Multifactor analysis of the combined action of doxycycline and a peptidoglycan of microbial origin on the immune response

Multifactorial analysis of the combined action of a microbial peptidoglycan and doxycycline on the immune response to antigens of the vaccine EV fraction 1 was made. Nomograms or equal level curves characterizing delayed hypersensitivity (DH) and antibody titers in various doses of the peptidoglycan and the antibiotic were plotted by the experimental data with a computer. The peptidoglycan had a pronounced immunomodulatory action on DH and antibody titers. However, the types of regulation of the both responses markedly differed. With multifactor analysis, the range of the values of the operating parameters, i.e. the drug doses and the time of their administration providing the required levels of DH and antibodies under the conditions of the combined therapy were defined.     

Multifactorial analysis of combined use of an antibiotic and peptidoglycan of microbial origin in experimental plague]

The combined effect of doxycycline and microbial peptidoglycan was studied with multifactorial analysis. The drugs were used preventively and therapeutically. The preventive use of doxycycline in the subtherapeutic doses in combination with the immunomodulator resulted in a significant increase in the survival rate rather than the average life-span (ALS) of the experimental animals. The therapeutic use of the drugs was more efficient than the preventive one and resulted in higher survival and ALS. By the results of the experiments polynomial statistic models of the second order were developed and the equal level curves characterizing the survival rate and ALS were plotted. The dose-time regimens of the combined use of doxycycline an peptidoglycan were optimized.     

Immunomodulating action of peptidoglycan of microbial origin]

The action of a high molecular weight peptidoglycan produced by Agrobacter radiobacter sp. on the functional activity parameters in leukocytes and macrophages i. e. chemotaxis and adhesion was studied. It was shown that the peptidoglycan had a stimulating action on the chemotaxis of cells of the peritoneal exudate. A marked stimulating action of the drug on the primary immune response to the tissue antigen of sheep erythrocytes was observed. The peptidoglycan stimulated the antibody titers and delayed hypersensitivity when administered in various periods after an antigenic stimulus. Multifactorial experiments on the protective action of the peptidoglycan in experimental infections were carried out. Second-order polynomial statistic models characterizing the animal survival rate were constructed and the dose-time parameters of the drug use were optimized.     

Multifactorial study of the combined effect of rifampicin and microbial peptidoglycan in experimental plague infection

The combined effect of rifampicin and a microbial peptidoglycan was studied in multifactorial experiments on noninbred mice with plague infection. The effect of rifampicin and the immunomodulator was shown to be synergistic. The results of the multifactorial experiments provided designing of polynomial statistic models of the second order characterizing the animal survival rate and mean life-span and plotting of nomograms or equal level lines useful in optimization of the combined therapy parameters.     

Multifactor immunopharmacological analysis. Effect of rifampicin and low-molecular immunomodulator of microbial origin on the primary immune response to fraction 1 of vaccine EV

Multifactor analysis was applied to combined effect of a low molecular immunomodulator of microbial origin and rifampicin on the primary immune response (increased delayed type hypersensitivity and antibody titer) to the antigens of vaccine EV fraction I. Computer processing of the experimental data provided construction of the 2nd order polynomial models satisfactorily describing cellular and humoral responses in the combined therapy. For increasing the informative capacity of the analysis of the polynomial statistic models it was proposed to develop quasimonofactor relationships reflecting the factor effect on the output with changing of the other factors within the studied ranges. Nomograms (equal level lines at fixed values of one factor) were constructed which provided rapid and correct estimation of optimal values for the regulating parameters (drug doses and administration time). Immunostimulating activity of the microbial immunomodulator was estimated quantitatively and conditions for selective regulation of the cellular and humoral responses were determined.     

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.     

Evolutionary origin of peptidoglycan recognition proteins in vertebrate innate immune system

Background  

Innate immunity is the ancient defense system of multicellular organisms against microbial infection. The basis of this first line of defense resides in the recognition of unique motifs conserved in microorganisms, and absent in the host. Peptidoglycans, structural components of bacterial cell walls, are recognized by Peptidoglycan Recognition Proteins (PGRPs). PGRPs are present in both vertebrates and invertebrates. Although some evidence for similarities and differences in function and structure between them has been found, their evolutionary history and phylogenetic relationship have remained unclear. Such studies have been severely hampered by the great extent of sequence divergence among vertebrate and invertebrate PGRPs. Here we investigate the birth and death processes of PGRPs to elucidate their origin and diversity.     

Alpha-glucosidase inhibitors of microbial origin]

The data on spreading of inhibitors of alpha-glucosidases with microbial origin are given. Physiochemical characteristics of acorbose--a known inhibitor of alpha-glucosidases--and new inhibitor isolated from Streptomyces sp. are given in detail.     

