Optimal combined use of rifampicin and immunomodulator of microbial origin in experimental Q-Rickettsia infection

Multifactorial analysis of the combined use of rifampicin and an immunomodulator of the microbial origin, such as peptidoglycan, was performed on a model of experimental Q fever in albino mice. On the basis of the experimental results, statistic polynomial models describing the weight of the murine spleens and the titers of the complement-binding antibodies were designed. It was shown that the action of the immunomodulator and antibiotic was highly synergistic with respect to the chemotherapeutic activity and antibody titers. The preventive use of the immunomodulator yielded a 30-fold decrease in a rifampicin therapeutic dose. The use of the immunomodulator also provided a pronounced immunomodulating effect with respect to humoral immunity. Nomographs for optimizing the dose-time parameters of the antibacterial and immunomodulating therapy were plotted.     

Comparative multifactorial analysis of combined administration of injection and peroral forms of an antibiotic with a microbial immunomodulator in experimental anthrax

Comparative efficacy of the use of injection and oral dosage forms of rifampicin in the subtherapeutic doses in combination with peptidoglycan , an immunomodulator of microbial origin, was studied in respect to experimental anthracic infection with application of multifactorial analysis. It was shown that the antibiotic and immunomodulator had a pronounced synergistic effect. Polynomial statistic models were developed and nomograms or equal level curves defining the survival rate and average life-span (ALS) of the experimental animals within a wide range of the antibiotic and immunomodulator doses and the peptidoglycan dosing time were plotted. The combined use of the injection rifampicin in the subtherapeutic doses and the immunomodulator provided a significant increase in the survival rate and ALS, whereas the use of the oral antibiotic in combination with the immunomodulator increased only the ALS and not the survival rate. Multifactorial analysis proved to be an optimal methodical approach to comparative study of various antibiotic dosage forms used in combination with immunomodulators under experimental conditions.     

Multifactor analysis of the combined use of an antibiotic and a low molecular weight immunomodulator of microbial origin in experimental plague infection

Multifactorial analysis of the combined effect of rifampicin and a low molecular immunomodulator of microbial origin in experimental plague infection was performed. Synergism of the antibiotic used in the subtherapeutic doses and the immunomodulator was shown. By the results of the study polynomial statistic models of the second order describing the survival rate and average life-span of the experimental animals were developed and nomographs (equal level curves) were plotted for rapid estimating the therapy quantitative parameters. Optimization of the combined use of rifampicin and the immunomodulator on the basis of the multifactorial analysis was achieved.     

Multifactorial experiment on the combined action of doxycycline and a low molecular weight immunomodulator of microbial origin in experimental anthrax infection

Chemotherapeutic efficacy of combined therapy of experimental anthrax infection with subtherapeutic doses of doxycycline and a low molecular weight immunomodulator of microbial origin was studied with mathematical design of the experiment and multifactorial analysis. A marked synergistic effect of oral doxycycline and the immunomodulator was observed. The results of the multifactorial experiment were computer processed and polynomial statistic models (the second order equations) describing the survival rate and mean lifespan (MLS) were derived. The equal level lines characterizing the survival rate and MLS were plotted against the fixed values of the time factor of administering the immunomodulator and the dose of the antibiotic. The doses of the immunomodulator and the time of its administration were optimized with respect to the maximum therapeutic effect with doxycycline subtherapeutic doses.     

Multifactor analysis of parameters of immunity under the combined action of doxycycline and a low molecular weight immunomodulator of microbial origin

The effect of doxycycline combination with a low molecular immunomodulator of microbial origin on the primary immune response to the vaccine EV antigens was studied in multifactor experiments. Mathematical processing of the data provided construction of polynomial statistic models of the second order describing increased delayed type hypersensitivity (IDTH) and the antibody titer. Analysis of the quasimonofactor models revealed different character of regulation of the cellular and humoral response. Nomograms were plotted for precise quantitative estimation of the dose-time parameters of the regimens for combined use of the antibiotic and immunomodulator providing the required levels of IDTH and the antibody titer.     

Multifactorial experiment on the combined effect of rifampicin and microbial polysaccharide in experimental plague infection

Multifactorial analysis was applied to the study of the combined effect of rifampicin and a microbial polysaccharide in experimental plague infection. The effect of the antibiotic and immunomodulator was shown to be synergistic. On the basis of the study results polynomial statistic models of the second order were designed and nomograms or equal level lines were plotted which provided optimization of the combined chemo- and immunotherapy.     

Effect of Halococcus morrhuae and Halobacterium saccharovorum on the activation of human peripheral blood lymphocytes.

The immunomodulator properties of two species of halophilic Archaebacteria, Halobacterium saccharovorum and Halococcus rnorrhuae, were analysed by the study of lymphocyte activation. Two methods were used to detect activation in lymphocytes, namely incorporation of the radioactive nucleotide [3H]-thymidine, and CD25 expression. H. morrhuae had a stimulatory effect on human lymphocytes, but this action was observed only with the [3H]-thymidine uptake method, whereas H. saccharovorum produced no immunomodulator effect.     

