Effect of antibiotics on indices of immunologic reactivity in mice

The effect of ristomycin, chloramphenicol, kanamycin, benzylpenicillin, streptomycin, and cephaloridine on the indices of cellular and humoral immunity was studied comparatively on intact animals and on animals with secondary immune deficiency. The study of the antibiotic effect on the count of rosette-forming lymphocytes (RFL) and the total count of lymphocytes showed that all the antibiotics except streptomycin induced a significant decrease in the count of RFL. The most active was kanamycin. It lowered the count of RFL 5-fold as compared to the control. The total count of lymphocytes was lowered after administration of ristomycin, chloramphenicol and kanamycin. In the animals with immune deficiency induced by cyclophosphamide benzylpenicillin potentiated the inhibitory effect of cyclophosphamide on the weight of the lymphoid organs, while streptomycin lowered the effect of cyclophosphamide. No such effect was observed with the use of the other antibiotics. The data indicated the necessity of taking into account the effect of various antibiotics on the immune system, especially under conditions of immune deficiency.     

Effect of hydroacridine derivatives on the sensitivity of polyresistant strains of Staphylococcus aureus and Escherichia coli to antibiotics]

Sensitivity of 4 clinical strains of Staph. aureus and E. coli to 13 hydroacridine derivatives and their combinations with antibiotics, such as benzylpenicillin, ampicillin, semi-synthetic penicillins, streptomycin, chloramphenicol, tetracycline, chlortetracycline, monomycin, oleandomycin and erythromycin was studied. The highest bacteriostatic effect was observed on the use of perhydroactidine derivatives with benzylpenicillin or ampicillin with respect to polyresistant penicillinase-producing strains of Staph. aureus, resistance of which to these antibiotics was decreased 250--1000 times. Under the effect of the above compounds the staphylococcal resistance to chloramphenicol, tetracycline, chlortetracycline, oleandomycine and erythromycin decreased 2--66 times. The combinations of hydroacridine with the antibiotics, except 10-amino-trans-syn-trans-perhydroacridine had no effect on the resistance of the E. coli strains. The results of the combined effect of the above substances were associated with their chemical nature, the bacterial type and possibly the character of the strain resistance.     

Parameters affecting the in vitro maturation of human monocytes to macrophages

In vitro maturation of human monocytes to macrophages was characterized by morphological criteria, cell size and lysosomal enzymes activity. Purified populations of monocytes were maintained in culture at either adherent or nonadherent conditions and their maturation to macrophages was observed in both cases. The addition of external factors such as hydrocortisone and vitamin D3 inhibited monocyte maturation. In the absence of external factors, nonadherent monocytes were inhibited in their maturation for up to 10 days when plated at crowded cell concentrations. In addition, the presence of human serum in the culture media had a higher inhibitory activity than similar concentrations of fetal calf serum. Supernates from crowded macrophages were also inhibitory for monocyte maturation. We suggest the possibility that cell crowding, as well as soluble factors found in the serum and probably secreted by macrophages, participate in the regulation of monocyte development by inhibiting their maturation. Once released from this inhibitory signal or environment, the monocytes mature to macrophages.     

Resistance of the strain Streptomyces hygroscopicus 155 to autogenous and other antibiotics]

Streptomyces hygroscopicus 155, a strain producing pandavir (nigericin) and azalomycin, was studied with respect to resistance to its own and some other antibiotics i.e. tetracycline, gentamicin, streptomycin, erythromycin, tylosin, thiostreptone, benzylpenicillin, monensin and salinomycin. An inactive variant of the culture was used in the control.     

The sensitivity to 12 antibiotics of 125 strains of Streptococcus group B isolated in a maternity home

Sensitivity of 125 strains of group B streptococci isolated from newborns, their mothers and personnel in a maternity home was studied with respect to 12 antibiotics: benzylpenicillin, ampicillin, methicillin, cephalotin, erythromycin, lincomycin, levomycetin (chloramphenicol), oxacillin, tetracycline, streptomycin, gentamicin and ristomycin. The method of serial dilutions in a solid medium was applied. All the strains were sensitive to ristomycin and erythromycin. The predominating number of the strains were sensitive to lincomycin, levomycetin and the beta-lactam antibiotics. Strains resistant or moderately resistant to benzylpenicillin, ampicillin, oxacillin, methicillin and cephalotin were detected. The majority of the strains were resistant to streptomycin, tetracycline and gentamicin. Multiple antibiotic resistance with 2-7 determinants was revealed in 11.2 per cent of the strains. The antibiotic sensitivity of the strains isolated from the newborns, their mothers and the personnel in the maternity home was on the whole similar or insignificantly differed.     

