Effect of Pseudomonas aeruginosa melanin on antibiotic activity]

The properties of microbial melanines are very diverse. Melanine of P. aeruginosa is little studied. The pigment was isolated from a strain of P. aeruginosa possessing all characteristic properties of the species. Interaction of P. aeruginosa melanine with various antibiotics was determined by the method of serial dilutions in beaf-peptone broth, using Staph. aureus 209 as a test-microbe, which was added to the medium in an amount of 10(6) cells to each tube. It was found that P. aeruginosa melanine differed from DOPA-melanine in a concentration of 1 mg/ml and did not change the activity of penicillin, tetracycline, oleandomycin, kanamycin and gentamicin with respect to Staph. aureus.     

Thrombolytic activity of terrilytin and its effect on the coagulating system of the blood]

The preliminary incubation of fibrinogen with terrilytin in vitro delayed the formation of the clot and accelerated the subsequent lysis. Terrylitin (in vitro) prolonged the recalcification time, lowered the thromboplastic activity and that of fibrinase, and also enhanced the fibrinolytic activity of the blood plasma. In experiments on dogs roentgenovasography revealed a considerable thrombolytic activity of terrilytin following its intravenous infusion to the animals with experimental thrombosis of the femoral veins.     

Extracorporeal immunostimulating effect of terrilytin and lysozyme]

The role of splenocytes and erythrocytes in showing an extracorporal action by terrilytin and lysozyme was studied. The extracorporal effect of terrilytin was to a greater extent mediated by the spleen cells adhering to the plastic while the extracorporal effect of lysozyme was mainly mediated by the heavy ("old") erythrocytes. The heat treatment at a temperature of 42 degrees C for 15 minutes did not abolish the terrilytin extracorporal effect mediated by the erythrocytes but completely abolish the similar effect induced by lysozyme which bound to the erythrocyte membrane. After exposure of the erythrocytes to terrilytin, the strength of the lysozyme binding increased and there was a respective increase in the immunostimulating activity of the erythrocytes.     

The effect of fetal bovine serum on polyene macrolide antibiotic cytotoxicity and antifungal activity

Summary The relationships between fetal bovine serum (FBS) concentration and polyene macrolide antibiotic cytotoxicity to animal cells and to fungi were evaluated. The toxicity of amphotericin B (AB) and its derivative, amphotericin B methyl ester (AME), toward KB cells was found to be directly related to fetal bovine serum concentration. At higher FBS levels, increased concentrations of AB and AME were required to reduce 72-hr KB viable cell numbers to 50% of control values. Similarly, polyene macrolide antibiotic levels required to inhibit the growth ofSaccharomyces cerevisiae to 50% of controls, and for obtaining minimum fungicidal concentrations (MFC), were greater when higher levels of FBS were used. In addition, AME was less toxic than AB toward KB cells grown in media containing 2, 5, 10, 15 or 20% FBS, whereas the antifungal activities of AB and AME were similar. AME was also capable of eliminatingCandida albicans, Saccharomyces cerevisiae, Aspergillus niger orFusarium moniliforme from KB cultures at antibiotic levels which exhibited less cell toxicity than did the concentrations of AB required for a similar response. These findings indicate that AME may be a potentially useful antifungal antibiotic for tissue culture systems. Portions of this paper were presented at the 25th Annual Meeting of the Tissue Culture Association at Miami, Florida, 1974. This investigation was supported in part by contract NIH 69-2161, NIH grant no. AI-02095 and NIH training grant no. GM 507 from the National Institute of General Medical Sciences.     

Effect of protoplasting on antibiotic activity and resistance in the strain Streptomyces hygroscopicus 155]

The influence of protoplasting and protoplast regeneration in the presence of polyethylene glycol on antibiotic activity, components of antibiotic complexes and antibiotic resistance in Streptomyces hygroscopicus 155 was studied. It was shown that the protoplasting and protoplast regeneration influenced the antibiotic activity. The protoplast fusion resulted in increased isolation of variants with higher antibiotic activity. The processes also affected the components of the antibiotic complexes but had no effect on the strain resistance to some antibiotics.     

