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  • 1
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Sevofluran ; Sevofluranreaktionen ; Kaliumhydroxid ; Natriumhydroxid ; Kalziumhydroxid ; Bariumhydroxid ; Key words Sevoflurane ; Sevoflurane reactions ; Potassium hydroxide ; Sodium hydroxide ; Calcium hydroxide ; Barium hydroxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The various components of commercial soda lime (sodium hydroxide, potassium hydroxide, calcium hydroxide, barium hydroxide) were studied in terms of their reactivity with sevoflurane at its boiling point (59° C). A simple closed system, a reflux cooler, served as a model. Analyses were performed by GC/MS. Besides sevoflurane, we identified four compounds: A, B, C, and D. Free methanol, formaldehyde and formic acid could not be found. Presumably methanol is transferred from an intermediate formalin-semiacetal of the hexafluorisopropanol. Calcium hydroxide and barium hydroxide showed little reaction with sevoflurane, whereas larger amounts of reaction products were observed with sodium hydroxide and potassium hydroxide. The alkali hydroxides of sodalime are presumably responsible for its reaction with halogenated inhalation anaesthetics. We therefore conclude that decomposing reactions of halogenated inhalation anesthetics with dry soda lime could be prevented by using a newly developed soda lime.
    Notes: Zusammenfassung In einem einfachen geschlossenen System als Modell (Rückflußkühler) wurden die verschiedenen Komponenten von kommerziellem Atemkalk (Natriumhydroxid, Kaliumhydroxid, Kalziumhydroxid, Bariumhydroxid) auf ihr Reaktionsverhalten mit Sevofluran an dessen Siedepunkt (59° C) untersucht. Die Analysen erfolgten mittels GC/MS. Identifiziert wurden neben Sevofluran Compound A, B, C, D. Freies Methanol wurde ebenso wie Formaldehyd oder Ameisensäure nicht gefunden. Daher wird angenommen, daß eine Methanolübertragung aus einem intermediären Formaldehydsemiacetal mit Hexafluorisopropanol erfolgt. Während Kalziumhydroxid und Bariumhydroxid kaum eine Reaktion mit Sevofluran zeigen, können mit Natriumhydroxid und Kaliumhydroxid die entsprechenden Reaktionsprodukte in größerem Umfang festgestellt werden. Es wird daher gefolgert, daß die Alkalihydroxide des Atemkalks für dessen Reaktion mit halogenierten Inhalationsanästhetika verantwortlich sind. Daraus ist zu folgern, daß mittels eines neu zu konzipierenden Atemkalks die Zerfallsreaktionen von halogenierten Inhalationsanästhetika an trockenem Atemkalk verhindert werden könnten.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Sevofluran ; Inhalationsanästhetikum ; Compound ; A, Lithiumhydroxid ; Kohlendioxidabsorption ; Atemkalk ; Key words Sevoflurane ; Inhalational anaesthetics ; Carbon dioxide absorption ; Compound A ; Lithiumhydroxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Aim of the study was the clinical investigation of sevoflurane degradation when using water-free lithiumhydroxide versus moist Drägersorb® 800 for carbon dioxide absorption. Methods: Concentrations of Compound A in the inspiratory gas mix and serum fluoride levels were measured in two groups of 8 patients each. Results: When water-free lithiumhydroxide was used for carbon dioxide absorption, concentration of Compound A in the inspiratory gas mix was ca. 1 ppm (near minimal level of detection) as compared to ca. 20 ppm for moist Drägersorb® 800. The concentration of fluoride increased during sevoflurane anesthesia (15,0±4,8 μmol/l with lithiumhydroxide versus 21,9±4,0 μmol/l with Drägersorb® 800 after 60 mins). Conclusions: When lithiumhydroxide is used, there is only minimal formation of compound A from sevoflurane degradation. Since serum fluoride levels increased in both patient groups, we conclude that this is caused mainly by metabolism of sevoflurane. Capacity of lithiumhydroxide for carbon dioxide absorption is similar to that of Drägersorb® 800. Therefore, the use of lithiumhydroxide increases patient safety.