Structure of the antibiotic resistance of the salmonellae found in Transcarpathia]

Resistance of 1280 strains of Salmonella of various serological types isolated in the Zakarpatskaya region within 1967-1976 was studied with respect to benzylpenicillin, streptomycin tetracycline, levomycetin, monomycin, neomycin, erythromycin and oleandomycin. An Increase in the resistance of Salmonella to streptomycin, tetracycline, levomycetin, monomycin and neomycin was shown. During the last years Salmonellae carrying 4-8 resistance determinants were spreading in the region. Among S. typhimurium strains with 7-8 resistance determinants predominated (58.8 per cent). The cases of salmonollosis were mainly due to these strains.     

Antibiotic sensitivity of the bacterial microflora from the sputum of children with acute pneumonia]

Bacteriological analysis of sputum of 598 children with acute pneumonia was performed. Sensivity of 1348 cultures belonging to 8 bacterial species with respect to benzylpenicillin, streptomycin, chloramphenicol, tetracycline, oxytetracycline, chlortetracycline, erythromycin, oleandomycin, neomycin and monomycin was determined. It was shown that the sputum microflora was often resistant to the antibiotics widely used in the medical practice for prolonged periods of time, such as benzylpenicillin, streptomycin, chloramphenicol, tetracyclines. However, it usually remained sunsitive to neomycin, monomycin, erythromycin and oleandomycin. It was found that antibioticogrammes defining the antibiotic choice were of great significance for therapy of acute pneumonia.     

Effect of benzylpenicillin and tetracycline on the phagocytic, nonspecific humoral and biochemical activity of uninfected animals

The effect of benzylpenicillin and tetracycline on the activity, intensity and completion of phagocytosis with the leucocytes of the peritoneal exudate, on the activity of lysozyme and beta-lysins of the blood serum, on the content of nucleic acids, the activity of succinate dehydrogenase and total and acid phosphatase in the liver and kidney cells was studied experimentally on noninfected albino mice. The study showed that administration of benzylpenicillin and tetracycline to the animals for 5 days induced a decrease in the activity of the cell and humoral defence and the activity of the above enzymes in the liver and kidney cells. The content of the nucleic acids did not change under the effect of the antibiotics.     

Effect of antibiotics on the resistance of white mice to C1. perfringens toxin]

The effect of potassium benzylpenicillin, streptomycin sulfate and chlortetracycline on experimental gangrenous intoxication was studied. When the antibiotics were injected before intoxication, the albino mice resistance did not significantly change. When the antibiotics were injected immediately after the toxin administration, the resistance of the test animals markedly decreased.     

Acid hydrolase activity and cyclic nucleotide contents in the rat heart during myocardial ischemia and postischemic reperfusion

The acid phosphatase and cathepsin D activities and cAMP and cGMP levels in isolated perfused rat heart were investigated during various periods of ischaemic myocardial injury and postischaemic reperfusion. The effect of phosphodiesterase inhibitor--caffeine was also studied. Free acid hydrolases activities and cyclic nucleotide content were increased under 40 and 60 min ischemia and 20 min postischaemic reperfusion. Addition of 50 microM caffeine to perfusion solution after 30 min of ischaemia resulted in increase of cAMP level, cAMP/cGMP ratio, lysosomal bound activities of acid hydrolase and decrease of free acid hydrolase activities. The obtained results suggested that defect in cAMP synthesis might be present in lysosomal membranes labilization in cardiomyocytes injured during ischaemic conditions. Addition of such agents, as caffeine, which increased heart cAMP level, may be effective in lysosomal membranes stabilization under reversible heart ischaemia and reperfusion.     

Antibiotic interaction with proteolytic enzymes]

The effect of penicillin, tetracycline, aminoglucozide antibiotics and streptomycin on BAEE-esterase activity of trypsin was studied. It was found that benzylpenicillin in amounts of 50, 100 and 300 mg, ampicillin in an amount of 25 mg, methicillin in an amount of 12 mg and tetracycline in an amount of 2.5 mg as calculated per 1 mg of trypsin had no effect in vitro on the esterase activity of the enzyme. Neomycin, kanamycin and streptomycin in amounts of 5, 10, 100 or 300 mg per 1 mg of trypsin catalyzed splitting of BAEE by trypsin. When the antibiotics were added to the bile, its esterase activity increased. Preliminary intramuscular administration of trypsin and kanamycin to the rats had no effect on the ampicillin levels in the blood serum and brain and did not affect the permeability of the hemato-encephalic barrier as compared to the use of trypsin alone.     

Effect of antibiotics on the resistance of white mice to infection caused by antibiotic-resistant Staphylococcus strains]

The effect of benzylpenicillin, streptomycin and tetracycline on the animal resistance to infection caused by the antibiotic resistant staphylococci was studied. It was found that the effect of the antibiotics on the infectious process outcome was not limited by their antibacterial properties. Changes in the natural resistance of the host under the effect of the antibiotics were not always the same and depended on both the antibiotic type and the moment of its administration.     