In Vitro Activity of Lincomycin and Spectinomycin Against Serotypes of Avian Mycoplasma

Twenty strains of avian mycoplasma, representing 12 serotypes, were tested in vitro for their susceptibility to the action of lincomycin and spectinomycin alone and in combination. They varied in their sensitivity pattern. The ranges of minimal inhibitory concentration were 1 to 20 mug/ml for lincomycin or spectinomycin alone and 0.5/1 to 3/6 mug/ml for the lincomycin and spectinomycin combination. The ranges of minimal lethal concentration were greater with either single antibiotic than with the antibiotic combination. The amount of each antibiotic required to achieve mycoplasmacidal action of the relatively resistant strains was less with the antibiotic combination than with the single antibiotics.     

The action of its own antibiotic on the producer of imbricin growing on an agarized medium]

The action of imbricin on its own producer Streptomyces imbricatus grown on an agarized medium was studied. Comparatively low concentrations of the antibiotic were shown to have a high lethal action on the streptomycete. The morphological and cultural features of S. imbricatus did not change under the action of imbricin while the variation with respect to the antibiotic production property markedly increased. After the strain exposure to 200 micrograms/ml of imbricin, a stable variant with the antibiotic potency 20 per cent higher than that of the initial organism was isolated.     

Effect of taktivin on diuresis and tubular cardiotrast secretion in the kidney

The effect of a new immunomodulator taktivin (7-20 micrograms/kg subcutaneously, for 6 days) on the diuresis and tubular transport of cardiotrast (diodrast) was studied on rats. taktivin was shown to increase the tubular transport of the xenobiotic without significant changes in glomerular filtration and renal excretion of water, sodium, potassium, uric acid and creatinine. Possible mechanism of taktivin's action on the tubular transport of xenobiotics is discussed.     

General toxic and organotropic properties of cefotaxime in acute and chronic experiments

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.     

Accumulation in the regenerating liver of hepatocytes with pathological nuclei as affected by daunorubicin

The action of the antitumor antibiotic rubomycin on dividing cells in the regenerating liver was studied. The antibiotic was administered 2 hours before partial hepatectomy in single doses of 1 to 8 mg/kg. It was shown that any of these doses provided equal suppression of the cell division. Mitosis always started on the 5th or 6th day. Various forms of mitosis pathology were observed. On the 7th day after the partial hepatectomy there was detected a large number of pathologically changed nuclei in the liver. With an increase in the rubomycin dose their number increased. With an increase in the dose there was also observed a large number of affections associated with impairment of the mitotic apparatus. After some time the morphologically visible nuclear disorders in the population disappeared. In six months there were practically no pathological nuclei in the liver. Three aspects of the antibiotic action i.e. toxic action, cytostatic action and induction of chromosomal aberrations are discussed. The toxic action and induction of chromosomal aberrations increased with increasing the drug dose while the cytotoxic action did not change.     

Liposomes: A Promising Future for Dermatocosmetology and Clinical Dermatology

Abstract

The narrow link between skin and liposomes comes from the observation that, contrary to the medical field, which presumes a parenteral introduction, in the dermatological field liposomes are applied directly on the part where they are destined and with which there is a strong affinity. At first liposomes have been used in the dermo-cosmetological field because of their restoring and moisturizing action. Furthermore the capability of liposomes to deliver active principles into the skin, releasing them in the deep layers, has consistently widened its action. Liposomes are presently used in antiaging, anti stretch marks, moisturizing and anticellulitis products; further use of liposomes can be envisaged as regards solar products, microcirculatory supply and cutanoeus imperfections characterized by erythrosis or capillary alterations. Liposomes have proven to be very useful for the therapy of certain dermatoses, such as atopic dermatoses or psoriasis. The advantage of incorporating a pharmaceutical substance (antibiotic, cortisone, immunomodulator, antimycotic, antiviral) can be observed in more effective and shorter therapy together with a decrease of side effects both local and linked to the systemic assimilation. Studies with acyclovir, interferon and topic steroids (triamcinolone and hydrocortisone) have been carried out experimentally. It is certain that a substance will have a different destiny when delivered by a liposome rather than by a normal eccipient.     

Differential Effects of Monovalent and Divalent Ions upon the Mode of Action of the Polyene Antibiotic Candicidin

The polyene antibiotic candicidin is a potent membrane active agent, the action of which can be inhibited by the presence of certain ions. The destruction of the selective permeability of yeast membranes by candicidin allows small molecules to leak into the environment. Loss of intracellular potassium ions inhibits yeast glycolysis. This inhibition may be reversed by extracellular concentrations of potassium or ammonium ions. Monovalent ions did not prevent antibiotic absorption or protect yeast growth from the action of the antibiotic. Divalent ions did not protect yeast glycolysis from the action of candicidin, but were able to reduce antibiotic-induced membrane damage and allowed yeast growth in the presence of antibiotic. It is suggested that divalent ions may interact with membrane sterols creating steric hindrance to subsequent candicidin absorption.     

