[Aprotinin antiviral aerosol: study of the local irritating and allergenic action after inhalation]. / Antivirusnyi aérozol' aprotinina: izuchenie mestnorazdrazhaiushchego i allergiziruiushchego deistviia pri ingaliatsionnom vvedenii.

The aerosol of aprotinin, a natural low molecular weight polypeptide (m.w. about 160 kD) inhibiting a wide range of serine proteases may be used as an antiviral drug. The animal studies showed that it had no local irritating action on the mucosa. A long-term use of aprotinin in the form of a fine aerosol practically induced no allergenic side effects. The results of the study indicative of the absence of the allergic complications made it possible to recommend the aprotinin inhalations as a safe means in the treatment and prophylaxis of viral infections of the respiratory tract.

[The antiviral aerosol aprotinin. General effect on the body after inhalation administration]. / Antivirusnyi aérozol' aprotinina. Obshchee vozdeistvie na organizm pri ingaliatsionnom vvedenii.

A new medicine for the treatment of respiratory viral infections is described. It contains aprotinin, a natural inhibitor of proteases, and is used in the form of a fine aerosol for inhalation or intra-respiratory instillation. To estimate its innocuousness, the inhalation effect of the aerosol was studied on animals of two species. The experiments included examination of the functional state of the central nervous and cardiovascular systems, determination of the blood cell composition and biochemical blood count, morphological and histological investigation of the internal organs. The toxicological studies showed that aprotinin inhalation induced no adverse reactions which made it possible to recommend the aprotinin inhalation for the use in the treatment and prophylaxis of infections caused by a wide variety of respiratory viruses in humans.

[Study of general toxic and organotropic properties of clindamycin in long-term experiments]. / Izuchenie obshchetoksicheskikh i organotropnykh svoistv klindamitsina v khronicheskikh éksperimentakh.

The action of clindamycin monohydrate on the general state and weight rise, liver and kidney functions, peripheral blood count and pathomorphological state of the viscera was studied on rats in chronic experiments. Clindamycin was administered to laboratory animals orally in doses of 50, 100, 150 and 300 mg/kg. It was shown that some adverse reactions to the drug and in particular disorders in blood coagulation and morphological changes in the intestine did not depend on its dose and were due to duration of the drug use and probable development of dysbacteriosis. At the same time the disorders in the liver and kidney functions though transitory did depend, to a greater extent, on the dose and were evident after the antibiotic overdosage.

[Effect of rifampicin and doxycycline on leukocyte chemotaxis]. / Vliianie rifampitsina i doksitsiklina na khemotaksis leikotsitov.

It was shown experimentally that in a dose corresponding to the average therapeutic one for man rifampicin was able to stimulate in vivo directed migration of neutrophils to the inflammation foci in mice CBA. Doxycycline used in a dose corresponding to the average therapeutic one was able to activate neutrophils and to increase chemotaxis. Intraperitoneal administration of doxycycline to guinea pigs induced liberation of large counts of neutrophils with marked segmentation of the nuclei to the peritoneal cavity. The cells induced by doxycycline had a higher capacity for chemotaxis under agarose as compared to the control.

[Study of general toxic and organotropic properties of ampicillin combined with sulbactam]. / Izuchenie obshchetoksicheskikh i organotropnykh svoistv kombinatsii ampitsillina s sul'baktamom.

The effect of sulacillin, a combination of sulbactam and ampicillin (1:2), on the functions of the liver and kidneys, peripheral blood count, cardiovascular and central nervous systems was studied in acute and chronic experiments on animals of various species. The allergenic and local irritating properties of the combination were also studied. It was shown that the combination was low toxic and the interaction of sulbactam and ampicillin by the lethal effect was additive. When the combination was administered intravenously to mice, its LD50 amounted to 6 g/kg. In chronic experiments on rats parenterally given the combination in doses equivalent to the therapeutic ones there were no changes in the examined systems and organs. When used in the doses exceeding the therapeutic ones, sulacillin used during long periods induced a transitory elevation of blood levels of transaminases and alkaline phosphatases, an increase in the relative weight of the liver and kidneys, elongation the typhlon and an increase in glycogen levels in the hepatocytes without morphological changes. The combination had no significant effect of sulacillin and the painful injections alleviated by local anesthesia were recorded. The allergenic properties of the combination were moderate and did not differ from those of ampicillin. The data indicate that the combined sulacillin preparation greatly resembles its foreign analogue.

[Biologic activity and tolerance of a preparation of polyunsaturated fatty acids, obtained by a microbiological route ["biopolyene"]]. / Biologicheskaia aktivnost' i perenosimost' preparata polinenasyshchennykh zhirnykh kislot, poluchaemykh mikrobiologicheskim putem ["biopoliena"].

Biopolyene is a mixture of ethyl ethers of polyunsaturated fatty acids isolated from biomass of Entomophthora virulenta, a mycelial fungus. Its acute and chronic toxicity was studied on rats and guinea pigs. After oral administration of the preparation in single doses exceeding 50 g/kg there were no disorders in the general state of the rats. In chronic experiments with oral biopolyene in doses of 100 and 500 mg/kg and its local application to the intact skin of the animals in a dose of 1 g/kg there were no significant changes in the functional state of the liver and kidneys as well as the peripheral blood count. Insignificant changes in the serum levels of liver enzymes and coagulation were transient. The preparation showed no allergenic or immunomodulating effects. It had neither embryotoxic, teratogenic nor mutagenic action.