Encapsulation of immunoadjuvant [24C]peptidoglycan monomer into liposomes: Effect on metabolism and immune response in mice

¹⁴C-labeled peptidoglycan monomer was encapsulated into negatively charged, multilamellar liposomes composed of egg phosphatidylcholine, cholesterol and dicetylphosphate. Excretion and tissue distribution of the label in mice were studied after intravenous injections. Encapsulation of peptidoglycan monomer into liposomes as compared to free peptidoglycan monomer, resulted in increased retention of the label, particulary in the liver and to a lesser extent in spleen. The excretion was drastically reduced and delayed even after 4 days when cholesterol-rich (phosphatidylcholine/cholesterol, 7:5 molar ratio) liposomes were used for encapsulation of peptidoglycan monomer. Peptidoglycan monomer and liposomes, when tested separately, stimulate the immune response to sheep erythrocytes in mice. However, there was no significant additive or synergistic effect when peptidoglycan monomer was encapsulated into liposomes.     

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 pefloxacin on immune response]

The influence on cellular immune response of different doses of the pefloxacin was studied in vivo as well as in vitro experiments. The pefloxacin in super bactericidal concentrations (2.0 mg/ml and 0.4 mg/ml) possess pronounced supressing effect the T-lymphocyte proliferation in blast transformation reaction. While in concentration 0.08 mg/ml pefloxacin does not show such activity. The pefloxacin in maximal effective concentration (200 mg/kg) suppressed activity in delayed hypersensitivity skin reaction of intact mice towards sheep erythrocytes on 20.3 percent only.     

微生物来源的酶抑制剂研究进展

１９５８年,植物学家Ｋｏｈｌａｎｄ首先提出次生代谢的概念,１９６０年Ｂｕ’Ｌｏｃｋ把这一概念引进微生物学领域。微生物次生代谢物包括抗生素、色素、毒素、信息素、动植物生长促进剂和生物药物素（ｂｉｏｐｈａｒｍａｃｅｕｔｉｎ）等。其中生物药物素包括酶抑制...     

Regulation of the immune response to tumor antigen. VIII. The effects of host specific anti-I-J antibodies on the immune response to tumors of different origin

The efficiency of in vivo therapy using alloantisera produced to interact specifically with I-J subregion encoded determinants has been investigated in two etiologically distinct syngeneic tumor systems, both of which have been shown to evoke suppressor T-cell host responses. Administration of 2 μl/day of anti-I-J^k alloantisera caused a significant reduction in the growth of the P815 methylcholanthrene (MCA)-induced mastocytoma or the 1316 ultraviolet (uv) radiation-induced fibrosarcoma in the syngeneic host. Inhibition of tumor growth with anti-I-J antibody treatment occurred in normal as well as in subcarcinogenically uv-treated hosts given the uv-induced 1316 fibrosarcoma, even though the normal host is capable of spontaneously rejecting the tumor graft in the absence of external manipulation. Evidence is also provided that the effects of anti-I-J antibody treatment are not due to direct interactions with the tumor cells, or to contaminating antiviral antibody activity within the antiserum. We have previously demonstrated the reduction of tumor growth in two antigenically distinct MCA-induced tumor systems (S1509a, SAI) using similar treatments. The data presented herein thus reinforce the possibility that such means of therapy may be beneficial to the treatment of a wide variety to tumor types where suppression represents a detrimental component of the host response, and may also provide some insight into the mechanisms underlying the effects of uv radiation on the immune response to tumor antigen.     

Experimental study of protease C--proteolytic enzyme of microbial origin]

The specific activity of protease C, a proteolytic enzyme isolated from Acremonium chrysogenum was studied under experimental conditions. Protease C was shown to lyse necrotic biological substrates (dry crusts of burn wounds) and blood clots. By the nature of the effect protease C was analogous to terrilytin and by the level of the effect it was superior in some experiments. Protease C was low toxic and had no mutagenic action.     

Innate immune response in insects: recognition of bacterial peptidoglycan and amplification of its recognition signal

The major cell wall components of bacteria are lipopolysaccharide, peptidoglycan, and teichoic acid. These molecules are known to trigger strong innate immune responses in the host. The molecular mechanisms by which the host recognizes the peptidoglycan of Gram-positive bacteria and amplifies this peptidoglycan recognition signals to mount an immune response remain largely unclear. Recent, elegant genetic and biochemical studies are revealing details of the molecular recognition mechanism and the signalling pathways triggered by bacterial peptidoglycan. Here we review recent progress in elucidating the molecular details of peptidoglycan recognition and its signalling pathways in insects. We also attempt to evaluate the importance of this issue for understanding innate immunity.     

Mathematical model of the immune response]

A model of immune reaction is suggested, ahich takes into account the delay in the development of an immune response. The model depending on parameters values describes: an asymptotic decrease of antigene quantity, approach of its quantity towards constant value, periodic course of the illness, unlimited growth of the antigene quantity. It is shown that the course of the reaction essentially depends on the duration of delay. Parameters regions corresponding to different regimes are determined.     

Effect of combined preventive use of quadevit with antibiotics on the survival and humoral immune response in experimental studies]

An attempt to correct with quadevit immunodepression due to prophylactic administration of benzylpenicillin and gentamicin for 6 days provided positive results. There was a significant increase in the quantities of Ig 19S and Ig 7S after the animal immunization with the bacterial antigen, an increase in the number of the AFCs in the spleen of the albino mice in response to administration of sheep erythrocytes and an increase in the survival rate of the animals with salmonellosis. The simultaneous use of quadevit with cefamezine and erythromycin did not lower the unfavourable influence of the antibiotics on the immune status of the animals.