Stability of aminoglycoside phosphotransferases, adenylyltransferases and acetyltransferases isolated from various sources was studied. The enzymes were characterized by different substrate profiles. They were stored at a temperature of -10 degrees C in the form of frozen solutions or at a temperature of 4 degrees C in the lyophilized form. It was shown that lyophilization markedly increased the stability of the enzymes inactivating aminoglycoside antibiotics. Aminoglycoside phosphotransferases and adenylyltransferases with streptomycin as substrate were less stable than aminoglycoside phosphotransferases with neomycin as substrate. Aminoglycoside acetyltransferases from Streptomyces fradiae 918 producing neomycin were least stable among the enzymes studied. Lyophilized enzymes as a possible stabilizer of ATP added to the preparations had no significant effect on their stability during storage.
The pharmacokinetics of bleomycetin, a new antitumor antibiotic prepared in the USSR, was studied microbiologically. The less the extent of the main tumor in the patients, the higher the antibiotic blood levels in them. This might be associated with the adsorption capacity of the tumor tissue. The dependence of the bleomycetin kinetics on the intensity of renal clearance was shown. The characteristics of the drug distribution in the blood after intravenous, intramuscular and intrapleural administration are presented.
Preparations of L-asparaginase made in the USSR, FRG and Japan were studied comparatively in 277 patients with acute lymphoblastic leukemia and lymphosarcomas. It was shown that the clinical characteristics of the preparation made in the USSR and the preparation (crasnitin) made in the FRG were identical. By the antileukemic action the preparation made in the USSR was superior to the preparation (leunase) made in Japan in the treatment of adult patients with such hemoblastosis forms. The effect of the three drugs in the treatment of children was analogous. The nature of the side effects of the three drugs was the same. However, their level was different. The allergenic effect of leunase on the patients was the most pronounced. L-Asparaginase made in the USSR and crasnitin are recommended for wide use in clinical practice.
The seasonal characteristics of the efficacy of vitamin E and sodium selenite in tetracycline affections of the liver were studied on 128 noninbred male albino rats. It was shown that in comparison to vitamin E sodium selenite more actively retarded activation of lipid peroxidation in the liver and activation of alanine aminotransferase and alkaline phosphatase in the blood serum in autumn and winter. A more pronounced inhibition of the increased levels of the dienic conjugates and alanine aminotransferase was observed in spring and summer and malonic dialdehyde and aspartate aminotransferase in summer by tocopherol acetate as compared to sodium selenite. The level of the thiol-disulfide equilibrium on the separate use of the drugs in spring and summer was higher than the control one. However, it did not reach the control level in autumn and winter. The combined use of sodium selenite and vitamin E prevented the toxic effect of tetracycline on the liver in autumn, spring and summer. Still, in the winter no such prevention was observed. The mechanisms of the seasonal differences in the tetracycline effect on the liver and the efficacy of the antioxidants in such affections are discussed.
The maximum dehydrogenase (oxidation-reduction) activity of the vegetative inoculum of S. aureofaciens is the criterion of its availability for transfer to the fermentation medium. The activity is determined by the rate of the methylen blue reduction and the growth characteristics of the seed culture. A method for estimation of the mycelium amount in the medium containing insoluble solid particles is described. The method is based on the capacity of the tetracycline-producing organism for decoloration of methylen blue.
The experiments on rabbits with intraocular infection provided determination of the optimal route and regimen of gentamicin administration in various dosage forms. Gentamicin sulfate made in the USSR was used. It was shown that during instillations of 0.3 per cent eye drops, gentamicin did not penetrate into the intraocular fluid. The ophthalmic drug films (ODF) containing 0.5 mg gentamicin per film provided better penetration of the antibiotic into the eye cavity in the concentrations in the ocular fluid active only against the most gentamicin sensitive microbial strains. Therefore, the use of the ODF containing gentamicin may be recommended for the treatment of intraocular infections caused by gentamicin sensitive organisms. When the antibiotic was administered subconjunctively in a dose of 20 mg, its therapeutic concentrations were mainly detectable in the anterior chamber fluid. Therefore, the use of this administration route was first of all rational in intraocular infections of the anterior part of the eye. The antibiotic should be used in such cases at least twice a day. The therapeutic concentrations of gentamicin active against the majority of the microbial strains were attained in the vitreous body only on intravitreal administration. The high therapeutic levels of gentamicin in the vitreous body after its injection in a dose of 0.4 mg were recorded for at least 4 days. Therefore, for the treatment of endophthalmitis the intravitreal route of gentamicin administration is of the greatest practical importance.