[Experimental study of protease C--proteolytic enzyme of microbial origin]. / Eksperimental'noe izuchenie proteazy C--proteoliticheskogo fermenta mikrobnogo proiskhozhdeniia.

The specific activity of protease C, a proteolytic enzyme isolated from Acremonium chrysogenum was studied under experimental conditions. Protease C was shown to lyse necrotic biological substrates (dry crusts of burn wounds) and blood clots. By the nature of the effect protease C was analogous to terrilytin and by the level of the effect it was superior in some experiments. Protease C was low toxic and had no mutagenic action.

[Tolerance of gentacycol--a local dosage form of gentamicin based on collagen--animal experiments]. / Perenosimost' gentatsikola--mestnoi lekarstvennoi formy gentamitsina na osnove kollagena--v éksperimentakh na zhivotnykh.

Gentacycol is a local dosage form of gentamicin based on collagen for implantation to wounds in treatment of patients with infections of soft tissues and prevention of contamination of open injuries of the bones and soft tissues. General toxic and organotropic properties of gentacycol were studied on animals with subcutaneous implantation of the dosage form in doses equivalent to the therapeutic dose for man and exceeding it 2-fold. The study showed that the dosage form had no unfavourable side effects on the animal general state, hearing, the functional state of the liver and kidneys and the peripheral blood. In the doses tested gentacycol did not influence the indices of the cardiovascular system and neuromuscular conduction. Morphological examination of the skin and hypodermic tissues in the implantation site revealed no damaging action of the dosage form on the surrounding tissues.

[Experimental study of a novel formulation for local application based on gentamicin, erythromycin and protease C]. / Eksperimental'noe issledovanie novogo lekarstvennogo preparata dlia mestnogo primeneniia na osnove gentamitsina, éritromitsina i proteazy C.

A novel formulation for local application based on an enzyme of microbial origin, C protease, and two antibiotics, gentamicin and erythromycin, was studied on various experimental models in rats with respect to its effect on necrotic tissues and recovery of the skin and hypodermic tissue defects due to wounds. It was found that even within the first days of the application the formulation induced lysis of the primary crust, lowered exudation and promoted debridement, reduced the wound size and completely closed it. By its effect the formulation was similar to iruxol. In chronic experiments on animals with long-term application of the formulation to the skin and wound surfaces it showed no unfavourable general toxic or organotropic properties. The local irritating action was insignificant.

[General toxic and organotropic properties of cefotaxime in acute and chronic experiments]. / Izuchenie obshchetoksicheskikh i organotropnykh svoistv tsefotaksima v ostrykh i khronicheskikh éksperimentakh.

The action of cefotaxime on the functions of the liver and kidneys, the peripheral blood count, growth and development of young animals, blood circulation, respiration and the central nervous system was studied in acute and chronic experiments on mice and rats. Allergenic, immunomodulating, embryotoxic and teratogenic properties of the antibiotic were also studied. Cefotaxime was shown to be low toxic. After intravenous administration to mice, its LD50 amounted to 7000 (6295-7805) mg/kg. In the chronic experiments on rats with intramuscular and intravenous administration of the antibiotic in doses equivalent by the body surface to the course doses for humans there were no significant shifts in the function of the liver and kidneys, the count of the blood formed elements and the histologic pattern of the viscera. In the therapeutic doses the antibiotic had no action on hemopoiesis, respiration and the central nervous system. The allergenic properties of cefotaxime were slightly pronounced and similar to those of klaforan. The antibiotic had no action on the host immunity and showed no embryotoxic and teratogenic properties. After intravenous and intramuscular administration, cefotaxime had a slight irritating action on the tissues which was similar to that of klaforan.

[Mechanism of hypotension induced by rifampicin during intravenous administration]. / K mekhanizmu gipotenii, vyzyvaemoi rifampitsinom pri vnutrivennom vvedenii.

In vivo and in vitro experiments showed that the mechanism of hypotension induced by rifampicin was not associated with its effect on peripheral m- and n-cholinoreactive and adrenoreactive systems. It was due to the direct action of the drug on the vessel muscular wall and its mediated effect on the histaminergic systems participating in vascular tension control.

[Action of the antitumor antibiotic aclarubicin on the blood system and bone marrow hematopoiesis in an experiment]. / Deistvie protivoopukholevogo antibiotika aklarubitsina na sistemu krovi i kostnomozgovoe krovetvorenie v éksperimente.

