[Complications in preparations for prosthesis for children with defects of the extremities by Italian plastic surgery and surgery using Filatov's flap]. / Oslozhneniia pri podgotovke k protezirovaniiu detei s defektami konechnostei ital'skoi plastikoi i plastikoi filatovskim steblem.

The authors make an analysis of results of skin plasty in 67 children. The amount of complications was shown to be considerably high but the operations are thought to be justified after performing medico-training prosthezing.

[Study of the toxicity of carminomycin 13-cyclohexylidenhydrazone]. / Izuchenie toksichnosti 13-tsiklogeksilidengidrazona karminomitsina.

The systemic effect and toxicity of carminomycin 13-cyclohexylidenhydrazone (CCH) were studied on noninbred albino mice in comparison to carminomycin. The preparation was administered intravenously and orally. It was shown that CCH was 1.3 or 2.5 times less toxic than carminomycin on its intravenous or oral administration, respectively. The cumulative properties of CCH and carminomycin on their intravenous administration were practically equal. On oral administration of CCH the level of its cumulation in mice was higher than that of carminomycin. By its nature the effect of the preparations on hemopoiesis of the mice was the same. CCH had a low cardiotoxic effect.

[Toxicity, pharmacokinetics and pharmacodynamics of the Soviet bleomycin, bleomycetin, in a single administration to laboratory animals]. / Izuchenie toksichnosti, farmaokinetiki i farmakodinamiki otechestvennogo bleomitsina--bleomitsetina pri odnokratnom vvedeni laboratornym zhivotnym.

Toxicity of bleomycetin (bleomycin A2) administered intravenously, intraperitoneally, subcutaneously or intramusculary in a single dose to animals was almost identical. On its oral administration bleomycetin was 10--14 times less toxic than on its parenteral use. Rats were somewhat less sensitive to bleomycetin than mice. Bleomycetin had no significant effect on the level of the arterial pressure, respiration, ECG characteristics and elements of the vegetative nervous system in narcotized cats. After a single intravenous or subcutaneous administration to rabbits bleomycetin was detectable in the blood for 4--5 hours. The highest bleomycetin levels were registered in the skin, kidneys and lungs. Bleomycetin was mainly excreted with the urine.

[Toxicity of tobramycin in single and multiple administrations to laboratory animals]. / Izuchenie toksichnosti tobramitsina pri odnokratnom i mnogokratnom vvedenii laboratornym zhivotnym.

The LD50 of tobramycin sulphate administered intravenously, intraperitoneally, subcutaneously and orally to albino mice was 77 (73--82), 262 (234--294), 560 (500--627) and greater than 10500 mg/kg respectively. With an increase in the rate of intravenous administration tobramycin toxicity increased. When tobramycin sulphate was administered subcutaneously daily in multiple doses equivalent to the daily therapeutic doses from humans (calculated for the body surface) and in the doses 2--3 times higher than the above therapeutic ones, the function of the kidneys, liver and the Preier's reflex did not significantly change. When the doses were 8--10 times higher than the therapeutic ones, an increase in the urea level in the blood serum, disappearance and a decrease in the Preier's reflex were observed. The impairment of the kidney function was accompanied by degenerative changes in the convoluted tubules of the kidneys, ischemia of the renal glomeruli and appearance of protein secretion in their capsule cavities. The picture of the peripheral blood did not suffer significant changes. The studies on the acute and chronic toxicity of tobramycin sulphate prepared at the Institute of New Antibiotics showed that the drug did not differ from the import tobramycin samples.

[Effect of the multiple peroral administration of carminomycin on the body of animals]. / Vliianie karminomitsina na organizm zhivotnykh pri mnogokratnom peroral'nom vvedenii.

Toxicity of carminomycin used orally for many times was mainly evident from suppression of blood formation, the level of the suppression being dependent on the antibiotic dose. Carminomycin had a low suppressing effect on the white blood in rats. At low doses even moderate leucocytosis was observed. The indices of the functional state of the liver, kidneys, sugar blood levels, content of glycogen and fat in the liver, relative mass of the rat organs after repeated oral administrations of karminomycin to the animals remained mainly unchanged. A change in wave T on the ECG of the dogs treated with high doses of the antibiotic was registered. Histological examination of the organs and tissues of the animals killed after repeated oral administrations of carminomycin revealed pathological changes only in the spleen and thin intestine. Such changes were not more pronounced than those after repeated intravenous administration of the equivalent doses of the antibiotic (by the effect on the blood formation). This allowed the author to recommend the oral administration route for carminomycin trials in clinics.

