Effect of anthracycline drugs on the element content of cultured embryonic rat cardiomyocytes.

The effect of two anthracyclines--doxorubicin hydrochloride (adriamycin, CAS-25316-40-9), and 4'-epidoxorubicin (epirubicin, CAS-56420-45-2), and an anthracenedione, mitoxantrone (CAS-70476-82-3) on the element content of cultured embryonic rat cardiomyocytes was examined by X-ray microanalysis. Adriamycin induced an increase in Ca, P and S, and a decrease in Cl content. Novantrone caused a marked increase in the Na and a decrease in the Cl content, whereas epirubicin did not affect the content of any of the elements examined. In an attempt to prevent the effect of the drugs on the element content of the cells, the cardiomyocytes were incubated with a blocker of the slow Ca channels--verapamil-- and with each of the three drugs. Verapamil only induced an increase in the Ca and a decrease in the S content of the cells. Except for some protective effect on the element content of the cardiomyocytes, which was altered by adriamycin, the results did not indicate any beneficial effect of verapamil added to the other two drugs, as for this aspect of the study.

SEM observations on the effect of anthracycline drugs on cultured newborn rat cardiomyocytes.

The effect of two anthracyclines-doxorubicin hydrochloride (adriamycin) and 4'-epidoxorubicin (epirubicin) and an anthracenedione (novantrone) on the contractibility and surface ultrastructure of newborn rat cardiomyocytes cultured for five days was examined. While the beating rate of the cells was affected only by the anthracyclines, an alteration of the sarcolemma, disruption of the slender processes and swelling of the nuclei and/or the cells was observed following incubation with each of the three drugs for two hours. However, the damage induced by adriamycin was more pronounced than that induced by the other two drugs, when doses extrapolated from those accepted as therapeutic were compared.

The in vitro effect of pirprofen on the surface ultrastructure and function of human platelets.

The in vitro effect of pirprofen (Rengasil), an antiinflammatory agent, on the surface ultrastructure and function of human platelets was examined and compared with that of acetylsalicylic acid (Aspirin, ASA), and diclofenac sodium (Voltaren, DS). Incubation with pirprofen induced formation of long, needle-shaped pseudopodia, a phenomenon observed also after incubation of the cells with DS. In contrast with ASA and DS, pirprofen induced a marked increase in platelet protein synthesizing capacity. The drug decreased the platelet aggregation to a degree similar to that of ASA and DS. The release of platelet factors 3 and 4 and the level of beta-thromboglobulin following incubation with the drug remained unaltered.

X-ray microanalysis of the element content in the hearts of mice treated with digoxin.

The element content was detected by X-ray microanalysis in the hearts of mice treated with daily doses of 0.075 microgram digoxin for 12 days and compared with that of controls. Statistically significant differences were found for K and S, which were lower, and for P, which was higher following treatment with digoxin. In the sera of the treated mice Mg was slightly lower, whereas Ca and K levels were found to be elevated in comparison with those of nontreated animals. A possible explanation for these findings is discussed.

In vivo and in vitro effects of theophylline on the peripheral blood mononuclear cells from preterm infants.

The in vivo effect of aminophylline (theophylline ethylenediamine) on cAMP levels and the mitogenic response of peripheral blood mononuclear cells (PBMC) from preterm infants were investigated. Increased cAMP levels and reduced response of these cells to concanavalin A (Con A) were found in preterm newborns who received intravenous aminophylline. No inhibitory effect of the drug on phytohemagglutinin (PHA)-induced proliferation was observed. cAMP levels of PBMC derived from preterm infants were significantly lower than those of term newborns. The in vitro effect of theophylline on the mitogenic response of PBMC from adults, term and preterm infants was also compared. It was found that PBMC from adults were significantly more sensitive to the inhibitory effect of theophylline on Con A-induced proliferation than were PBMC from either term or preterm infants, whereas the effect of the drug on the mitogenic response to PHA was similar in the three groups. These data suggest differences either in the sensitivity to increased cAMP concentration between PBMC from adults and newborns or in their lymphocyte subpopulations.

Effect of verapamil on platelet surface ultrastructure and calcium content.

The effect of verapamil on the surface ultrastructure and calcium content of human platelets was studied by scanning electron microscopy and X-ray microanalysis. The results showed that the drug prevents platelet pseudopodia formation and causes a dose-dependent inhibition of platelet calcium concentration. The significance of these findings in the explanation of the inhibitory effect of verapamil on platelet aggregation is discussed.

Effect of pentoxifylline on E-rosette formation and on the mitogenic response of human mononuclear cells.

Pentoxifylline (Trental) has been shown to increase the intracellular cAMP concentration. In the present study we have examined the capacity of the drug to affect E-rosette formation by T lymphocytes. In addition, the mitogenic response of human lymphocytes to phytohemagglutinin (PHA) and concanavalin A (con A) was studied. The drug exerted a dose dependent inhibitory effect on E-rosette formation and on the proliferative response of lymphocytes to PHA and con A. It is suggested that this inhibitory effect is most probably due to the increased intracellular levels of cAMP induced by the drug.

Effect of pentoxifylline on the phagocytic activity, cAMP levels, and superoxide anion production by monocytes and polymorphonuclear cells.

The effect of pentoxifylline (Trental) on the phagocytic capacity, cAMP levels, and superoxide anion production of human peripheral blood monocytes and polymorphonuclears (PMNs) was studied. The drug inhibited the phagocytosis of latex particles by both monocytes and PMNs in a dose-dependent manner. In addition, superoxide anion production during the phagocytic process was also reduced following incubation of the cells with pentoxifylline. It is suggested that this inhibitory effect is due to the increased intracellular levels of cAMP induced by the drug.