act in a competitive manner. Due to the ease of modifying these new inhibitors they are a suitable starting point for exploring further functionalised derivatives. 相似文献
98.
99.
Katarina Stingl Karl Ulrich Bartz-Schmidt Dorothea Besch Angelika Braun Anna Bruckmann Florian Gekeler Udo Greppmaier Stephanie Hipp Gernot H?rtd?rfer Christoph Kernstock Assen Koitschev Akos Kusnyerik Helmut Sachs Andreas Schatz Krunoslav T. Stingl Tobias Peters Barbara Wilhelm Eberhart Zrenner 《Proceedings. Biological sciences / The Royal Society》2013,280(1757)
This study aims at substituting the essential functions of photoreceptors in patients who are blind owing to untreatable forms of hereditary retinal degenerations. A microelectronic neuroprosthetic device, powered via transdermal inductive transmission, carrying 1500 independent microphotodiode-amplifier-electrode elements on a 9 mm2 chip, was subretinally implanted in nine blind patients. Light perception (8/9), light localization (7/9), motion detection (5/9, angular speed up to 35 deg s−1), grating acuity measurement (6/9, up to 3.3 cycles per degree) and visual acuity measurement with Landolt C-rings (2/9) up to Snellen visual acuity of 20/546 (corresponding to decimal 0.037 or corresponding to 1.43 logMAR (minimum angle of resolution)) were restored via the subretinal implant. Additionally, the identification, localization and discrimination of objects improved significantly (n = 8; p < 0.05 for each subtest) in repeated tests over a nine-month period. Three subjects were able to read letters spontaneously and one subject was able to read letters after training in an alternative-force choice test. Five subjects reported implant-mediated visual perceptions in daily life within a field of 15° of visual angle. Control tests were performed each time with the implant''s power source switched off. These data show that subretinal implants can restore visual functions that are useful for daily life. 相似文献
100.
Florian Capito Romas Skudas Bernd Stanislawski Harald Kolmar 《Biotechnology progress》2013,29(1):265-274
Production of recombinant proteins, e.g. antibodies, requires constant real‐time monitoring to optimize yield and quality attributes and to respond to changing production conditions, such as host cell protein (HCP) titers. To date, this monitoring of mammalian cell culture‐based processes is done using laborious and time consuming enzyme‐linked immunosorbent assays (ELISA), two‐dimensional sodium dodecylsulphate polyacrylamide gel electrophoresis, and chromatography‐based systems. Measurements are usually performed off‐line, requiring regular sample withdrawal associated with increased contamination risk. As information is obtained retrospectively, the reaction time to adapt to process changes is too long, leading to lower yield and higher costs. To address the resulting demand for continuous online‐monitoring systems, we present a feasibility study using attenuated total reflection spectroscopy (ATR) to monitor mAb and HCP levels of NS0 cell culture in situ, taking matrix effects into account. Fifty‐six NS0 cell culture samples were treated with polyelectrolytes for semi‐selective protein precipitation. Additionally, part of the samples was subjected to filtration prior to analysis, to change the background matrix and evaluate effects on chemometric quantification models. General models to quantify HCP and mAb in both filtered and unfiltered matrix showed lower prediction accuracy compared to models designed for a specific matrix. HCP quantification in the range of 2,000–55,000 ng mL?1 using specific models was accurate for most samples, with results within the accepted limit of an ELISA assay. In contrast, mAb prediction was less accurate, predicting mAb in the range of 0.2–1.7 g L?1. As some samples deviated substantially from reference values, further investigations elucidating the suitability of ATR for monitoring are required. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2013 相似文献