Impairment of rat postnatal lung alveolar development by glucocorticoids: involvement of the p21CIP1 and p27KIP1 cyclin-dependent kinase inhibitors

It has been shown that glucocorticoids accelerate lung development by limiting alveolar formation resulting from a premature maturation of the alveolar septa. Based on these data, the aim of the present work was to analyze the influence of dexamethasone on cell cycle control mechanisms during postnatal lung development. Cell proliferation is regulated by a network of signaling pathways that converge to the key regulator of cell cycle machinery: the cyclin-dependent kinase (CDK) system. The activity of the various cyclin/CDK complexes can be modulated by the levels of the cyclins and their CDKs, and by expression of specific CDK inhibitors (CKIs). In the present study, newborn rats were given a 4-d treatment with dexamethasone (0.1-0.01 microg/g body weight dexamethasone sodium phosphate daily on d 1-4), or saline. Morphologically, the treatment caused a significant thinning of the septa and an acceleration of lung maturation on d 4. Study of cyclin/CDK system at d 1-36 documented a transient down-regulation of cyclin/CDK complex activities at d 4 in the dexamethasone-treated animals. Analysis of the mechanisms involved suggested a role for the CKIs p21CIP1 and p27KIP1. Indeed, we observed an increase in p21CIP1 and p27KIP1 protein levels on d 4 in the dexamethasone-treated animals. By contrast, no variations in either cyclin and CDK expression, or cyclin/CDK complex formation could be documented. We conclude that glucocorticoids may accelerate lung maturation by influencing cell cycle control mechanisms, mainly through impairment of G1 cyclin/CDK complex activation.

Bongars Quellenwerk zur Geschichte der Kreuzzüge

ln seinen letzten Lebensjahren gab Jacques Bongars (1554-1612) unter dem Titel Gesta Dei per Francos (Gottes Taten durch die Franken) eine zweibändige Sammlung von mittelalterlichen Texten zu den Kreuzzügen heraus, die 1611 im Verlagshaus Wechel in Hanau erschien. Er stellte in seinem Quellenwerk gegen zwanzig Texte verschiedenster Autoren zusammen, von denen viele zum ersten Mal überhaupt gedruckt wurden. Der zweite Band enthält ausschliesslich die Geschichte der Kreuzzüge des Venezianers Marino Sanudo d. Ä. (ca. 1270-ca. 1343). Diese Schrift mit dem Titel Liber secretorum fidelium crucis ist wissenschaftsgeschichtlich bedeutend aufgrund der darin enthaltenen Karten: einer Weltkarte, einer Karte von Ägypten (bzw. des östlichen Mittelmeeres und des Roten Meeres), einer Karte des Heiligen Landes sowie der Stadtpläne von Akkon und Jerusalem.