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Untersuchungen zum Einfluss eines erhöhten Omega-3 FettsÀure Gehaltes auf das Lipidmediatorenprofil und zum anti-inflammatorischen Potential der murinen 15-Lipoxygenase, 17-HydroxydocosapentaensÀure und 10,17-DihydroxydocosapentaensÀure
Long-chain polyunsaturated omega-3 (n-3 PUFA) and omega-6 fatty acids are precursors of highly potent lipid mediators and metabolites, which are synthesized via cyclooxygenases, lipoxygenases (LOX), cytochrome P450 (CYP-450) or via autooxidation processes, and their synthesis can be modulated. The lipid mediator profile, especially of monohydroxy lipid metabolites hydroxyeicosatetraenoic acids, hydroxyeicosapentaenoic acids (HEPE) and hydroxydocosahexaenoic acids, and their modifications due to elevated n-3 PUFA levels was characterized in different organs in healthy mice. Furthermore the role of murine 15-lipoxygenase as well as omega-6 docosapentaenoic acid-derived 17-hydroxydocosapentaenoic acid (17-HDPAn-6) and 10,17-dihydroxydocosapentaenoic acid (10,17-HDPAn-6) in experimental colitis was investigated. In the first study, the profile of monohydroxy lipid metabolites in heart, lung, liver, colon, kidney, spleen and skeletal muscle of healthy wildtype mice were characterized using liquid chromatographyâmass spectrometry. We found distinct characteristic lipid metabolite patterns in different organs. Elevated n-3 PUFA levels in transgenic fat-1 mice lead to increased formation of n-3 PUFA derived metabolites. Eicosapentaenoic acid â even though levels were low - was strongly utilized for formation of 12-HEPE in the lung as well as spleen and 9-HEPE and 18-HEPE in the other organs. The second study showed that higher n-3 PUFA levels could be achieved through dietary intervention with a diet enriched with n-3 PUFA compared to the fat-1 mouse model. This was reflected by increased levels of n-3 PUFA derived lipid metabolites. In plasma of mice fed with an enriched n-3 PUFA diet the lipid metabolite profile was dominated by metabolites derived from the LOX and CYP450 pathways. The anti-inflammatory effect of 17-HDPAn-6 and 10,17-HDPAn-6 in dextran sodium sulfate (DSS)-induced colitis was examined in the third study. Intraperitoneal injection of 17-HDPAn-6 or 10,17-HDPAn-6 alleviated DSS-colitis, epithelial damage and macrophage infiltration. Furthermore 17-HDPAn-6 and 10,17-HDPAn-6 increased phagocytosis activity in macrophage cell line RAW 264.7. The role of murine 15-lipoxgenase (Alox15) in DSS-colitis was explored in the fourth study. Alox 15 expression was augmented in wildtype C57BL/6 mice with DSS-colitis. Furthermore, systemic inactivation of the Alox15 gene (Alox15â/â) was associated with less severe colitis signs and preserved function of the intestinal barrier. Lower 12-hydroxyeicosatetraenoic acid (12-HETE) levels were detected in Alox15â/â mice with DSS-colitis. 12-HETE impaired intestinal epithelial barrier function in vitro in CaCo-2 cells. The results indicate a protective effect of systemic Alox15 inactivation, which might be related to reduced formation of 12-HETE, as well as of the lipid mediators 17-HDPAn-6 and 10,17-HDPAn-6 in the context of DSS-colitis.Langkettige mehrfach ungesĂ€ttigte Omega-3 und Omega-6 FettsĂ€uren stellen VorlĂ€ufer fĂŒr bioaktive Lipidmediatoren und â metabolite dar, welche enzymatisch ĂŒber Cyclooxygenasen, Lipoxygenasen (LOX), Cytochrome P450 (CYP-450) sowie Autooxidationsprozessen synthetisiert werden, und können in ihrer Bildung pharmakologisch beeinflusst werden. In den dieser Arbeit zugrundeliegenden Publikationen wurde der Einfluss von erhöhten Omega-3 FettsĂ€urespiegeln auf die Zusammensetzung des Lipidmediatorenprofils, insbesondere der einfach hydroxylierten Metabolite HydroxyeicosatetraensĂ€uren, HydroxyeicosapentaensĂ€uren (HEPE) sowie HydroxydocosahexaensĂ€uren, in verschiedenen Organen der Maus untersucht. Weiterhin wurde die Rolle der murinen 15-Lipoxygenase sowie der von Omega-6 DocosapentaensĂ€ure stĂ€mmigen Lipidmetabolite 17-HydroxydocosapentaensĂ€ure (17-HDPAn-6) und 10,17-DihydroxydocosapentaensĂ€ure (10,17-HDPAn-6) im Kontext eines experimentellen Kolitismodells untersucht. In der ersten Studie wurde mittels FlĂŒssigchromatographie mit Massenspektrometrie-Kopplung die Zusammensetzung von Monohydroxy-Lipidmetaboliten in Herz, Lunge, Leber, Kolon, Nieren, Milz und Skelettmuskel der Maus charakterisiert. Es fand sich eine organ- und gewebespezifische Verteilung der untersuchten Monohydroxy-Lipidmetabolite. Ein erhöhter Omega-3 FettsĂ€urespiegel in der transgenen fat-1 Maus fĂŒhrte zu einem organ- und gewebespezifischen Anstieg der Omega-3 FettsĂ€ure stĂ€mmigen Lipidmetabolite. EicosapentaensĂ€ure wurde trotz geringer Mengen hocheffizient zu hauptsĂ€chlich 12-HEPE in der Lunge sowie Milz und 9-HEPE und 18-HEPE in den anderen Organen