Neugestaltung des Spielplatzes Geuernrain in Esslingen-Pliensauvorstadt : Planung mit Bürgerbeteiligung

Die Aufgabe für diese Diplomarbeit war die Neugestaltung des Spielplatzes Geuernrain in Esslingen-Pliensauvorstadt. Ein Wunsch der Stadt war dabei die Ausrichtung des Ortes auf ältere Kinder und Jugendliche zwischen 11 und 16 Jahren. Entstehen sollte ein Abenteuer- und Naturspielplatz. Nach gründlicher Analyse der Gegebenheiten kamen wir zu dem Schluss, dass der Geuernrain mehr Potential bietet. Aufgrund seiner stadtnahen und doch grünen Lage stellt er sowohl für Kinder und Jugendliche, als auch für Erwachsene ein attraktives Ziel dar. Wir kamen zu dem Ergebnis, dass der Geuernrain ein Ort für alle werden sollte.In einem übergeordneten Konzept stellten wir die großmaßstäblichen Ziele dar, die aus der Bestandsanalyse unter Berücksichtigung der Wünsche entwickelt wurden. Anschließend brachten Kinder der Pliensauvorstadt in der Zukunftswerkstatt ihre Ideen für die Planung ein. Auf dieser Grundlage entwickelten wir vier Vorentwürfe. Diese präsentierten wir auf einem Fest in der Pliensauvorstadt, wo die Bürger über ihren Favoriten abstimmen konnten. Wir überarbeiteten den Plan, der am meisten gewünscht wurde und entwickelten ihn zum Entwurf weiter. Als letzte Stufe der Bürgerbeteiligung ist es geplant, die Ergebnisse der Diplomarbeit in der Esslinger Zeitung vorzustellen

Concept for the Evaluation of Carcinogenic Substances in Population-Based Human Biomonitoring

The Human Biomonitoring (HBM) Commission at the German Environment Agency holds the opinion that for environmental carcinogens for which no exposure levels can be assumed and are harmless to health, health-based guidance values corresponding to the classical definition of the HBM-I or HBM-II value cannot be established. Therefore, only reference values have been derived so far for genotoxic carcinogens from exposure data of the general population or subpopulations. The concept presented here opens up the possibility of performing health risk assessments of carcinogenic substances in human biomonitoring, and thus goes decisively beyond the purely descriptive statistical reference value concept. Using the presented method, quantitative dose descriptors of internal exposure can be derived from those of external exposure, provided that sufficient toxicokinetic information is available. Dose descriptors of internal exposure then allow the simple estimate of additional lifetime cancer risks for measured biomarker concentrations or, conversely, of equivalent concentrations for selected risks, such as those considered as tolerable for the general population. HBM data of chronic exposures to genotoxic carcinogens can thus be used to assess the additional lifetime cancer risk referring to the general population and to justify and prioritize risk management measures

Activation of 3-nitrobenzanthrone and its metabolites by human acetyltransferases, sulfotransferases and cytochrome P450 expressed in Chinese hamster V79 cells

"Activation of 3-nitrobenzanthrone and its metabolites by human acetyltransferases sulfotransferases and cytochrome P450 expressed in chinese hamster V79 cells. 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and ambient air pollution. 3-Aminobenzanthrone (3-ABA) 3-acetylaminobenzanthrone (3-Ac-ABA) and N-acetyl-N-hydroxy-3-aminobenzanthrone (N-Ac-N-OH-ABA) have been identified as 3-NBA metabolites. Recently we found that 3-NBA and its metabolites (3-ABA 3-Ac-ABA and N-Ac-N-OH-ABA) form the same DNA adducts in vivo in rats. In order to investigate whether human cytochrome P450 (CYP) enzymes (i.e. CYP1A2) human NO-acetyltransferases (NATs) and sulfotransferases (SULTs) contribute to the metabolic activation of 3-NBA and its metabolites we developed a panel of Chinese hamster V79MZ-h1A2 derived cell lines expressing human CYP1A2 in conjunction with human NAT1 NAT2 SULT1A1 or SULT1A2 respectively. Cells were treated with 0.01 0.1 or 1 M 3-NBA or its metabolites (3-ABA 3-Ac-ABA and N-Ac-N-OH-ABA). Using both enrichment versions of the 32P-postlabeling assay nuclease P1 digestion and butanol extraction essentially 4 major and 2 minor DNA adducts were detected in the appropriate cell lines with all 4 compounds. The major ones were identical to those detected in rat tissue; the adducts lack an N-acetyl group. Human CYP1A2 was required for the metabolic activation of 3-ABA and 3-Ac-ABA (probably via N-oxidation) and enhanced the activity of 3-NBA (probably via nitroreduction). The lack of acetylated adducts suggests N-deacetylation of 3-Ac-ABA and N-Ac-N-OH-ABA. Thus N-hydroxy-3-aminobenzanthrone (N-OH-ABA) appears to be a common intermediate for the formation of the electrophilic arylnitrenium ions capable of reacting with DNA. Human NAT1 and NAT2 as well as human SULT1A1 and SULT1A2 strongly contributed to the high genotoxicity of 3-NBA and its metabolites. Moreover NO-acetyltransfer reactions catalyzed by human NATs leading to the corresponding N-acetoxyester may be important in the bioactivation of N-Ac-N-OH-ABA. As human exposure to 3-NBA is likely to occur primarily via the respiratory tract expression of CYPs NATs and SULTs in respiratory tissues may contribute significantly and specifically to the metabolic activation of 3-NBA and its metabolites. Consequently polymorphisms in these genes could be important determinants of lung cancer risk from 3-NBA. © 2003 Wiley-Liss Inc.

Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial

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