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Biomedical subjects

F Ledda

Publications and source records attributed to F Ledda.

130 records · Page 8Linked to original sources
PubMedDate not supplied

Electrophysiological and antiarrhythmic properties of propafenon in isolated cardiac preparations.

Propafenon, a new antiarrhythmic drug, caused a 30% decrease in maximal driving frequency and a 65 ms net increase in functional refractory period of isolated guinea pig atria at a concentration as low as 0.5 microgram/ml. The spontaneous rate of isolated atria and the contractility of electrically driven ventricular strips were reduced after treatment with propafenon 1 microgram/ml. Propafenon 0.5 microgram/ml also altered action potentials of sheep Purkinje fiber. It reduced the action potential and overshoot amplitudes, decreased the maximum rate of depolarization of the action potential upstroke in a frequency-dependent fashion, shortened the action potential and effective refractory period, and depressed the membrane responsiveness. Moreover, propafenon antagonized the chronotropic and inotropic effects of isoprenaline in isolated guinea pig heart preparations; the pA2 value was about 6.4. Finally, propafenon possessed very weak calcium antagonist properties, being about 100 times less potent than verapamil in this respect. We conclude that propafenon is an antiarrhythmic drug with beta-adrenoceptor blocking and "membrane stabilizing" activities in the same range of concentrations and that it has a calcium antagonistic activity only at much higher concentrations.

Action Potentials↗
PubMedDate not supplied

Endostatin: a promising drug for antiangiogenic therapy.

Angiogenesis, the formation of new blood vessels from existing capillaries, is critical for tumors to grow beyond a few in size. Tumor cells produce one or more angiogenic factors including fibroblast growth factor and vascular endothelial growth factor. Surprisingly, antiangiogenic factors or angiogenesis inhibitors have been isolated from tumors. Some angiogenesis inhibitors, such as angiostatin, are associated with tumors while others, such as platelet-factor 4 and interferon-alpha are not. Endostatin, a C-terminal product of collagen XVIII, is a specific inhibitor of endothelial cell proliferation, migration and angiogenesis. The mechanism by which endostatin inhibits endothelial cell proliferation and migration is unknown. Endostatin was originally expressed in a prokaryotic system and, late, in a yeast system, thanks to which it is possible to obtain a sufficient quantity of the protein in a soluble and refolded form to be used in preclinical and clinical trials.

Angiogenesis Inhibitors↗
PubMedDate not supplied

The potent relaxant effect of adenosine in rabbit corpora cavernosa is nitric oxide independent and mediated by A2 receptors.

In the present study the effect of adenosine and adenosine analogues on rabbit isolated cavernosal smooth muscle has been evaluated in comparison with the effect of acetylcholine and electrical field stimulation. In the presence of guanethidine and indomethacin, acetylcholine and electrical field stimulation relaxed the rabbit corpus cavernosum, which was precontracted with phenylephrine. The nitric oxide synthesis inhibitor, N omega-nitro-L-arginine-methylester (L-NAME), greatly reduced the relaxation induced by electrical stimulation and completely abolished the relaxant effect of acetylcholine. A concentration-dependent relaxation of the rabbit corpus cavernosum was produced by adenosine; this effect was not modified by L-NAME, but was reduced by adenosine deaminase. On the other hand, the adenosine-induced relaxation was potentiated by the inhibitor of adenosine deaminase, erythro-9-(2-hydroxy-3-nonyl)adenine and by the adenosine uptake inhibitor dipyridamole. Moreover, the effect of adenosine was antagonized by the unspecific adenosine receptor antagonist 8-phenyltheophylline. The receptor subtypes involved in cavernosal relaxation were characterized by using selective receptor antagonists: 1,3-dipropyl-8-cyclopentylxanthine, a blocker of A, receptors, did not modify adenosine-induced relaxation. This effect was, however, antagonized by the A2-receptor antagonist CGS15943. A relaxant effect was also obtained with nanomolar concentrations of two synthetic adenosine analogues, the preferential A2 receptor agonist 5'-N-ethylcarboxamidoadenosine and the A2a selective agonist CGS21680. These results demonstrated that adenosine has potent relaxant activity on the corpus cavernosum, acting through a mechanism different from the nitric oxide pathway, and that receptors involved in the effect of adenosine belong to the A2a subtype.

Acetylcholine↗