The effect of various doses of antitumor antibiotic aclarubicin on the peripheral blood system and medullary hemopoiesis was studied on Wistar rats. It was shown that intraperitoneal administration of the drug in doses of 0.08, 0.33 and 1.2 mg/kg daily for 6 months did not induce any significant changes in the blood count of the animals. The dose of 1.2 mg/kg which is almost 2.5 times higher than the maximum course dose of aclarubicin for patients induced a decrease in the hemoglobin count recorded within the whole observation period. A single administration of aclarubicin in LD50 equal to 17.4 mg/kg resulted in marked suppression of hemopoiesis. The drug had the most prolonged suppressive effect on the bone marrow myeloid body. Depression of erythropoiesis was short-term.

[General toxic and organotropic properties of azlocillin in acute and chronic experiments]. / Izuchenie obshchetoksicheskikh i organotropnykh svoistv azlotsillina v ostrom i khronicheskom éksperimente.

The general toxic and organotropic properties of azlocillin were studied in acute and chronic experiments with various animal species. By the body surface area the doses of azlocillin were equivalent to the drug average and maximum course doses for humans. The aim of the study was to determine the drug dose inducing certain side effects. It was found that only in a dose equivalent to the maximum course dose for humans i. e. 300 g the drug induced a transient increase in the blood levels of aspartate aminotransferase and alkaline phosphatase and some increase in the coagulation time. The allergenic properties of the drug were slightly pronounced. Within the tested doses azlocillin did not affect the peripheral blood indices and showed no immunomodulating embryotoxic, teratogenic or mutagenic effect. The experimental data indicated that the range between the drug therapeutic course doses and the doses inducing certain side effects was significant. This is evidence of a sufficiently high level of azlocillin safety.

[Experimental study of the pharmacological properties of amikacin]. / Izuchenie farmakologicheskikh svoistv amikatsina v éksperimente.

The general toxic and organotropic properties of amikacin were studied in acute and chronic experiments. The antibiotic was administered to the experimental animals in the doses equivalent to the therapeutic ones for humans or exceeding them 2-3 times. No unfavourable effect of amikacin in the above doses on hearing was observed. A certain increase in the level of urea nitrogen in the blood serum and leukopenia were registered only after administration of the highest drug dose exceeding 2 times the equivalent treatment dose of amikacin for humans (15 g). After the use of this dose separate microfocal necrotic lesions were detected morphologically in the proximal tubules of the kidneys. The lesions were of a transitory nature. It is concluded that amikacin has a wide range of therapeutic doses and the level of its safety is rather high.

[Action of reumycin on the blood system in an experiment]. / Deistvie reumitsina na sistemu krovi v éksperimente.

The effect of reumycin, an antitumor antibiotic on the peripheral circulatory system and bone marrow was studied on albino rats. The drug was injected intraperitoneally in a dose of 25 mg/kg daily for 30 days. It was shown that reumycin had a comparatively low toxic effect on the peripheral circulatory system and hemopoiesis. It induced the signs of transitory anemia and did not suppress the regenerative capacity of the bone marrow. After the drug repeated use there was an increase in the platelet count and in the rate of blood coagulation. These signs vanished a month after the end of the treatment course.

[Comparative study of sisomicin and gentamycin action on the cells in a tissue culture]. / Sravnitel'noe izuchenie deistviia sizomitsina i gentamitsina na kletki v kul'ture tkani.

The cytostatic effect of sisomicin and gentamicin, antibiotics from the group of aminoglycosides was studied comparatively with respect to three types of tripsinized cells of chick embryo (cells of the kidneys, liver and fibroblasts). It was found that epithelial cells and in particular kidney cells were most sensitive to the above antibiotics as compared to fibroblasts. It was also shown that gentamicin had a lower cytostatic effect on the embryonal cells of the kidneys, liver and fibroblasts as compared to sisomicin.

[Placental permeability for rifampicin]. / O pronitsaemosti platsenty dlia rifampitsina.

Albino rats were exposed to rifampicin inhalations for a prolonged period of time (during gravidity). It was found that the antibiotic penetrated through the placental barrier and its levels in the fetus were proportional to its content in the air inhaled. At later gravidity periods rafampicin absorption in albino rats increased and in parallel its levels in the ovum also increased. The exposure of albino rats to rifampicin inhalations during the whole period of their gravidity in concentrations lower than the Limac (the limit of the acute effect with respect to the general toxic parameters) did not affect the structure of the placenta and its permeability by the antibiotic.

[Kinetic patterns in the growth of transplantable mouse tumor RShM-1]. / Kineticheskie zakonomernosti rosta perevivaemoi opukholi myshei RShM-1

Under study was the kinetics of growth of cervical cancer (CCM-1) transplanted on mice CBA, also the mitotic cycle and diurnal activity of tumor cells division. The tumor growth can well be described with the Hompertz equation, the constants of acceleration and retardation being equal to 0.34 day-1 and 0.004 day-1 accordingly. A linear dependence between the size, weight and number of CCM-1 celos is shown. In the tumor under study a persistant diurnal rhythm of the cell division was found with the maximum at 7 and 19 hours and the minimum at 13. The basis parameters of the mitotic cycle of tumor cells were determined: Tc=17.8 hr., G2 approximately 40 min.; S=9 hr., M approximately 24 min., G1 approximately 18.4 hr. The time of tumor doubling was 48.7 hr. The cell loss factor is as much as 42.1 per cent.