免疫调节剂的研究及应用进展

免疫调节剂是能调节免疫功能的药物,在临床上能够有效的治疗与免疫有关的疾病。免疫调节剂的作用是增强或抑制免疫功能,可以根据来源不同进行分类。免疫调节剂的作用主要是影响免疫系统中任一环节的反应和作用,如刺激免疫细胞的功能或是拮抗免疫分子发挥作用。免疫调节剂在临床上应用广泛,肿瘤、器官移植、类风湿性关节炎等的治疗都依赖于免疫调节荆的作用。因此,研究免疫调节剂的作用机理、开发有效的免疫调节剂具有重要的意义。免疫调节剂的发展将为人类健康带来新的希望。     

Mutagenic effect of mitomycin C on different strains of oleandomycin producer Streptomyces antibioticus

Mitomycin C, a DNA-tropic antibiotic, was shown to have a lethal effect on spore sprouts of two strains of Streptomyces antibioticus, an organism producing oleandomycin. When the time of exposure to the antibiotic increased there was an almost equal decrease in the survival rate. The mutagen action on the morphological variation and antibiotic production of the two closely related strains were diverse due to their genetic differences. The strain isolated after the culture treatment with a chemical mutagen and subjected to a more prolonged maintaining selection showed lower variation with respect to its colony morphology. The other strain isolated after treatment of the culture with high concentrations of its own antibiotic showed lower variation with respect to its antibiotic production property. The shift in the antibiotic production in the direction of the low active variants was characteristic of the both highly productive strains.     

Effect of antibiotic resistance on the appearance of mutants in a culture of Streptomyces cremeus subsp. tobramycini producing an aminoglycoside complex

Possible formation of auxotrophs and changing of the antibiotic production property connected with resistance to antibiotics of different modes of action were studied in Streptomyces cremeus subsp. tobramycini producing the nebramycin complex of 2-desoxystreptamine derivatives. Four hundred and five spontaneous and 1800 gamma-radiation induced antibiotic resistant mutants of the culture were studied. The frequency of the auxotrophs was shown to be increasing. Correlation between formation of strains producing monocomponent aminoglycosides and antibiotic resistance was observed. The frequency of mutants with preferable synthesis of the tobramycin component among strr-, rifr- and rubr-mutants was 3--10 times higher than among the sensitive portion of the population when total selection was used. Therefore, the spontaneous mutation of antibiotic resistance is selective with respect to both isolation of auxotrophs and strains producing separate aminoglycoside antibiotics.     

The effect of an artificial magnetic field on Salmonella infection in mice]

Experimental Salmonella infection in mice, developing simultaneously with the prolonged action of an artificial constant magnetic field with induction equal to 3 x 10(-4) T, was found to induce a pronounced decrease in nonspecific resistance in the animals. The study of Salmonella population structure revealed that the cells selected the animals subjected to the action of the artificial magnetic field had mostly a lesser number of signs of antibiotic resistance. By the end of the experiment Salmonella cultures isolated from the mice subjected to the action of the artificial magnetic field were characterized by greater virulence and resistance to the bactericidal action of blood serum. The use of sodium nucleinate under the conditions of the action of the artificial magnetic field enhanced the level of anti-infectious protection in the animals, which changed the direction of cell selection in Salmonella population towards cells with a greater number of markers of antibiotic resistance.     

Validation of antibacterial mechanism of action using regulated antisense RNA expression in Staphylococcus aureus

Validation of antibiotic mode of action in whole bacterial cells is a key step for antibiotic drug discovery. In this study, one potential drug target, enoyl-acyl carrier protein reductase (FabI), an essential enzyme in the fatty acid biosynthesis pathway, was used to evaluate the feasibility of using a regulated antisense RNA interference approach to determine antibiotic mode of action. Antisense isogenic strains expressing antisense RNA to fabI were created using a tetracycline-regulated vector in Staphylococcus aureus. We demonstrated that down-regulation of FabI expression by induction of fabI antisense RNA induces a conditional lethal phenotype. In contrast, partial down-regulation gives a viable cell with a significant increase in sensitivity to FabI-specific inhibitors (i.e., a sensitized phenotype). More importantly, the mode of action for novel FabI inhibitors has been confirmed using this genetic approach in whole cell assay. These results indicate that controlled antisense technology provides a robust tool for defining and tracking the mode of action of novel antibacterial agents.     

Inhibition of the growth of Escherichia coli by chlortetracycline

1. This study extends previous work concerned with the ribonucleic acid made by Escherichia coli during inhibition of protein synthesis by chlortetracycline. 2. The antibiotic caused an initial stimulation in the rate of RNA synthesis. 3. RNA made during inhibition was stable during continued incubation in the presence of the antibiotic although it was extensively degraded in resting cell suspensions. 4. Most of the RNA accumulated during chlortetracycline action was in particles that sedimented more slowly than ribosomes. During the recovery of cells from the effects of the antibiotic, accumulated RNA was apparently not degraded and ribosomes were synthesized from the RNA in the particles.