Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines

In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies). We report here that injection of naked -globin untranslated region (UTR)-stabilized mRNA coding for -galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the requirement of antiviral, antibacterial or antitumor immunity.Received 14 June 2004; received after revision 19 July 2004; accepted 9 August 2004     

Angiogenesis and signal transduction in endothelial cells

Endothelial cells receive multiple information from their environment that eventually leads them to progress along all the stages of the process of formation of new vessels. Angiogenic signals promote endothelial cell proliferation, increased resistance to apoptosis, changes in proteolytic balance, cytoskeletal reorganization, migration and, finally, differentiation and formation of a new vascular lumen. We aim to review herein the main signaling cascades that become activated in angiogenic endothelial cells as well as the opportunities of modulating angiogenesis through pharmacological interference with these signaling mechanisms. We will deal mainly with the mitogen-activated protein kinases pathway, which is very important in the transduction of proliferation signals; the phosphatidylinositol-3-kinase/protein kinase B signaling system, particularly essential for the survival of the angiogenic endothelium; the small GTPases involved in cytoskeletal reorganization and migration; and the kinases associated to focal adhesions which contribute to integrate the pathways from the two main sources of angiogenic signals, i.e. growth factors and the extracellular matrix.Received 13 February 2004; received after revision 25 March 2004; accepted 19 April 2004     

Eine neue Gruppe hochwirksamer Lokalanästhetika

Summary Highly active and relatively little toxic local anesthetics from the group of diethylaminoethylesters of alkoxydiphenylcarbamic acids were developed. The substances were tested for local anesthetic activity in surface and infiltration anesthesia.     

Reversal of the inhibitory effect of (2-chloroethyl)trimethyl-ammonium Chloride on the Flowering ofChenopodium rubrum L. by Kinetin

Zusammenfassung Chlorcholinchlorid (CCC) (2 × 10^–3 M) hemmt die Blühinduktion bei der KurztagspflanzeChenopodium rubrum L. Es wird gezeigt, dass diese Hemmung nicht nur durch Gibberellinsäure, sondern auch durch Kinetin (1 mg/l) aufgehoben werden kann. Eine Behandlung mit Kinetin derselben Konzentration allein (ohne vorherige Applikation von CCC) blockiert die Blühinduktion beiC. rubrum fast vollständig. Der Mechanismus der CCC-Wirkung auf die Blühinduktion wird diskutiert.     

Stimulation of pyruvate carboxylation by gastric secretagogues

Summary Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.This investigation was supported by Consejo de Desarrollo Científico y Humanístico de la Universidad del Zulia, and by CONICIT Grant S1-0455.     

The influence of cobalt on the endoplasmatic reticulum of the horse bean (Vicia faba L.)

Summary The exogeneous application of cobalt induces the differentiation of membrane complexes of the endoplasmic reticulum. After longer acting of cobalt these membranes are dilated and later destroyed. This fact can manifest itself also in some disturbances of the cell division.