Zellvitalität von Glioblastomzellen und Fibroblasten in Anwesenheit von imidazolhaltigen Stoffen

Das Glioblastom ist der häufigste maligne Hirntumor. Unter der aktuellen Standardtherapie bestehend aus möglichst kompletter Resektion, kombinierter Radiochemotherapie und einer Erhaltungstherapie mit Temozolomid bleibt die Prognose mit einer 5-Jahresüberlebensrate von 7,2% schlecht. Das natürlich vorkommende Dipeptid L-Carnosin (β-Alanyl-L-Histidin) schwächt das Wachstum von Tumorzellen ab. In der vorliegenden Arbeit sind wir der Frage nachgegangen, ob andere kleine imidazolhaltige Substanzen auch die Vitalität von Glioblastomzellen beeinflussen ohne dabei nicht-maligne Zellen zu beeinflussen und ob diesem Effekt die Bildung von Histamin zugrunde liegt. Primäre Fibroblastenkulturen und Glioblastomzellen wurden mit L-Carnosin, L-Alanyl-L-Histidin, β-Alanyl-L-Alanin, L-Histidin, Histamin, Imidazol, β-Alanin und L-Alanin für 48 Stunden behandelt. Über zellbasierte Vitalitätsassays und mikroskopische Analysen wurde die Zellvitalität unter dem Einfluss der verschiedenen Substanzen sowohl von den primären Fibroblastenkulturen als auch den Glioblastomzellen bestimmt. Zudem wurde die intrazelluläre Freisetzung von L-Histidin und die Bildung von Histamin nach Behandlung der Zellen entweder mit L-Carnosin oder mir L-Alanyl-L-Histidin mittels Hochleistungsflüssigkeitschromatographie (HPLC) bestimmt. L-Carnosin und L-Alanyl-L-Histidin hemmten das Tumorwachstums bei gleichzeitig nur geringem Effekt auf die Vitalität der primären Fibroblastenkulturen. L-Histidin, Histamin und Imidazol hingegen reduzierten die Zellvitalität beider Zelltypen. Substanzen die keinen Imidazolanteil besaßen hatten keinen Einfluss auf die Zellvitalität. In Anwesenheit von L-Alanyl-L-Histidin aber nicht von L-Carnosin kam es zu einem signifikanten Anstieg der intrazellulären L-Histidinmenge. Die Bildung von Histamin konnte weder nach Behandlung der Zellen mit L-Carnosin und L-Alanyl-L-Histidin noch mit L-Histidin nachgewiesen werden. Zusammenfassend trägt der Imidazolanteil zum antineoplastischen Effekt von L-Carnosin bei, was auch auf den Effekt von L-Alanyl-L-Histidin und L-Histidin zutrifft. Obwohl Histamin einen starken Einfluss auf die Zellvitalität ausübt, ist die Bildung von Histamin nicht für den antineoplastischen Effekt von L-Carnosin, L-Alanyl-L-Histidin und L-Histidin verantwortlich

Optimized Synthesis of Tetrafluoroterephthalic Acid: A Versatile Linking Ligand for the Construction of New Coordination Polymers and Metal-Organic Frameworks

Pure 2,3,5,6-tetrafluoroterephthalic acid (H(2)tfBDC) is obtained in high yields (95%) by reacting 1,2,4,5-tetrafluorobenzene with a surplus (>2 equiv) of n-butyllithium in tetrahydrofuran (THF) and subsequent carbonation with CO2 without any extensive purification procedure. A single crystal X-ray structure analysis of H2tfBDC (1) confirms former data obtained for a deuterated sample (P (1) over bar, Z = 1). Recrystallization from water/acetone leads to single crystals of H(2)tfBDC center dot 2H(2)O (2, P2(1)/c, Z. 2), where an extensive hydrogen bonding network is found. By reacting H2tfBDC with an aqueous ammonia solution, single crystals of (NH4)(2)tfBDC (3, C2/m, Z. 2) are obtained. 3 is thermally stable up to 250 degrees C and shows an enhanced solubility in water compared to H(2)tfBDC. Monosubstituted 2,3,5,6-tetrafluorobenzoic acid (H(2)tfBC, 4) is obtained by reacting 1,2,4,5-tetrafluorobenzene with stoichiometric amounts (1 equiv) of n-butyllithium in THF. Its crystal structure (Fdd2, Z = 16) shows dimeric units as characteristic structural feature

Feasibility, Impact on Symptoms and Mentalising Capacity

This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self- efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow- up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention- to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function

Viability of Glioblastoma Cells and Fibroblasts in the Presence of Imidazole-Containing Compounds