The antiinfluenza activity of roseofungin, a polyenic macrolide antibiotic was studied in vitro on surviving fragments of the chick embryo chorionallantoic membranes and in ovo on growing chick embryos. It was shown that the antibiotic activity against influenza A and B viruses was sufficiently high. The activity of roseofungin against influenza A virus did not differ from that of remantadin, the most active inhibitor of influenza virus reproduction. However, the activity of roseofungin against influenza B virus was an advantage of this antibiotic over remantadin, which had practically no effect on this virus type. A statistically significant protective effect of roseofungin (p less than 0.05) was shown on the animals with experimental influenza. The study on the antiviral activity of roseofungin against the DNA-containing variolovaccine virus revealed that it markedly inhibited the plague reduction. Roseofungin had a pronounced inhibitory effect on cell neoplastic transformation induced by the RNA-containing oncogenic virus of Rous sarcoma.
The use of benzylpenicillin and ampicillin in combination with sulfalen or sulfadimethoxine increased the levels of the penicillins and sulfalen in some organs and tissues of rats. This was accompanied by a rise in the concentration gradients of the drugs. It is concluded that the combined use of the penicillins and sulfanilamides determines their increased penetration from the blood into other organs and tissues of the host.
A procedure for highly purified cephalexin amidase of Xanthomonas was developed. It consists of preparation of a cell-free extract of the culture after cell disintegration, precipitation with ammonium sulfate, dissolution, concentration and elimination of ballast proteins, gel filtration on Sephadex G-25, sorption of ballast proteins on DEAE cellulose and chromatography on KM-cellulose. The enzyme yield is 45-55 per cent. The purity level is 80-90-fold.
The chemical and physicochemical characteristics of one of the two inactive components, i.e. the reduced product of alkaline inactivation (PAH-II) of ristomycin. A were studied. The components formed on the antibiotic incubation in mild alkaline media: 0.05 M NaOH, 37 degrees C, 1.5-2 hours. It was shown that the retroaldol cleavage of the C alpha-C beta bond of the phenol serine fragment of the trinuclear dideschlorvancomycinic acid G at the aglycone N-end was one of the causes of ristomycin A rapid inactivation under such conditions.
The effect of gentamicin sulfate on the rate of free radical oxidation of adrenalin was studied. Inhibition of the oxidation process at the final concentrations of gentamicin of 0.1-0.2 mg/ml was observed. The mechanism of gentamicin antiradical activity and its role in the cells are discussed.
Distribution of drug resistance in Salmonella isolated from different sources was studied over time. The strains of S. typhimurium characterized by more pronounced resistance to antibiotics were mainly isolated from infants. Circulation of such strains in animals was extremely rare. Some genetic markers of such pathogens were investigated.
Sixty-two patients with acute cholecystitis and 108 patients with chronic calculous cholecystitis were examined. High levels of contamination of the bile, gallbladder mucosa and gallstones were shown. E. coli, Staphylococcus and Streptococcus were most frequent among 20 species of aerobic and anaerobic bacteria. Preoperative sanation of the hepatoduodenal area with antibiotics did not result in complete elimination of the bacteria in the bile, gallbladder mucosa and gallstones. The use of nitrofurans and especially furazolidone and furagin in the preoperative period prevented the microbial growth in the specimens collected during the operations. The data of the study allow recommending the use of furazolidone and furagin for preoperative sanation of the biliferous tract.
The association and conformational structure of the molecule of erythromycin in solutions of CCl4, C2Cl4 and CHCl3 were studied by the IR spectra in the region of v OH and vC = O. The analysis of the concentration and temperature changes showed that the erythromycin association was accounted for by the hydrogen linkage of OH ... O = C to the ester group. In the monomer molecule of erythromycin, all hydroxyl groups participated in the intramolecular hydrogen linkage. Band 3513 cm-1 belonged to the OH group in the five-membered cycles of OH ... O. Components 3500, 3530 and 3560 cm-1 of the wide band vOH were assigned to the cycles with OH ... N and OH ... O linkages of a larger size. The association was due to a break in a part of the intramolecular hydrogen linkages. Addition of strong acceptors of proton-hexamethanol and trioctylphosphinoxide to the solution resulted in attenuation of these bands and appearance of a strong band vOH of the erythromycin-acceptor complexes. In the presence of monochloroacetic acid in the solution of CHCl3 stoichiometric protonization of erythromycin was observed. The total acid was in the form of anion (vaCO-2 1610 cm-1) up to a ratio of 1:1. The protonization proceeded according to the nitrogen atom since the antibiotic spectrum in the region of vC=O did not change. Propionic acid titrated erythromycin in methanol solution and in mixtures of water and methanol up to a ratio of 1:5 (v/v). However, in the solution of CHCl3 equilibrium between the neutral and ionized molecules of the acid was seen.
