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R F Vidal

Publications and source records attributed to R F Vidal.

12 recordsLinked to original sources

Anthraquinone-induced cell injury: acute toxicity of carminomycin, epirubicin, idarubicin and mitoxantrone in isolated cardiomyocytes.

Acute toxic effects of the antineoplastic anthraquinones carminomycin, epirubicin, idarubicin and mitoxantrone were studied in primary cultures of cardiomyocytes, which were isolated from adult rats. Both time- and concentration-dependent changes of cell structure and viability (trypan blue exclusion) following incubation of myocytes with subclinical, clinical and toxic concentrations of the anthraquinones were examined by light microscopy. The area under the decay curve of viable and rod-shaped myocytes was used to express cytotoxicity of the drugs. Mitoxantrone was found to reduce cell viability and number of rod-shaped cells to the greatest extent, followed by carminomycin, idarubicin and epirubicin. A significantly lower accumulation in cardiomyocytes was obtained with epirubicin and idarubicin compared with carminomycin. An inhibitory effect on oxygen consumption by the cells occurred already at 0.1 microM with epirubicin, whereas inhibition caused by other anthraquinones was less pronounced. Our data indicate a weak association of net accumulation and the toxicity parameter IC50 for carminomycin and idarubicin. In contrast to these results, a more significant correlation of cytotoxicity and anthraquinone lipophilicity was found, which suggests that the lipophilic character of a particular anthraquinone may be an important factor in drug-induced acute cardiotoxicity.

Animals↗

Doxorubicin- and daunorubicin-induced energy deprivation and nucleotide degradation in isolated cardiomyocytes.

Cytotoxic mechanisms of the antitumor agents daunorubicin and doxorubicin were elucidated in isolated cardiomyocytes from adult rats. Incubation with daunorubicin resulted in a concentration-dependent loss of cell viability and changes of the cell structure. Only the highest concentration of doxorubicin (1 mM) caused similar effects. Doxorubicin was found to stimulate oxygen consumption by cardiomyocytes (about 20%), while the opposite effect was observed after daunorubicin treatment. A rapid decrease of the mitochondrial ATP content (more than 40%) and elevation of the cytosolic ADP level (doxorubicin 2-fold and daunorubicin 6-fold) was followed by increased release of adenosine and inosine to the surrounding medium. When myocytes were exposed to an anthracycline concentration lower than plasma levels measured clinically (0.15 microM), doxorubicin and daunorubicin significantly decreased the intracellular ADP and NAD levels. Isolated cardiomyocytes were found to be able to form daunorubicinol from daunorubicin. In contrast, no conversion of doxorubicin was detected in our experiments. In conclusion, our data demonstrate that decreased ATP production and increased nucleoside formation are major events in the toxicity induced by daunorubicin and doxorubicin in isolated cardiomyocytes. The results also suggest that the toxic effects may be caused by separate mechanisms.

Adenosine Diphosphate↗

Hydroperoxide-induced nucleotide degradation and adenosine formation in isolated rat cardiomyocytes.

The effect of tert-butyl hydroperoxide (tBH) on the nucleotide level in isolated cardiomyocytes from adult rats was examined. Incubation of myocytes with the hydroperoxide resulted in loss of both ATP and NAD from mitochondria and cytosol. In contrast, only the cytosolic level of NADP was increased. The effect on myocyte content of ADP and AMP was less pronounced. A significant increase in formation and release of adenosine also occurred in tBH-exposed cells. Treatment of cardiomyocytes with tBH resulted in a progressive decline of rod-shaped and viable cells, which was accompanied by an increase in numbers of hypercontracted and round myocytes in the incubation mixture. Electron microscopic examination showed an intense contraction of the cells. In summary our results demonstrate that plasma membrane damage and hypercontraction are early manifestations of tBH-induced injury to isolated cardiomyocytes. The depletion of ATP and formation of adenosine also suggest that degradation of adenine nucleotides may contribute to the cytotoxicity caused by tBH. Possible mechanisms involved in the ATP depletion are discussed.

Adenine Nucleotides↗

[Rabbit experimental glaucoma--preliminary study (author's transl)].

Induced high intraocular pressure, lasting more than one hour, is described in the rabbit. We inject simultaneously inside aqueous humor Epsilon Amino Caproic Acid 5 mg and Thrombin 20 U.S.N.I.H. units. To avoid leakage of aqueous humor we make the injection though a nou-perforating corneal preplaced loep and sight the suture to close the track when injection needle is taken out. We assume that high intraocular pressure is induced by 1% Adrenaline, 2% Pilocarpine and 1% Guanethidine solutions dropped in the eye each 5 mn, beginning 15 mn before anterior chamber injection and lasting during all the experiment. We point out this fact as a proof of the suitability of this method.

Aminocaproates↗

[Experimental retinal vascular photocoagulation with the argon laser. Optic microscopic study of the results in rabbits and humans].

Argon laser vascular retinal photocoagulation's experimental study on rabbit point out hemorrage risk when using 1500 mw, 0,05 sec, 200 microns beam. If 800 mw 0,05 sec, 200 microns beam is selected white cell migration comes at 48 hours inside and outside the photcoagulated vessel. On human one can success intermaculopapillar photocoagulations without injurying intern retinal layers (we use 300 mw, 0,05 sec, 200 microns beam). At 650 mw, 0,05 sec, 200 microns perivascular retinal injury is considerable, but at 24th hour on artery there is no evidence of obliteration possibility.

Animals↗

[Experimental phaco-emulsification in the rabbit. Induced corneal endothelial lesions, regeneration at 24 hours (author's transl)].

The purpose of this study was to evaluate action of the Shock phacofragmentor's tip vibrations; this study was done in rabbit corneal endothelium: 1--Tip in the anterior chamber close to the cornea and iterative entrances by the incision; 2--In order to avoid some endothelial injuries, it appears necessary to introduce the instrument only once and also use the vibrations only inside the nucleus. Then the lens materials can be removed by irrigation and or aspiration.

Animals↗

[Experimental keratoplasty after sensitization by a bacterial antigen (Streptococcus A group)].

Experimental (rabbit) penetrating keratoplasties with donor tissue sensitized to a bacterial antigen (Streptococcus Group A) were placed in normal rabbits and animals sensitized to the same antigen. Severe graft reactions developed two months after grafting in sensitized rabbits while no reaction occurred in controls. It is possible that homograft reactions can be triggered and super-imposed to the immuno-allergice reaction to the foreign antigen present in host and donor.

Animals↗