[Acute toxicity of carminomycin administered perorally to laboratory animals]. / Izuchenie ostroi toksichnosti karminomitsina pri peroral'nom vvedenii laboratornym zhivotnym.

Rather high species sensitivity to carminomycin was found in the experiment with albino mice, rats, guinea pigs, rabbits and dogs. The highest difference in the antibiotic toxicity for various species of the laboratory animals was shown on oral administration of the drug which was due to the differences in the antibiotic absorption from the gastro-intestinal tract. On single oral administration to the dogs in toxic or lethal doses the antibiotic suppressed the blood formation up to aplasia of the bone marrow. The equitoxic doses of carminomycin on its single oral and intravenous administration differed approximately by 3 times. Carminomycin had no effect on the smooth muscles of the isolated rabbit ear vessels and cat intestine in situ. The antibiotic had an irritating effect on the rabbit eye mucosa. Carminomycin had no skin-irritating effect.

[Comparative study of the cardiotoxicity of the anthracycline antibiotics, rubomycin, carminomycin and dihydrocarminomycin, in experiments on white mice]. / Sravnitel'noe izuchenie kardiotoksichnosti antratsiklinovykh antibiotikov rubmoitasina, karminomitsina i digidrokarminomitsina v opytakh na belykh myshakh.

The experiments on albino mice treated with rubomycin, carminomycin or dihydrocarminomycin on its 5-fold intravenous administration in doses equal to similar portions of LD50 of the respective antibiotic on its use in a single dose showed that all the 3 antibiotics induced changes in the myocardium close by their character. The heart affections were evident from swelling of separate muscle fibers, degeneration of the myofibrils, homogenization, vacuolization and resorption of the sarcoplasma, pathological changes in the nuclei, atrophy of some muscle fibers. Rubomycin had the highest cardiotoxic effect. Then followed dihydrocarminomycin and carminomycin. All the antibiotics studied in the experiments with mice had mainly an inhibitory effect on the lymphoid hemopoiesis. The effect of carminomycin was the highest. The animal death during the injections and immediately after administrations of the antibiotics must be due to their suppressing effect on hemopoiesis. The deaths at more remoted periods must be due to the cardiotoxic effect of the antibiotics.

[Comparative study of the cardiotoxicity of the anthracycline antibiotics, carminomycin and adriamycin, in white mice]. / Sravnitel'noe izuchenie kardiotoksichnosti antratsiklinovykh antibiotikov karminomitsina i adriamitsina na belykh myshakh

The cardiotoxic effect of karminomycin and adriamycin administered intravenously for 5 times in equitoxic doses constituting equal portions of LD50 of the respective antibiotic on its single intravenous administration was studied on albino mice. Histological examination of the heart showed that almost identical damages of the myocardium occured after administration of karminomycin and adriamycin in doses of 0.45 of LD50 (1.5 mg/kg) and 0.3 of LD50 (6.3 mg/kg) respectively. The character of the damages due to the antibiotics was close, the most significant changes were observed when the animals were sacrificed 1 month after the last administration of the drug. The histological method is of value in estimation of the cardiotoxic effect of the drugs, using mice as the model suitable for the investigation. Adriamycin had more pronounced cumulative properties as compared to karminomycin: suppression of the weight gain in the mice and their death rate were higher with the use of adriamycin.

[Toxicity and pharmacological properties of carminomycin complex components]. / Toksichnost' i farmkologicheskie svoistva komponentov karminomitsinovogo kompleksa

Acute toxicity of the components of the carminomycin complex after intravenous administration to albino mice increased as follows. I less than II less than III. Component II induced a decrease in all the indices of the bone marrow and peripheral blood of the animals. It was most pronounced in dogs. The dogs died after administration of component II in the lethal doses as a result of the bone marrow aplasia. The indices of the functional state of the liver and kidneys in the animals after administration of components I and II changed slightly. Component III administered repeatedly to rabbits even in low doses induced significant impairments in the function of the liver and kidneys. Component II differed from component I by more pronounced cardiotoxicity. On the basis of the experimental data and the results published earlier component I is recommended for clinical trials as the least toxic one.