The peptidoglycan crosslinking enzyme system in Streptomyces strains R61, K15 and rimosus. Kinetic coefficients involved in the interactions of the membrane-bound transpeptidase with peptide substrates and beta-lactam antibiotics

The transpeptidation reaction performed by the membranes of Streptomyces strain R61 fits the general rate equation for an enzyme-catalysed bimolecular reaction. The same membranes (E) interact with beta-lactams (I) to form inactive penicillin-enzyme-membrane complexes (EI) of rather high stability, which subsequently break down (E + I leads to EI leads to E + degradation products). The enzyme is regenerated and the antibiotic is released in the form of an inactive metabolite. With benzylpenicillin, the degradation product is benzylpenicilloic acid. The reaction is heat-labile. The first step of the reaction (E + I leads to EI) is characterized by a second-order rate constant (kformation in M-1 s-1) and the second step (EI leads to E + degradation products) by a first-order rate constant (kbreakdown in s-1). The effects in vitro of various beta-lactams on the membrane-bound transpeptidase, as expressed by the relevant kformation and kbreakdown values, parallel the effects in vivo of the same antibiotics as expressed by their ability to prevent the germination and growth of conidiospores. The kinetic parameters of the transpeptidase that was solubilized with N-cetyl-N,N,N-trimethylammonium bromide with respect to its interaction with both peptide substrates and beta-lactam antibiotics are quantitatively different from those of the membrane-bound enzyme. Moreover, the solubilized enzyme fragments benzylpenicillin with formation of phenylacetylglycine, a reaction which is similar to that catalysed by the exocellular R61 enzyme. The membranes of Streptomyces strains rimosus and K15 possess an active 'classic' penicillinase. They were not studied but the kinetic coefficients of the corresponding solubilized transpeptidases were determined and compared with those of the solubilized enzyme from strain R61.     

Lysosomal and non-lysosomal factors in chemically induced chromosome breakage

The possibility that chemically-induced chromosomal damage is mediated through the mechanism of lysosomal labilization was investigated. The known chromosome breaking agents, mitomycin C and streptonigrin, showed no effect on lysosomal membranes as evidenced by both enzymatic and previous electron microscopic studies [7]. The combination of these drugs with known lysosomal stabilizing agents reduced the frequency of chromosome damage somewhat. However, chromosome damage was also reduced by exposure of cells to heat or cold. The known lysosomal labilizers, vitamin A alcohol and acid, did not increase the frequency of chromosome breakage in peripheral lymphocytes. Therefore, these studies fail to support the hypothesis that the destruction of lysosomal membranes and the subsequent release of hydrolytic enzymes are instrumental in the induction of chromosomal damage by mitomycin C and streptonigrin.     

Comparative biochemical study of 2 natural inactive variants of the actinomycin C producer Actinomyces sp. 26-115 with varying sensitivity to actinomycin

Two natural variants of the actinomycin C-producing organism Actinomyces sp-26-115, i.e. H1 and H2 differ in their sensitivity to exogenic actinomycin, colony morphology, growth dynamics on the synthetic medium and stability to ultrasound and lysozyme. Both variants synthesize no actinomycin. Variant H1 is sensitive to exogenic actinomycin, while variant H2 is resistant to it. Variants H1 and H2 have some similarity in the composition of membrane proteins. Still, they differ in the protein molecular masses, which are equal to 600000--500000, 220000, 130000. The active variant A and nonactive variant H2 have the most similar compositions of membrane proteins. These variants are also close in their growth dynamics, colony morphology, sensitivity to ultrasound and lysozyme. The membranes of all the variants studied contain phosphatidyl ethanol amide as the main phospholipid component. Insignificant differences are observed only with respect to the minor components. The content of teichoic acids in the cell walls of variant H2 is very high, slightly changes during the developmental stage and insignificantly increases on addition of actinomycin to the medium. The cell wall of variant H1 contains less amounts of teichoic acids. During the developmental stage they are liberated from the wall at a higher rate than peptidoglycan. The sensitivity to actinomycin does not increase with an increase in the culture age. It is probable that teichoic acid of the cell wall is one of the factors providing resistance to actinomycin in variant H2. It may be considered as a barrier preventing transport of exogenic actinomycin into the cell.     

Secretion of immune interferon and generation of cytotoxic T cell activity in nude mice are dependent on interleukin 2: age-associated endogenous production of interleukin 2 in nude mice

Human peripheral blood monocytes are heterogeneous with respect to their size and function. Two monocyte subsets were isolated by countercurrent centrifugal elutriation and were studied with respect to their ability to effect antibody-dependent cellular cytotoxicity (ADCC) and for the presence of Fc receptors on their surface. Both monocyte subsets display Fc surface receptors and are effectors of ADCC against sensitized human erythrocyte target cells. The demonstration of ADCC by monocyte effectors is dependent on their concentration in the incubation mixture. Dilution of monocytes below 10% by unlabeled and unsensitized erythrocytes or lymphocytes significantly suppresses ADCC, presumably by steric inhibition of effector and target contact.     