The naturally occurring dipeptide carnosine (-alanyl-L-histidine) specifically attenuates tumor growth. Here, we ask whether other small imidazole-containing compounds also affect the viability of tumor cells without affecting non-malignant cells and whether the formation of histamine is involved. Patient-derived fibroblasts and glioblastoma cells were treated with carnosine, L-alanyl-L-histidine (LA-LH), -alanyl-L-alanine, L-histidine, histamine, imidazole, -alanine, and L-alanine. Cell viability was assessed by cell-based assays and microscopy. The intracellular release of L-histidine and formation of histamine was investigated by high-performance liquid chromatography coupled to mass spectrometry. Carnosine and LA-LH inhibited tumor cell growth with minor effects on fibroblasts, and L-histidine, histamine, and imidazole affected viability in both cell types. Compounds without the imidazole moiety did not diminish viability. In the presence of LA-LH but not in the presence of carnosine, a significant rise in intracellular amounts of histidine was detected in all cells. The formation of histamine was not detectable in the presence of carnosine, LA-LH, or histidine. In conclusion, the imidazole moiety of carnosine contributes to its anti-neoplastic effect, which is also seen in the presence of histidine and LA-LH. Despite the fact that histamine has a strong effect on cell viability, the formation of histamine is not responsible for the effects on the cell viability of carnosine, LA-LH, and histidine

Ultrafine carbon particles down-regulate CYP1B1 expression in human monocytes

Cytochrome P450 monoxygenases play an important role in the defence against inhaled toxic compounds and in metabolizing a wide range of xenobiotics and environmental contaminants. In ambient aerosol the ultrafine particle fraction which penetrates deeply into the lungs is considered to be a major factor for adverse health effects. The cells mainly affected by inhaled particles are lung epithelial cells and cells of the monocyte/macrophage lineage. RESULTS: In this study we have analyzed the effect of a mixture of fine TiO2 and ultrafine carbon black Printex 90 particles (P90) on the expression of cytochrome P450 1B1 (CYP1B1) in human monocytes, macrophages, bronchial epithelial cells and epithelial cell lines. CYP1B1 expression is strongly down-regulated by P90 in monocytes with a maximum after P90 treatment for 3 h while fine and ultrafine TiO2 had no effect. CYP1B1 was down-regulated up to 130-fold and in addition CYP1A1 mRNA was decreased 13-fold. In vitro generated monocyte-derived macrophages (MDM), epithelial cell lines, and primary bronchial epithelial cells also showed reduced CYP1B1 mRNA levels. Benzo[a]pyrene (BaP) is inducing CYB1B1 but ultrafine P90 can still down-regulate gene expression at 0.1 muM of BaP. The P90-induced reduction of CYP1B1 was also demonstrated at the protein level using Western blot analysis. CONCLUSION: These data suggest that the P90-induced reduction of CYP gene expression may interfere with the activation and/or detoxification capabilities of inhaled toxic compounds

Vorsorge gegen den Maiszünsler im pfluglosen Anbau

Die Broschüre fasst die Ergebnisse einer Untersuchung zur wirksamen Bekämpfung von Maiszünslerlarven auf dauerhaft konservierend bestellten Ackerflächen zusammen. Der alleinige Einsatz von Pflug und Grubber zeigte keine ausreichende Wirkung, weil der Anteil intakter und für die Überwinterung der Larven geeigneter Maisstoppeln zu groß ist. Der Einsatz des Pfluges erhöhte die Erosionsgefährdung des Bodens. Lediglich die Scheibenegge zeigte als Sologerät eine hinreichende Zerkleinerungswirkung bei der flachen Einarbeitung der Erntereste. In Kombination mit dem Mulcher werden bei allen untersuchten Bodenbearbeitungsvarianten ausreichend Maisstoppeln beschädigt. Es kann empfohlen werden, Maisstoppeln mit einer Kombination aus Mulcher und Scheibenegge bzw. Grubber zu bearbeiten. So kann bei hinreichendem Erosionsschutz der Maiszünslervermehrung vorgebeugt werden. Gleichzeitig wird damit die Gefahr einer Fusarieninfektion im nachgebauten Getreide reduziert

GRB Light Curves in the Relativistic Turbulence Model

Randomly oriented relativistic emitters in a relativistically expanding shell provides an alternative to internal shocks as a mechanism for producing GRBs' variable light curves with efficient conversion of energy to radiation. In this model the relativistic outflow is broken into small emitters moving relativistically in the outflow's rest frame. Variability arises because an observer sees an emitter only when its velocity points towards him so that only a small fraction of the emitters are seen by a given observer. Models with significant relativistic random motions require converting and maintaining a large fraction of the overall energy into these motions. While it is not clear how this is achieved, we explore here, using two toy models, the constraints on parameters required to produce light curves comparable to the observations. We find that a tight relation between the size of the emitters and the bulk and random Lorentz factors is needed and that the random Lorentz factor determines the variability. While both models successfully produce the observed variability there are several inconsistencies with other properties of the light curves. Most of which, but not all, might be resolved if the central engine is active for a long time producing a number of shells, resembling to some extent the internal shocks model.Comment: Significantly revised with a discussion of additional models. Accepted for publication in APJ