Effect of terrilytin on the activity of nonspecific resistance factors during immunization with staphylococcal anatoxin and staphylococcal infection

Terrilytin and immobilized terrilytin enhance the activity and intensity of phagocytosis and increase the concentration of lysozyme in nonimmunized animals. Both preparations increase the production of antibodies to staphylococcal alpha-hemolysin, the titers of beta-lysins, the activity and intensity of the phagocytosis of bacterial cells by peripheral blood leukocytes in animals immunized with staphylococcal toxoid and challenged with live staphylococcal culture. In healthy animals terrilytin and immobilized terrilytin induce an increase in total proteolytic activity and in the activity of alpha-1-antitrypsin and alpha-2-macroglobulin, decreased as the result of staphylococcal infection.     

家蝇幼虫血淋巴中抗真菌肽的诱导方法比较及抗真菌活性

以未诱导组作为空白对照研究比较真菌诱导、超声诱导和热诱导家蝇Musca domestica 幼虫血淋巴初提液的抗真菌肽效果,比较各种诱导方法诱导后的幼虫存活率;用凝胶层析法和高效液相分离纯化热诱导家蝇3龄幼虫抗真菌肽,检测其抗白假丝酵母菌Candida albicans和新生隐球菌Cryptococcus neoformans活性;SDS-PAGE分析抗真菌肽的蛋白分子量范围。结果表明：3种诱导方法诱导后家蝇幼虫均产生具有明显抗真菌作用的抗真菌肽,其初提液抑菌圈大小没有明显差别;真菌诱导组和热诱导组幼虫存活率低于对照组,而超声诱导组与对照组相比则无明显差别。经分离纯化后,抗真菌肽仍具有较好的抗真菌活性;SDS-PAGE分析表明该抗真菌肽有效成分的蛋白分子量在14.4 kD以下。结果提示热诱导家蝇幼虫产生抗真菌肽是一种方便、有效的诱导方式。     

Effect of liquid culture requirements on antifungal antibiotic production by Streptomyces rimosus MY02

Streptomyces rimosus MY02 was isolated from a soil sample which was collected from the northeast of China. The effect of medium components (i.e. carbon and nitrogen sources) and other culture requirements (i.e. initial pH and temperature) on production of antifungal antibiotics by S. rimosus MY02 was investigated in our work. The best conditions for the strain MY02 in 250-ml Erlenmeyer flask, for example, initial pH, temperature, medium capacity, agitation rate, seed age, inoculum size and growth period, were 6.0, 28 degrees C, 50 ml, 180 rpm, 4 days, 10% (v/v) and 120 h, respectively. Components and dosage of the medium, which effect antibiotic production, were determined by uniform design combined with regression analysis; meanwhile, a regression model was established. The components and dosage of the best medium were starch, 53.313 g; defatted peanut powder, 9.376 g; (NH(4))(2)SO(4), 6.244 g; and NaCl, 5.836 g; in 1l of distilled water. Residual values obtained between the observed values by experiments and predicted values by the model are very low, and this result showed that the experimental results were well in consistence with the calculation results via the model. The antifungal antibiotic production by S. rimosus MY02 was improved by optimization of the components and culture requirements. The diameter of inhibition zone of the culture supernatant from S. rimosus MY02 against Fusarium oxysporium f sp. cucumarinum was 33.19 mm.     

The extracorporeal immunostimulating effect of terrilytin in staphylococcal infection]

The intravenous injection of terrilytin-treated lymphocytes into rats infected with staphylococci enhances the formation of staphylococcal alpha antitoxin in the animals and the development of immune response to T-dependent antigen, such as sheep red blood cells (SRBC), but produces no effect on the development of immune response induced by T-independent antigen (lipopolysaccharide). Terrilytin-treated lymphocytes induce the release of the factor promoting the development of immune response to staphylococcal antigens and SRBC by spleen cells, incapable of adherence to plastic, but have no influence on the development of immune response to lipopolysaccharide in rats infected with staphylococci. At the same time in such rats spleen cells adhering to plastic take part in the transfer of signals from terrilytin-treated lymphocytes to nonadhering spleen cells of recipients.     

