[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.

[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.

[Substantiation of hygienic standard of lincomycin in the air of the work area]. / Obosnovanie gigienicheskogo standarta linkomitsina v vozdukhe rabochei zony.

The main parameters of lincomycin toxicometry were studied in animals. It was shown that the compound was low toxic after its oral or intraperitoneal administration in single doses, had no local irritant and skin resorptive effects and did not accumulate. The allergenic properties were slightly pronounced. The intoxication picture after a single inhalation was characterized by renal dysfunction, erythropenia, neutrophilia, lymphopenia and impairment of the normal intestinal microflora. The zone of the specific antimicrobial effect was equal to 8. On chronic inhalation, the signs of the specific antimicrobial effect were of the paramount importance: Limch am was equal to 4.7 mg/m3 and Limch exceeded 18.3 mg/m3. In the concentrations used, the substance had no embryotoxic and gonadotropic effects. The level of 0.5 mg/m3 (for Hazard Class 2) was recommended and approved as the maximum allowable concentration.

[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.

[Interrelations in the changes in the pharmacokinetics and nephrotoxic effect of sisomycin as affected by cefazolin]. / Vzaimosviaz' izmenenii v farmakokinetike i nefrotoksicheskom éffekte sizomitsina pod vliianiem tsefazolina.

The action of cefazolin on the pharmacokinetics and nephrotoxic effect of sisomicin was studied on Wistar rats. Sisomicin in doses of 12.5 and 25 mg/kg alone or in combination with cefazolin in doses of 90 and 360 mg/kg was administered intramuscularly to the animals daily for 16 days. It was shown that in both the doses cefazolin had no noticeable action on the level of the functional and morphological changes in the kidneys. Consequently, there were no significant changes in the levels of sisomicin in serum and the site of the nephrotoxic effect (cortical layer of the kidneys) and in the half-life of the aminoglycoside in the kidney cortical layer under the action of cefazolin. At the same time there was observed a marked individual variability of the levels of urea nitrogen and sisomicin in serum of the rats treated with the aminoglycoside alone or in combination with cefazolin. Analysis of the dependence of the nephrotoxic effect on concentration of sisomicin in serum after its use alone or in combination with cefazolin revealed that the changes in the individual intensity of the effect in all the cases were mainly induced by the changes in the sisomicin blood levels. Therefore, control of the blood levels of the aminoglycoside should provide prevention of the development of its nephrotoxic effect not only in monotherapy but also in the use of aminoglycosides in combination with cefazolin.

[Decrease of sisomicin nephrotoxicity as affected by cephalothin: pharmacokinetic evaluation]. / Oslablenie nefrotoksichnosti sizomitsina pod vliianiem tsefalotina: popytka farmakokineticheskogo ob'iasneniia.

The effect of cephalothin on the nephrotoxicity and pharmacokinetics of sisomicin was studied on Wistar rats. Sisomicin was injected intramuscularly in doses of 12.5 and 25 mg/kg alone or in combination with cephalothin in a dose of 360 mg/kg once a day for 16 days. It was shown that the combined use of sisomicin and cephalothin resulted in less pronounced functional and morphological changes in the kidneys as compared to the use of sisomicin alone. The decrease in the nephrotoxic effect was accompanied by a decrease in the sisomicin concentration in the blood serum and the site of the nephrotoxic effect (the kidney cortical layer) and the period of the aminoglycoside half-life in the kidney cortical layer under the action of cephalothin. The analysis of the relation between the nephrotoxic effect and the concentration of sisomicin in the kidney cortical layer and blood serum demonstrates that the nephrotoxicity of the sisomicin combination with cephalothin is mainly due to a decrease in the aminoglycoside concentration in the zone of the nephrotoxic effect.

[Effectiveness of the rapid intravenous administration of rifampicin and isoniazid and of the intramuscular administration of streptomycin in disseminated destructive pulmonary tuberculosis in dogs]. / Effektivnost' ékspressnogo vnutrivennogo vvedeniia rifampitsina, izoniazida i vnutrimyshechnogo vvedeniia streptomitsina pri rasprostranennom destruktivnom tuberkuleze legkikh u sobak.

Soluble rifampicin and isoniazid injected rapidly by the intravenous route and streptomycin injected intramuscularly to dogs with disseminated destructive tuberculosis of the lungs provided sterilization of the organs with respect to M. tuberculosis for the period of their use for 2 months. This was confirmed microbiologically. The treatment resulted in resolution of the dissemination foci in the organs and stimulation of immunomorphological and connective tissue reactions in the lungs until the foci cicatrized. The shifts in liver function (bilirubin, ALT and AST) and coagulograms during the treatment were temporary and came to normal by the end of the treatment. The organotropic effect of soluble rifampicin in combination with isoniazid injected rapidly by the intravenous route and streptomycin injected intramuscularly was not observed during the treatment of the dogs with disseminated destructive tuberculosis of the lungs. Rapid intravenous injection of rifampicin in combination with other antimicrobial drugs will provide a significant decrease in the periods of chemotherapy of patients with disseminated destructive tuberculosis of the lungs.

[Experimental study of the action of the antitumor antibiotic reumycin on the macroorganism]. / Eksperimental'noe izuchenie deistviia protivoopukholevogo antibiotika reumitsina na makroorganizm

The side effect of reumycin, an antitumor antibiotic was studied experimentally. The average lethal dose for mice and rats on intravenous administration of the drug was 45.5 and 42.2 mg/kg respectively. When reumycin was administered to rats and dogs for prolong periods of time, an increase in the levels of total protein, urea nitrogen and inorganic phosphorus in the blood was observed, while the levels of hemoglobin and thrombocyte counts decreased, the process of the blood coagulation being slower. The changes in the ECG were similar to those observed in the myocardium dystrophy. The morphological changes in the organs were characterized by perivascular edema, swelling of the vessel walls and edema of the interstitial tissues.