Liposomes expressing IL 1 biological activity

We determined the activity of IL 1, obtained from various human monocyte subcellular compartments, when associated with liposomes. Soluble IL 1, bound to the outer surface of lyophilized liposomes, stimulated responsive target cells. However, this activity was not preserved when soluble IL 1 was incorporated into the inner chambers of classical liposomes. In contrast, monocyte plasma membranes that exhibited IL 1 activity had the same level of activity when presented on lyophilized liposomes and when incorporated inside the classical liposomes. However, monocyte plasma membranes bound to the outer surface of the liposomes exhibited greater activity than the monocyte membrane IL 1 itself in its soluble form. This suggests that membrane IL 1 is an integral membrane protein, readily integrated into the lipid bilayers. Like soluble IL 1, the expression of IL 1 activity present in the cytosol of activated monocytes was decreased by incorporation into liposomes, but was high and active when presented on lyophilized liposomes. The best artificial cell reconstitution was obtained with lyophilized liposomes in association with monocyte cytosol and plasma membranes. When an unactivated monocyte compartment was mixed with one from an activated monocyte, the signal was equal to that of the activated cell compartment alone. The IL 1 activity of activated cell fractions associated with lyophilized liposomes was determined, and an increase of IL 1 activity for both plasma membranes and cytosol was observed, whereas a decrease of the signal was obtained for the lysosomal compartment. Endoplasmic reticulum showed no IL 1 activity, even after trypsin treatment. The highest activity after trypsin treatment was recovered in the cytosol associated with lyophilized liposomes, suggesting that molecules obtained after this treatment were able to bind tightly to the lipid bilayers.     

Biochemical investigation of the functional state of various subcellular structures as a criterion for the assessment of unfavourable effects of environmental factors

Theoretical basis and results of biochemical studies of the enzymic systems of different localization in the cell--both bound with subcellular structures lysosomes--and dissolved in the cytosol--during experimental exposure to some environmental factors (carbon tetrachloride, carbon disulphide and others) are presented. It has been suggested to employ the assessment of the functional state of biomembranes of cellular organelles (e. g. lysosomes) and especially the effect of solubilization of membrane-bound enzymes and labilization of lysosomal membranes as one of the biochemical criteria of hygienic assessment of toxic effects and of some forms of delayed effects of environmental contaminants. Simultaneous biochemical investigation of enzyme-markers of subcellular organelles in the tissues of various organs and in biological fluids (blood, urine, seminal and amniotic fluids) permits us to elaborate and recommend for use in hygienic practice new biochemical criteria of unfavourable biological effects of chemical factors of the environment.     

Antibiotic sensitivity of the causative agents of suppurative surgical infection]

Sensitivity of 1492 strains of the causative agents of the surgical purulent infections, i. e. pathogenic Staphylococcus, Proteus, Ps. aeruginosa and E. coli to benzylpenicillin, streptomycin, levomycetin, tetracycline, erythromycin, oleandomycin, monomycin, kanamycin, novobiocin, ampicillin, oxacillin, ceporin, gentamicin and rifampicin was studied. Gentamicin was most active against all the bacterial species tested. The staphylococci were in addition sensitive in a high percentage of the cases to rifampicin, novobiocin, ceporin, monomycin and kanamycin. The isolates of E. coli were in addition sensitive to ceporin, monomycin and kanamycin. Sensitivity of the strains of Ps. aeruginosa and Proteus was low to all of the antibiotics except gentamycin. Most of the strains of the causative agents of the surgical purulent infections were multiresistant to 4 antibiotics. The number of the staphylococcal strains sensitive to benzylpenicillin, streptomycin and levomycetin increased in 1976 as compared to 1975 on the background of a limited use of these antibiotics in clinics.     

Action of penicillin on the erythrocyte membrane

The effect of the therapeutic concentrations of benzylpenicillin on potassium release and osmotic resistance of the red blood cells in healthy children was investigated potentiometrically with the use of a K+-selective electrode. In a concentration of 0.66 mM (370 units/ml) benzylpenicillin increased the total content of potassium in the cells and their resistance to osmotic lysis and lowered the rate of K+ release induced by valinomycin. The membrane stabilizing effect of benzylpenicillin observed in these studies could to some extent stipulate its nonspecific antiinflammatory effect. In a concentration of 1.32 mM (740 units/ml) it had no significant effect on the indices studied. Under the effect of the maximum concentrations of the antibiotic (3.3 mM) the signs of lowered stability of the red blood cell membranes were observed, i.e. an increased rate of the valinomycin induced release of K+ and a tendency for the decreasing of the osmotic resistance.