Biomedical subjects

R Bossa

Publications and source records attributed to R Bossa.

At least 73 records · Page 4Linked to original sources

PubMedDate not supplied

Reduction of 4-epiadriamycin cardiotoxicity by milrinone, a new cardiotonic agent.

Recently, several non-catecholamine, non-glycoside cardiotonic drugs have been described. New compounds include amrinone, sulmazole and milrinone. Milrinone, a close analogue of amrinone, is about 30 times more potent than amrinone. In attempts to alleviate anthracyclines toxicity, we have previously reported that amrinone and sulmazole reduced the negative inotropic effect of adriamycin and 4-epiadriamycin in isolated guinea pig atria. The present study reports the effects of 4-epiadriamycin on electrically driven isolated guinea pig left atrium, in normodynamic or hypodynamic conditions. Exposure for 60' to 4-epiadriamycin (100 micrograms/ml) caused a depression of contractile force and of maximal rate of contractile force (df/dt). The negative effects of 4-epiadriamycin are antagonized by milrinone at 20 micrograms/ml.

Animals↗

PubMedDate not supplied

Cytotoxic activity of a series of heteroaryl-ONN-azoxy-sulphones and aryl sulphonylhydrazones.

Synthesis of heteroaryl-ONN-azoxysulphones and pyrazolyl-ONN-azoxycyanides was carried out by the action of the appropriate reagents on the corresponding nitroso derivatives. Pyrazolyl-ONN-azoxyamides were obtained by hydrolysis of the corresponding cyanides. Synthesis of the arylsulphonylhydrazones was carried out by reacting R-substituted phenyl-sulphonylhydrazines on the isomers of methylfuroxancarbaldehyde. Cytotoxic activity was assessed on HeLa cells. Some of the compounds tested inhibit the colony-forming ability of the tumor cells at low concentrations.

Antineoplastic Agents↗

PubMedDate not supplied

Cytotoxic activity of aryl and heteroaroxylazoxy derivatives.

Synthesis of aryl and heteroarylazocyanides, azoxyesters and azoxysulphones, was carried out by the action of appropriate reagents on the corresponding nitroso derivatives and arylazoxyamides were obtained by hydrolysis of the corresponding azoxycyanides. Cytotoxic activity was assessed utilizing cultured P388 leukemia cells. Most of the compounds tested showed a marked cytotoxicity at concentrations below 1 micrograms/ml.

Animals↗

PubMedDate not supplied

Sensitivity to anthracyclines in P388/dx leukaemia cells.

It has been demonstrated previously that neoplastic cells with reduced oxygen consumption are more sensitive to doxorubicin8. We have examined the relationship between doxorubicin sensitivity and oxygen consumption of P388 murine leukaemia cell line (P388) and of a doxorubicin resistant subline (P388/dx). Oxygen utilization by P388/dx cells was higher than that found in the sensitive line. A variety of calcium antagonists, including channel blockers and intracellular antagonists (verapamil, trifluoperazine, dantrolene, TMB-8, nitrendipine) or membrane acting drugs (lucensomycin), enhanced the cytotoxic activity of doxorubicin in P388 and markedly in P388/dx subline. This action was accompanied by a reduction of oxygen consumption more pronounced in the resistant cells. These findings emphasizé the correlation between oxygen uptake, instead of calcium dependent processes, and doxorubicin responsiveness. The calcium ionophores A 23187 failed to alter doxorubicin activity in P388 and P388/dx leukaemia.

Animals↗

PubMedDate not supplied

Effect of adriamycin on myocardial contractility and on the action of antibiotic ionophores.

In the isolated guinea pig atria adriamycin exerted a negative inotropic effect; calcium ionophores A23187 and X537A increased the force of contraction. In the presence of adriamycin only the positive inotropic effect of ionophore A23187 was significantly reduced. It may be deduced that adriamycin shows its negative inotropic effect by inhibiting the entry of extracellular Ca++ into the myocardial cells and the release of Ca++ from intracellular stores.