    Notes: Zusammenfassung Fragestellung: In einer klinischen Studie wurde die Degradation von Sevofluran bei Verwendung von wasserfreiem Lithiumhydroxid zur Kohlendioxidabsorption im Vergleich zu feuchtem Drägersorb® 800 untersucht. Methodik: Bei jeweils 8 Patienten wurde die Konzentration von Compound A im Inspirationsgas und die Fluoridkonzentration im Serum der Patienten gemessen. Ergebnisse: Bei Einsatz von wasserfreiem Lithiumhydroxid zur Kohlendioxidabsorption blieb die Compound A Konzentration im Inspirationsgas im Bereich der Nachweisgrenze (um 1 ppm). Demgegenüber wurden bei Verwendung von feuchtem Drägersorb® 800 in Übereinstimmung mit der Literatur Werte um 20 ppm gemessen. Die Fluoridkonzentration im Serum stieg zu Beginn der Narkose auch bei Einsatz von Lithiumhydroxid an (15,0±4,8 μmol/l gegenüber 21,9±4,0 μmol/l nach 60 min). Schlußfolgerungen: In den Untersuchungen wurde nachgewiesen, daß bei Verwendung von Lithiumhydroxid Compound A nur in Spuren aus Sevofluran gebildet wird. Aus dem Anstieg der Fluoridkonzentration im Serum bei beiden Patientengruppen kann gefolgert werden, daß dieses vorwiegend aus dem Metabolismus des Sevofluran stammt. Die Kapazität des Lithiumhydroxid zur Kohlendioxidabsorption ist der des Drägersorb® 800 vergleichbar. Damit kann durch Verwendung von Lithiumhydroxid die Narkosesicherheit erhöht werden.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2018-06-16
    Description: Purpose: Successful immunotherapies for IDH mut gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous T-cell responses using an unbiased proteomic approach. Experimental Design: Protein fractionations of tissue lysates from IDH mut gliomas ( n = 4) were performed. Fractions were tested by IFN ELISpot assay for recognition through patients' T cells. Proteins of immunogenic fractions were identified by mass spectrometry and validated by in silico -predicted synthetic long peptides in patients of origin, additional IDH mut glioma patients ( n = 16), and healthy donors ( n = 13). mRNA and protein expression of immunogenic antigens was analyzed in tumor tissues and IDH mut glioma stem-like cells (GSC). HLA-A*02–restricted T-cell epitopes were functionally determined by short peptides and numbers of antigen-specific T cells by HLA-peptide tetramer analysis. Results: A total of 2,897 proteins were identified in immunogenic tumor fractions. Based on a thorough filter process, 79 proteins were selected as potential T-cell antigens. Twenty-six of these were recognized by the patients’ T cells, and five of them (CRKII, CFL1, CNTN1, NME2, and TKT) in up to 56% unrelated IDH mut glioma patients. Most immunogenic tumor-associated antigens (TAA) were expressed in IDH mut gliomas and GSCs, while being almost absent in normal brain tissues. Finally, we identified HLA-A*02–restricted epitopes for CRKII, NME2, and TKT that were recognized by up to 2.82% of antigen-specific peripheral cytotoxic T cells in IDH mut glioma patients. Conclusions: By analyzing the repertoire of T-cell target antigens in IDH mut glioma patients, we identified five novel immunogenic TAAs and confirmed their expression on IDH mut tumors and GSCs. Clin Cancer Res; 24(12); 2951–62. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 4
    Publication Date: 2018-05-02
    Description: Coimmunoprecipitation (co-IP) is one of the most frequently used techniques to study protein-protein (PPIs) or protein-nucleic acid interactions (PNIs). However, the presence of coprecipitated contaminants is a well-recognized issue associated with single-step co-IPs. To overcome this limitation, we developed the two-step co-IP (TIP) strategy that enables sequential coimmunoprecipitations of endogenous protein complexes. TIP can be performed with a broad range of mono- and polyclonal antibodies targeting a single protein or different components of a given complex. TIP results in a highly selective enrichment of protein complexes and thus outperforms single-step co-IPs for downstream applications such as mass spectrometry for the identification of PPIs and quantitative PCR for the analysis of PNIs. We benchmarked TIP for the identification of CD95/FAS-interacting proteins in primary human CD4 + T cells, which recapitulated all major known interactors, but also enabled the proteomics discovery of PPM1G and IPO7 as new interaction partners. For its feasibility and high performance, we propose TIP as an advanced tool for the isolation of highly purified protein-protein and protein-nucleic acid complexes under native expression conditions.
