Design of a short membrane-destabilizing peptide covalently bound to liposomes.

We characterized the physical and biological properties of a 14-residue amphipathic sequence called SFP (for short fusogenic peptide). At acidic pH, this short synthetic peptide interacts with various phospholipidic monolayers. These interactions were correlated with a pH-dependent conformational transition of SFP resulting in a hydrophobic alpha-helical structure. The hemolysis assay showed a pH-dependent weak membrane destabilizing activity of SFP. However, membrane anchoring of SFP through a covalently bound myristic acid enhanced by 1000-fold its membrane-destabilizing power. Moreover, SFP covalently bound to fluorescent-labeled liposomes induced a pH-dependent mixing of both membranes. SFP, a small synthetic peptide, is thus able to mimick many aspects of viral protein-induced membrane fusion: conformational change, membrane destabilization, membrane anchoring and finally pH-dependent lipid mixing.

Effects of immuno-potent drugs and their association with an unfractionated heparin on an experimental venous thrombosis.

Immuno-potent drugs are largely used in human medicine. The aim of this study was to determine the role of two immuno-modulators (sodium diethyl-dithiocarbamate, RU 41 740) and two immuno-suppressors (methylprednisolone, cyclosporin A) alone or in association with an unfractionated heparin (Calciparin), on an experimental venous thrombosis made by vena cava ligation in male Wistar rats. Each immuno-potent drug was administered for six days before the thrombus induction at the same dosage (10mg/kg b.w.), and the Calciparin, used as treatment of the thrombosis, was administered two hours after the thrombus induction at the dose of 1mg/kg b.w. Immuno-treatment potentiated thrombus formation: the increase in thrombus weight was greater with immuno-modulators (43% on average in comparison with placebo) than with immuno-suppressors (20%). In association with Calciparin the antithrombotic effect was also potentiated and more marked with the immuno-modulators than with immuno-suppressors. An increase in circulating monocytes was observed in all groups whether Calciparin was present or not. Coagulation tests were not affected by immuno-therapy. However, immuno-modulators led to an inhibition of platelet aggregation. In conclusion, this trial seems to show a probable effect of immunological cells in thrombosis and in the antithrombotic effect of heparin, but the mechanism involved is not yet determined.

The role of essential vitamins in the development of thrombosis and hemorrhage--an experimental study.

To evaluate the action of essential vitamins on hemorrhage, coagulation and thrombosis, a multivitaminized solution was daily administered at three different doses for two weeks to male Wistar rats. Two experimental models were carried out: a venous thrombosis and an induced-hemorrhage model. Results indicate a low thrombogenic effect, a large and dose-dependent decrease of hemorrhage and no effect on coagulation. The observed effects on thrombosis and hemorrhage were not connected with an overdose of vitamins involving many secondary effects, since no blood viscosity parameters were modified. Three main hypotheses are envisaged to explain these results: a direct effect on platelet functions, an action on the leukocytic population, and a possible modification of the vessel wall response. However, further investigations are needed to specify the mechanisms involved.

[How to standardize low molecular weight heparins]. / Quel standard utiliser pour les héparines de bas poids moléculaire?

Heparin, used in anticoagulant and antithrombotic therapeutic for over fifty years, turns out to mean important side effects and serious haemorrhagic risk. The obtaining, from 1976, of the first low molecular weight heparins (LMWH) preparations is partly allowed to overcome those problems. The LMWH present an identical or greater antithrombotic capacity than the unfractioned heparin and mean a lower haemorrhagic risk. Thus their use in antithrombotic therapy is very interesting. However, the existence of different units for the LMWH sets a standardization problem for their clinical use and for their biological follow up. The first international LMWH standard introduction by the World Health Organisation in 1986 may be useful to give a great homogeneity of the interlaboratory results, to serve as reference to the biologists, as activity standardization for the manufacturers or as security for the clinicians. However, it seems its definition mode and its validity call into question by several authors. The anti Xa activity, advocated in the biological surveillance, does not seem to perfectly fit to the LMWH therapy. The debate about the standardization of the low molecular weight heparins keeps open.

[Nitrous oxide in dental anesthesia: facts about its introduction in Spain]. / El óxido nitroso en la anestesia odontológica: datos sobre su introducción en España.

After a free period of twenty years the interest for using nitrous oxide in suppressing pain related to dental surgery has increased since the end of the sixties of the last century. In this work we present the result of our investigations on the person who must be considered the introducer of this technique in Spain: José Meifrén Alfares, odontologist at Barcelona.

[Robert R. Macintosh and Spain: a productive relationship]. / Robert R. Macintosh y España: una relación fecunda.

Through his visit to Spain in 1946, Robert R. Macintosh exercised considerable influence on the introduction and development of modern anesthesia in this country. This paper reviews the technical advances Mackintosh introduced and considers how his visit was one of the most important factors in unleashing the development of the profession here. Also reviewed are the other visits Mackintosh made in the course of his career. Those trips were less important, with the exception of a 1937 visit that inspired the design of the Oxford vaporizer, a technical concept based on simplicity, safety and the anesthesiologist's experience.

[A new toy: upswing in curare use in Spanish anesthesia]. / A new toy: la irrupción del curare en la anestesia española (1946).

The introduction of curare for general anesthesia by Harold Griffith in 1942 was one of the most important moments in the development of anesthesiology. However, several years passed before curare came to be used in Spain. We review the early application of curare and the role played by Robert Macintosh, Professor of Anaesthesia at Oxford, in introducing the drug to Spain.

[María Oliveras: pioneer of neuroanesthesia in Catalonia]. / María Oliveras: pionera de la neuroanestesia en Cataluña.

María Oliveras Collelmir (1910) was the first woman to practice anesthesiology in Catalonia and one of the first physicians to receive formal training in the specialty at the important Nuffield Department of Anaesthetics in Oxford. She pioneerèd the use of general anesthesia with tracheal intubation for neurosurgery. This article relates how Dr. Oliveras introduced general anesthesia with endotracheal intubation for neurosurgery in Catalonia and pays well-deserved homage to this enterprising woman, who overcame family obstacles and social prejudices of the time to become the first female anesthesiologist in Catalonia.

A new cationic liposome encapsulating genetic material. A potential delivery system for polynucleotides.

The endeavour to enhance gene therapy has led to increased research on the development of simple, efficient and safe delivery systems. This study deals with the use of an artificial cationic lipid on the encapsulation of genetic material in liposomes. The addition of a biologically degradable cationic phospholipid, dipalmitoyl-L-alpha-phosphatidylethanolamine covalently coupled to L-lysine, in a standard liposome formulation allowed us to obtain vesicles with high entrapment of various polynucleotides. Polynucleotide degradation by nucleases is markedly prevented by these liposomes. The preparations were stable in both culture medium and human plasma. This latter finding is consistent with the weak binding of plasma proteins on the liposome surface. The efficiency of this new delivery system was demonstrated in antiviral assays. Finally, these liposomes displayed a relatively low cellular toxicity. All these findings indicate that these cationic vesicles are very suitable for genetic material vehiculation.