verstoffwechselt. In der zweiten Studie konnte gezeigt werden, dass durch diĂ€tetische Intervention mittels Omega-3 FettsĂ€ure angereichertem Futter ein höherer Omega-3 FettsĂ€urespiegel im Vergleich zum transgenen fat-1 Mausmodell erzielt wurde. Es fanden sich entsprechend erhöhte Spiegel der von Omega-3 FettsĂ€uren abgeleiteten Lipidmetabolite. Im Plasma von MĂ€usen auf Omega-3 FettsĂ€urereichem Futter wurde das Lipidmetabolitenprofil von LOX und CYP-450 Enzymen synthetisierten Lipidmetaboliten dominiert. Der anti-inflammatorische Effekt von 17-HDPAn-6 und 10,17-HDPAn-6 wurde in der dritten Studie im Dextran Natriumsulfat (DSS)-induzierten Kolitismodell in wildtyp C57BL/6 MĂ€usen untersucht. Eine intraperitoneale Behandlung mit 17-HDPAn-6 oder 10,17-HDPAn-6 milderte die DSS-Kolitis, den epithelialen Schaden sowie die Makrophageninfiltration. Weiterhin erhöhte 17-HDPAn-6 sowie 10,17-HDPAn-6 in der Makrophagen-Zelllinie RAW 264.7 die PhagozytoseaktivitĂ€t. Die Rolle der murinen 15-Lipoxygenase (Alox15) wurde in der vierten Studie im DSS-Kolitismodell untersucht. Unsere Ergebnisse zeigen eine erhöhte Alox15 Expression in wildtyp MĂ€usen mit DSS-Kolitis. Eine systemische Inaktivierung des Alox15 Genes (Alox15â/â) war mit einer signifikant milderen KolitisaktivitĂ€t und einer erhaltenen Funktion der intestinalen Barriere assoziiert. In Alox15â/â MĂ€usen mit DSS-Kolitis wurden verminderte 12-HydroxyeicosatetraensĂ€ure (12-HETE) Spiegel gemessen. In vitro Experimente konnten zeigen, dass 12-HETE die epitheliale Barriere in CaCo-2 Zellen stört. Die Ergebnisse weisen auf einen protektiven Effekt der systemischen Alox15 Inaktivierung, möglicherweise bedingt durch eine verminderte Synthese von 12-HETE, sowie der Lipidmediatoren 17-HDPAn-6 und 10,17-HDPAn-6 im DSS-Kolitismodell hin
The Emergence of the Legitimacy of Religious Healing Knowledge in Taiwan
This dissertation investigates how religious healing knowledge has been defined and used by scholars, physicians, and New Agers and how religious healing knowledge emerged as a legitimate area of knowledge in Taiwan. The key position of religious healing knowledge within the entanglement between religion and spirituality is also examined. After the martial law was lifted in 1987, Taiwanâs society had rapidly diversified, and its religions were at the transition point between the old and the new. Meanwhile, the new spirituality culture was introduced into Taiwan in the 1980s and got popular in the 1990s, and it inherited the trend of religious individuality and the orientation of syncretism. Results in this dissertation showed that the concept of âspiritualityâ had its particularity in the context of Taiwan. Although there was a continuity between religion and spirituality, the concept of âspiritualityâ was not stabilized in Taiwan, giving actors like scholars, physicians, and New Agers an operating space to do knowledge production and connect differentiated knowledges. They regarded religious healing knowledge as a resource for knowledge translation, which made its legitimacy had gradually emerged. The scholarsâ interest was to indigenize academic knowledge, and they mobilized religious healing knowledge to connect foreign and local knowledge; the conceptual distinction between disease and illness was important to them. The physiciansâ interest was to find other healing methods to supplement the deficiencies of Western medicine, and they mobilized religious healing knowledge to connect CAM and Western medicine; the conceptual distinction between cure and healing was important to them. New Agersâ interest was to seek spirituality that is different from traditional religions, and they mobilized religious healing knowledge to construct a flexible, hybrid cosmology in order to connect foreign and local healing knowledge; the conceptual distinction between religion and spirituality was important to them. The three concepts of illness, healing, and spirituality were more flexible than concepts of disease, cure, and religion. They provided these actors a space for operation in their knowledge production. The legitimacy of religious healing knowledge was brought out through their knowledge production
In search of Lin Zhao\u27s soul = ć°æŸææçéé
Film Director: Hu Jie (èĄæ°)
Film Release Year: 2004https://commons.ln.edu.hk/ccs_worksheet/1001/thumbnail.jp
Umbilic hypersurfaces of constant sigma-k curvature in the Heisenberg group
We study immersed, connected, umbilic hypersurfaces in the Heisenberg group
with We show that such a hypersurface, if closed, must
be rotationally invariant up to a Heisenberg translation. Moreover, we prove
that, among others, Pansu spheres are the only such spheres with positive
constant sigma-k curvature up to Heisenberg translations.Comment: 28 pages, 6 figure
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