Antitumor activity of carminomycin antibiotic used orally]

Antitumor activity of karminomycin used perorally was studied with respect to 3 strains of mouse transplantable tumors, i. e. one ascitic strain of lymphadenosis NK/LI and two solid strains of lymphosarcoma L10-1 and sarcoma 180. Karminomycin was shown to have a high antitumor activity against the above tumors on its oral administration. In the experiments with lymphadenosis NK/LI the efficiency of karminomycin was higher when it was used perorally as compared to its intravenous administration. It was found that karminomycin had practically the same inhibitory effect on growth of lymphosarcoma L10-1 and sarcoma 180 on its peroral and intravenous administration in doses equivalent by their toxicity.     

Effect of coamide on immunogenesis during antibiotic therapy]

The dynamics of the antibody-producing cells in the spleen and the titer of hemagglutinines in the blood of albino mice immunized with sheep erythrocytes and treated with various doses (250, 500, 1000 gamma) of oxytetracycline and monomycin and their combinations with coamide, a complex of cobalt with nicotinic acid amide at different periods after the immunization. It was found that oxytetracycline in doses of 500 and 1000 gamma and monomycin in doses of 250, 500 and 1000 gamma administered intramuscularly for 4 days had an inhibitory effect on both the antibody-producing cells and the titer of hemagglutinines in the immunized animals at various periods after the immunization. Consequently, oxytetracycline and monomycin had the immunosuppressive effect. Exposure of the animals treated with oxytetracycline and monomycin to coamide for 5 days provided an increase in the number of the antibody-producing cells and the titer of the hemagglutinines. The results of the study showed the perspectivity of coamide use in complex therapy of infectious diseases.     

Effect of a modified terrilytin on ampicillin pharmacokinetics in experimental peritonitis

The effect of modified terrilytin, a new enzyme of the microbial origin on the pharmacokinetics of ampicillin in experimental peritonitis was studied on 16 pubertal rabbits. Peritonitis was caused by laparotomy and administration of a 15 per cent fecal suspension into the abdominal cavity. The drugs were injected intramuscularly: the enzyme in a dose of 5 PU/kg and the antibiotic in a dose of 10 mg/kg. The ampicillin levels in the blood and peritoneal exudate were determined with the agar-diffusion method. The specimens were collected 30 minutes, 1, 1.5 and 2 hours after administration of the drugs. The animals were divided into 2 groups: control (not treated with the enzyme) and experimental. An increase in the antibiotic levels in the blood and peritoneal exudate by 50--54 per cent was observed. The maximum increase was recorded 30 minutes after simultaneous administration of the drugs.     

Molecular modelling of membrane activity of amphotericin B, a polyene macrolide antifungal antibiotic

Amphotericin B (AmB) is a well known polyene macrolide antibiotic used to treat systemic fungal infections. Despite its toxicity AmB is still regarded as a life-saving drug. The lack of adequate knowledge of the AmB mechanism of action is a serious obstacle to efficient development of new less toxic derivatives. Complementary to various experimental approaches, computational chemistry methods were used to study AmB mechanism of action. A programme lasting for a decade, that was run by our group covered studies of: i) molecular properties of AmB and its membrane targets, ii) structure and properties of AmB membrane channels, and iii) interaction of AmB with the membrane.     

Effects of the new antifungal antibiotic mucidin

The antibiotic activity of the antifungal substance mucidin was compared with the activity of nystatin and pimaricin. The antibiotics were tested by the plate method using 19 fungal species, mainly phytopathogenic ones. Toward 14 species, mucidin was ten times more active than nystatin and pimaricin, toward 5 species the activities were roughly the same. The antibiotics differed also in the sharpness of the inhibition zone boundaries.     

Effects of the new antifungal antibiotic mucidin

The morphological changes in 19 fungal species (16 filamentous fungi and 3 yeasts) caused by the antifungal antibiotic mucidin (trade mark Mucidermin Spofa) were examined. The filamentous fungi showed an undulation and ramification of hyphae and thickening of cells. The yeastCandida pseudotropicalis changes the shape and size of cells and the structure of cytoplasm.