Animals↗

PubMedDate not supplied

Reduction of anthracycline cardiotoxicity by amrinone and sulmazole.

In attempts to alleviate or prevent anthracycline toxicity, we have recently reported that amrinone and sulmazole markedly reduce the negative inotropic effect of adriamycin and 4-epiadriamycin in isolated spontaneously beating guinea pig atria in normodynamic or hypodynamic conditions. Amrinone and sulmazole are non catecholamine, non glycoside agents with inotropic properties. The present study reports the effects of adriamycin and 4-epiadriamycin (100 micrograms/ml) on electrically driven isolated guinea pig left atrium in normodynamic or hypodynamic conditions. Exposure for 60' to the two drugs caused a depression of contractile force and of maximal rate of contractile force (df/dt). The cardiac depressant effect of adriamycin as shown previously on spontaneously beating atria does not differ from that of 4-epiadriamycin. The negative effects of the two antitumor drugs are antagonized by amrinone (200 micrograms/ml) and sulmazole (100 micrograms/ml).

Amrinone↗

PubMedDate not supplied

Anthracyclines cardiotoxicity: antagonism by sulmazole, a new cardiotonic agent.

In attempts to alleviate or prevent anthracyclines toxicity, we have recently reported that amrinone markedly reduced the negative inotropic effect of adriamycin in isolated guinea pig atria, in normodynamic or hypodynamic conditions (medium with reduced calcium content). Previous experiments on isolated guinea pig atria showed that the negative inotropic action of anthracyclic compounds was enhanced in hypodynamic conditions. The present study reports the effects of 4-epiadriamycin on spontaneously beating guinea pig atria, in normo- or hypodynamic conditions. 4-Epiadriamycin (100 micrograms/ml) exerts a negative inotropic and chronotropic effect which matches that of adriamycin. The negative effects of the two antitumoral drugs are antagonized by sulmazole, a benzimidazole derivative with cardiotonic activity. In contrast to cardiac glycosides, the new compounds (amrinone, sulmazole, and derivatives) could be experimented in an attempt to antagonize the toxicity of anthracyclic compounds.

Aminopyridines↗

PubMedDate not supplied

New alkylating agents: butyrophenone derivatives.

The antimitotic properties associated with the bis (2-chloroethyl) amino group are well known, a number of compounds bearing this group being of therapeutic interest. The choice of a suitable supporting moiety for this group is important. Our experiments on a butyrophenone derivative, ketocaine, which possesses local anesthetic activity, showed that this drug is able to modify the oxygen consumption by tissues with prevailing anaerobic metabolism and to inhibit the mitotic activity of human lymphocytes in culture stimulated by phytohemagglutinin. These observations prompted us to prepare compounds by the general formula reported in Tables I and II. All compounds were tested in mice implanted i.p. with 10(6) Ehrlich ascites tumour cells. After 24 h the animals were treated with a single dose of the compound. The antitumor activity was correlated with: position (2, 4) and length (n = 0-2) of the chain with carbonyl group; presence (R' = H, ND2) and position (2, 4) of nitro group; monofunzional or bifunzional compound. Some of these show a potent antitumor activity.

Alkylating Agents↗

PubMedDate not supplied

In vitro and in vivo studies with anionic sulfatide-liposomes containing adriamycin.

Neutral and negatively charged liposomes containing Adriamycin (ADM) were examined for efficiency of drug entrapment and stability in serum. The greatest entrapment of ADM was obtained with negatively charged liposomes containing sulfatide. Moreover, these sulfatide-containing liposomes were more stable than other liposomes in the presence of serum. Tissue distribution studies indicated that the levels of ADM were increased several-fold in mouse liver and spleen after i.v. injection of the drug entrapped in sulfatide-liposomes, while levels of the drug were significantly diminished in the heart. Finally, the in vivo antitumor activity of ADM in liposomes containing sulfatides resulted in significantly greater survival rates than free ADM or ADM entrapped in liposomes without sulfatides.

Animals↗

PubMedDate not supplied