Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2.

Exposure of biological membranes to reactive oxygen species creates a complex mixture of distinct oxidized phospholipid (OxPL) species, which contribute to the development of chronic inflammatory diseases and metabolic disorders. While the ability of OxPL to modulate biological processes is increasingly recognized, the nature of the biologically active OxPL species and the molecular mechanisms underlying their signaling remain largely unknown. We have employed a combination of mass spectrometry, synthetic chemistry, and immunobiology approaches to characterize the OxPL generated from the abundant phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and investigated their bioactivities and signaling pathways in vitro and in vivo. Our study defines epoxycyclopentenones as potent anti-inflammatory lipid mediators that mimic the signaling of endogenous, pro-resolving prostanoids by activating the transcription factor nuclear factor E2-related factor 2 (Nrf2). Using a library of OxPL variants, we identified a synthetic OxPL derivative, which alleviated endotoxin-induced lung injury and inhibited development of pro-inflammatory T helper (Th) 1 cells. These findings provide a molecular basis for the negative regulation of inflammation by lipid peroxidation products and propose a novel class of highly bioactive compounds for the treatment of inflammatory diseases.

Allerunterthänigst-Rechts begründete Additional-Anzeig Ad Exhibitum de 23. Julij nup. und Bitt pro clem.mè demandanda[m] illius celere Relatione, Petitóque deferendo : An Die Römis. Kayserl. ... Majestät [et]c. ; In Sachen Judenschafft zu Franckfurth Contra E. E. Magistrat daselbst ; Bey höchst-preißlichen Reichs-Hof-Rath Den 28. Sept. 1714 übergeben ; Mit Beylagen Num. 1, 2 & 3 ; Rescripti das Bau-Weesen betreffend

Intervenientischer Burgerschafft

Allerunterthänigst-gründliche Gegen-Information Und Exceptiones Sub- & Obreptionis : An Die Römis. Kayserl. ... Majestät ... Auff das am 12. May nup. und 19. currentis mensis erlassene Kayserl. Rescript, Juncta Petitione Humillima Pro Clementissima cassatione ejusdem ... ; In Sachen Judenschafft zu Franckfurth am Mayn Contrà Den Magistrat daselbsten ; Bey höchst-preyßlichen Reichs-Hof-Rath Den 23. Julii 1714 übergeben ; Mit Beylagen A, B, C & D ; Das Bau-Weesen betreffend

Burgerschafftl. Abgeordneter [Johann Dieterich Notebohm ; Joachim Hoppe] [[Elektronische Ressource]]

Scheduled versus Pro Re Nata Dosing in the VIEW Trials

PURPOSE To analyze visual acuity (VA) outcomes before and after preplanned treatment regimen change in the VIEW studies at week 52 (W52). DESIGN Multiple post hoc analyses for retrospectively defined subgroups in 2 multicenter, multinational, double-masked trials. PARTICIPANTS Two thousand four hundred fifty-seven neovascular age-related macular degeneration (AMD) patients. METHODS Patients were randomized to treatment with 0.5 mg ranibizumab given monthly, a 0.5-mg or 2-mg intravitreal aflibercept injection given monthly, or 2 mg intravitreal aflibercept given every other month, after 3 initial monthly doses, up to W52. From W52 through W96, patients received their original dosing assignment using a capped pro re nata (PRN) regimen, with defined retreatment criteria based on VA and morphologic signs of disease activity and mandatory dosing at least every 12 weeks. MAIN OUTCOME MEASURES Best-corrected VA (BCVA) and optical coherence tomography assessments were mandatory at all visits from baseline to W96. Outcomes were changes in BCVA and central retinal thickness. Outcomes were evaluated in all patients who completed 2 years of the VIEW studies using the last observation carried forward method for missing data at interim visits. RESULTS After W52, approximately 20% of patients lost 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more across all treatment arms with PRN treatment. Patients who met the retreatment criterion of loss of 5 ETDRS letters or more in the first quarter of the PRN dosing phase did not recover; mean final VA loss across the 4 study arms was -4.4 to -5.8 letters. Outcomes of these patients up to W52 were indistinguishable from those of the overall population. There were no differences between groups in serious ocular adverse events or Anti-Platelet Trialists' Collaboration arterial thromboembolic events through W96. CONCLUSIONS These analyses suggest that there are subgroups of patients for whom VA outcomes in the second year of the VIEW studies were less stable than in the first year and for whom W52 seems to be an important inflection point. Although alternate reasons specific to the nature of the underlying AMD cannot be fully excluded, the switch in treatment regimen at W52 is a plausible explanation.

Haupt-Nachweisung des Grundsteuer-Sollaufkommens in den westlichen Provinzen pro 1849 : in Folge des Grundsteuergesetzes vom 21ten Januar 1839

Welsch (Projektbearbeiter): Vorgesehene Verwendung der veranschlagten Grundsteuereinnahmen des Jahres 1849 in den preußischen Provinzen Rheinprovinz und Westfalen (nach Regierungsbezirken)

Denkschrift die zur Aufbringung des außerordentlichen Staats-Haushalts-Bedarfs erforderlichen Mittel betreffend: Etat pro 1848: Die Bemerkungen über die Finanzlage des Staats und über die Nothwendigkeit der Beschaffung außerordentlicher Hülfsmittel ...

Welsch (Projektbearbeiter): Rechenschaftslegung der Finanzministers Hansemann (Ministerium Auerswald - Hansemann) über die finanzielle Lage des preußischen Staates: aufgrund der zu erwartenden bedeutenden Einnahmeausfälle (geschätzte 8 Millionen Taler) bei gleichzeitigen Mehrausgaben (geschätzte 22,5 Millionen Taler) mußten dem Staatsschatz 13 Millionen Taler entnommen werden. Da sich jedoch trotz alledem noch eine Haushaltslücke von 15 Millionen Talern ergibt, sind Steuererhöhungen unumgänglich. Samt beigefügtem Gutachten des Vereinigten Landtages vom 8. April 1848

Antisemitismus im Mittelalter : ein Wort pro domo

Raphael Strauß