Molecular events that result in loss of pain perception are poorly understood in diabetic neuropathy. Our results show that the receptor for advanced glycation end products (RAGE), a receptor ...associated with sustained NF-kappaB activation in the diabetic microenvironment, has a central role in sensory neuronal dysfunction. In sural nerve biopsies, ligands of RAGE, the receptor itself, activated NF-kappaBp65, and IL-6 colocalized in the microvasculature of patients with diabetic neuropathy. Activation of NF-kappaB and NF-kappaB-dependent gene expression was upregulated in peripheral nerves of diabetic mice, induced by advanced glycation end products, and prevented by RAGE blockade. NF-kappaB activation was blunted in RAGE-null (RAGE(-/-)) mice compared with robust enhancement in strain-matched controls, even 6 months after diabetes induction. Loss of pain perception, indicative of long-standing diabetic neuropathy, was reversed in WT mice treated with soluble RAGE. Most importantly, loss of pain perception was largely prevented in RAGE(-/-) mice, although they were not protected from diabetes-induced loss of PGP9.5-positive plantar nerve fibers. These data demonstrate, for the first time to our knowledge, that the RAGE-NF-kappaB axis operates in diabetic neuropathy, by mediating functional sensory deficits, and that its inhibition may provide new therapeutic approaches.
Molecular events that result in loss of pain perception are poorly understood in diabetic neuropathy. Our results show that the receptor for advanced glycation end products (RAGE), a receptor ...associated with sustained NF-κB activation in the diabetic microenvironment, has a central role in sensory neuronal dysfunction. In sural nerve biopsies, ligands of RAGE, the receptor itself, activated NF-κBp65, and IL-6 colocalized in the microvasculature of patients with diabetic neuropathy. Activation of NF-κB and NF-κB–dependent gene expression was upregulated in peripheral nerves of diabetic mice, induced by advanced glycation end products, and prevented by RAGE blockade. NF-κB activation was blunted in RAGE-null (RAGE
–/–
) mice compared with robust enhancement in strain-matched controls, even 6 months after diabetes induction. Loss of pain perception, indicative of long-standing diabetic neuropathy, was reversed in WT mice treated with soluble RAGE. Most importantly, loss of pain perception was largely prevented in RAGE
–/–
mice, although they were not protected from diabetes-induced loss of PGP9.5-positive plantar nerve fibers. These data demonstrate, for the first time to our knowledge, that the RAGE–NF-κB axis operates in diabetic neuropathy, by mediating functional sensory deficits, and that its inhibition may provide new therapeutic approaches.
Das Logion in Lk 11,34–36 bleibt im literarischen Zusammenhang des Evangeli-ums sperrig, weil der situative Kontext nicht tradiert wurde. Während Lk 11,34 den Einfluss der moralischen Disposition auf ...die anatomische Sehfähigkeit beschreibt, thematisiert Lk 11,35–36 die Kompensation der fehlenden Sehfähigkeit durch die richtige innere Haltung, zur Sprache gebracht als τὸ φῶς τὸ ἐν σοί. Unter Einbindung von Lk 11,21–22 und Lk 12,15 sowie Lk 11,29–30 lässt sich als möglicher situativer Kontext die Ansprache eines blinden Gegenübers annehmen, dessen vermeintliche Bedürftigkeit mit der Besitzstandswahrung ei-ner ökonomisch etablierten Gruppe kontrastiert wurde. Bedeutsam für die Rezeption könnte das Logion werden, wo es als Hinweis auf die Anerkenntnis einer körperlichen oder geistigen Andersartigkeit und die allen gemeinsame Verantwortung gewertet wird.
Zu Wasser und zu Land Schmidt, Karl Matthias
Millennium (Berlin, Germany),
2/2017, Letnik:
14, Številka:
1
Journal Article
Recenzirano
The paper lines up with studies that discuss the impact of the Jewish War and Vespasian’s advancement on the composition of the Gospel According toMark. Its topic is to show that Mk 4,35-41 and Mk ...5,1-20 form a structural unity that insinuates the idea of a Christian peace, distinguished from Roman warfare and peace. Following those scholars who read Mk 5,1-20 as an allusion to the legio X Fretensis it is argued that Mk 4,35-41 and Mk 5,1-20 are tied together in light of the Roman peace propaganda that claimed apeace by land and by sea - as did Vespasian after the civil war, when he reminded the Romans of Octavian’s victory at fretum Siculum.
Die erste Missionsreise diente Lukas dazu, seinen Protagonisten trotz dessen zwielichtiger Vergangenheit erzählerisch als Helden aufzubauen. Dafür sprechen nicht nur die Gegenüberstellung des ...einstigen Verfolgers und des Magiers Barjesus sowie die Parallelisierung der ersten Schritte von Petrus und Paulus auf dem Weg zu einer erfolgreichen Mission, sondern auch die Zuspitzung einer Verfolgungssituation, in der Paulus erleidet, was er der Gemeinde als Verfolger angetan hat. Ayant participé au premier voyage missionnaire, Luc présente le protagoniste de son récit, malgré son passé douteux, comme un héros. Aussi observet-on tout d'abord, la confrontation entre l'ancien persécuteur et le magicien Barjésus; ensuite, le parallélisme entre les premières étapes des missions de Pierre et de Paul; et enfin, la détérioration de la situation de persécution dans laquelle Paul endure, lui aussi, les souffrances qu'il avait auparavant infligées à la communauté chrétienne.
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