    Print ISSN: 1535-9476
    Electronic ISSN: 1535-9484
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2011-04-02
    Description: Members of the tumour necrosis factor (TNF) receptor superfamily have important functions in immunity and inflammation. Recently linear ubiquitin chains assembled by a complex containing HOIL-1 and HOIP (also known as RBCK1 and RNF31, respectively) were implicated in TNF signalling, yet their relevance in vivo remained uncertain. Here we identify SHARPIN as a third component of the linear ubiquitin chain assembly complex, recruited to the CD40 and TNF receptor signalling complexes together with its other constituents, HOIL-1 and HOIP. Mass spectrometry of TNF signalling complexes revealed RIP1 (also known as RIPK1) and NEMO (also known as IKKgamma or IKBKG) to be linearly ubiquitinated. Mutation of the Sharpin gene (Sharpin(cpdm/cpdm)) causes chronic proliferative dermatitis (cpdm) characterized by inflammatory skin lesions and defective lymphoid organogenesis. Gene induction by TNF, CD40 ligand and interleukin-1beta was attenuated in cpdm-derived cells which were rendered sensitive to TNF-induced death. Importantly, Tnf gene deficiency prevented skin lesions in cpdm mice. We conclude that by enabling linear ubiquitination in the TNF receptor signalling complex, SHARPIN interferes with TNF-induced cell death and, thereby, prevents inflammation. Our results provide evidence for the relevance of linear ubiquitination in vivo in preventing inflammation and regulating immune signalling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerlach, Bjorn -- Cordier, Stefanie M -- Schmukle, Anna C -- Emmerich, Christoph H -- Rieser, Eva -- Haas, Tobias L -- Webb, Andrew I -- Rickard, James A -- Anderton, Holly -- Wong, Wendy W-L -- Nachbur, Ueli -- Gangoda, Lahiru -- Warnken, Uwe -- Purcell, Anthony W -- Silke, John -- Walczak, Henning -- 10950/Cancer Research UK/United Kingdom -- England -- Nature. 2011 Mar 31;471(7340):591-6. doi: 10.1038/nature09816.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tumour Immunology Unit, Department of Medicine, Imperial College London, W12 0NN London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21455173" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CD40 Ligand/metabolism ; Carrier Proteins/chemistry/metabolism ; Cell Line ; Humans ; I-kappa B Kinase/metabolism ; Immunity/*immunology ; Inflammation/*metabolism/pathology/prevention & control ; Interleukin-1beta/metabolism ; Mice ; Multiprotein Complexes/chemistry/metabolism ; NF-kappa B/metabolism ; Nerve Tissue Proteins/chemistry/genetics/metabolism ; Phenotype ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism ; Receptors, Tumor Necrosis Factor/deficiency/genetics/metabolism ; *Signal Transduction ; Skin/cytology/immunology/metabolism/pathology ; Tumor Necrosis Factor-alpha/deficiency/genetics ; Ubiquitin/chemistry/metabolism ; Ubiquitin-Protein Ligase Complexes/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/metabolism ; *Ubiquitination
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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