Anthracycline gels. Preparation and some physico-chemical properties.

Gels have been prepared from aqueous solutions of anthracyclines by addition of salts. The gels are thixotropic and thermally reversible. They are stable for several months in the refrigerator and for long times even at room temperature. The gel-solution transition (melting) temperature depends on the concentration of the anthracycline and on the concentration and nature of the added salt. The melting has been followed by 1H-NMR. Only weak intermolecular interactions (stacking and hydrogen bonds) originate the drug network, within which the solvent is entrapped. 1H-NMR and polarimetric data suggest a stacked helical arrangement of the anthracycline molecules. The gelation process is cooperative.

Anthracycline gels. II. Spectroscopic study on doxorubicin-lecithin association products.

Thixotropic and thermally reversible gels have been prepared from doxorubicin-lecithin association products (DL12) by addition of salts to their aqueous solutions. The gel formation and the melting profiles have been followed by several spectroscopic techniques (1H NMR, UV-Vis, Circular Dichroism). The transition temperatures increase as the concentration of both the salt and the DL12 is increased, suggesting a progressive closer approach of the gel forming species. The process of the gel formation is cooperative and causes immobilization of the doxorubicin molecules of DL12.

Antitumor effect and cardiotoxicity of a doxorubicin-lecithin association.

A doxorubicin-lecithin preparation was tested in vitro on B16 melanoma and Lewis lung carcinoma cells, and in vivo on C57BL/6 mice inoculated with 3LL cells. Results obtained demonstrated that the preparation possesses the same antitumor activity as doxorubicin. The cardiotoxicity of doxorubicin and of the doxorubicin-lecithin association were studied for 120 days after the end of the treatments in Wistar rats inoculated once a week for 5 weeks with equivalent doses of the drugs. Myocardial lesions were observed in both the groups of animals, but their severity and extent were reduced in rats treated with the doxorubicin-lecithin association, and their onset was also delayed.

Modified proton relaxation behaviour in erythrocytes from spontaneously hypertensive rats.

The proton NMR parameters of suspensions of erythrocytes from normotensive (MNS and WKY strains) and spontaneously hypertensive (MHS and SHR strains) rats have been compared: a marked difference in the relaxation behaviour has been observed for the two classes of strains. Various factors which may give rise to the difference found in dynamic behaviour are discussed.

Proton NMR study of erythrocytes of essential hypertensives.

Proton NMR studies (saturation transfer experiments and longitudinal relaxation time determinations) indicate that substantial differences exist between erythrocytes of essential hypertensives and normotensive subjects. A higher degree of intracellular organization has been found for the hypertensives and several factors are proposed as contributing to the observed behaviour.

Interactions of ubiquinones with membrane models.

The effect of the insertion of coenzyme Q10 and some of its shorter chain homologues in membrane models (Reverse Micelles, Small Unilamellar Vesicles and Liposomes) has been studied by NMR and IR spectroscopies. By 1H-NMR we have found that the stretched conformation of the isoprenoid side-chain observed in solution is maintained in membrane models. Interaction between the quinonoid moiety of the Q's and the phosphatidic groups of the phospholipids has been evidenced by 31P-NMR. A large effect of this interaction on the water microdynamics and distribution around the charged groups of the phospholipids has been observed by measurements of 1H and 2H relaxation times and by infrared spectra. The 13C-NMR spectra of the backbone of the acyl chains of phospholipids does not seem to be influenced to a noticeable extent by the presence of the Q's.

Nucleotide pool and the proliferative process: an NMR study of the liver regeneration.

The metabolic changes occurring during liver regeneration after partial hepatectomy have been followed by examination of the perchloric extracts by means of NMR spectroscopy. Proton spectra show an abrupt decrease of glycogen, glucose and nucleotides, which are essentially ribonucleotides, in the first hours after hepatectomy. Nucleotides begin to store up again in the third day after hepatectomy, while glucose and glycogen storage builds up from the second day. 31P data evidence a sharp drop of phosphomonoesters, i.e. monophosphosugars (including AMP) and phosphocholine, and phosphodiesters, i.e. GPC and GPE, soon after hepatectomy and a recovery of the initial levels approximately at the 60th hour and a further increase of PDE at later times. The NMR findings are in agreement with the biochemical knowledge of the course of liver regeneration.

[Anesthesiological problems in renal transplantation]. / Problemi anestesiologici nel trapianto renale

The physiopathological changes observed in uraemia are briefly described and an account is given pharmacological considerations relevant to the induction and maintenance of anaesthesia and muscle relaxation, The anaesthesiological management of 20 kidneys transplants (17 from living donors and 3 from cadavers) is explained. Steps taken for intra-operative care and protection of the transplanted organ to aid its function recovery are explained.

The inhibitory action of ketamine on the rat's gastric secretion.

Ketamine exhibited effects on gastric acid secretion total acidity and acid output. Reduction of secretion by ketamine did not appe,r to be significantly different from values obtained with atropine or hexamethonium. In addition to atropine- and hexamethonium-like effects, ketamine also appeared to decrease gastric secretion through a potentiating activity on the sympathetic nervous system. When sympathetic activity was potentiated by cocaine, the antisecretory effect of ketamine appeared to be significantly reduced, compared with that of atropine. Furthermore, after alpha- or alpha- and beta-blockade, ketamine produced similar decreases in secretion, although maximum inhibitory effect was obtained after beta-blockade. Potentiation of adrenergic activity by ketamine seemed to be mediated through alpha-receptors. Histamine H2 receptors did not appear to be involved in the antisecretory action of ketamine.

[Clinical pharmacology aspects of althesin]. / Aspetti di farmacologia clinica dell'Althesin.

The main pharmacokinetic and pharmacodynamic features of althesin are described. Though relatively new, this steroid is now widely employed in anaesthesiological practice. From the pharmacological standpoint, the high therapeutic index of althesin, the fact that its metabolic fate is known, its rapid elimination, and the prompt, complete awakening of patients when it is used mean that it can be reliably employed in all forms of surgery and on all types of patient. The absolute contraindications coincide with those preventing the employment of general anaesthesia in any form, while the relative contraindications, i.e. those involving particular care in its administration, are linked to the presence of diseases interfering with its mechanism and elimination, the existence of allergy, or cardiovascular disorders of a fairly substantial nature. Althesin, in fact, while not responsible for frank cardiovascular changes, cannot be regarded as entirely innocuous. In other words, it is subject to the same limitations as the barbituric and non-barbituric drugs commonly employed in the i.v. induction of anaesthesia.

[Steroid anesthesia in microsurgery of the middle ear]. / L'anestesia steroidea nella micro-chirurgia dell'orecchio medio.

The essential requirements for correct anaesthesia in microsurgery of the middle ear are described and results obtained with an association of Althesin and NLA drugs in 52 stapedectomies, 27 tympanoplasties, and 14 myringoplasties are presented. Althesin was injected i.v. to induce anaesthesia. Maintenance was obtained by means of the continuous venous perfusion of a 10% solution. The usefulness of the association was apparent from the good cardiac stability noted throughout anaesthesia, during which adrenaline was routinely infiltrated via the external meatus. In addition, the manageability of Althesin enabled a modest degree of hypotension to be established during certain stages of the operation. This enabled the intraoperative bleeding that is one of the major snags in this type of surgery to be reduced in some cases. Other benefits related to the degree of postoperative sedation required and the low toxicity of the drugs employed.