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Biomedical subjects

E B Tazulakhova

Publications and source records attributed to E B Tazulakhova.

At least 19 recordsLinked to original sources
PubMed2001

Russian experience in screening, analysis, and clinical application of novel interferon inducers.

This review describes a long-standing experience of screening for interferon (IFN) inducers in Russia. IFN inducers represent a special group of potential antiviral compounds. The main requirements for them are (1) high IFN-inducing activity, (2) absence of side effects, (3) wide spectrum of antimicrobial activity, (4) broad therapeutic security and, (5) good solubility in water and biologic liquids. IFN inducers stimulate IFN production in different cells and organs, and that determines the strategy for their application. Amixin (OOO "Lancepharm," Moscow, Russia) induces IFN-alpha/beta production mostly in T cells. Cycloferon (NTFF "Polysan," St. Petersburg, Russia) stimulates B cells and macrophages to produce almost pure IFN-alpha. Double-stranded RNA (dsRNA) and polyphenols of natural origin stimulate IFN production in different populations of immunocytes. Only polymers, such as Larifan (Riga, Latvia), Kagocel ("NIARnedicplus," Moscow, Russia), and Ragosin (N.F. Gamaleya Institute, Moscow, Russia), induce IFN synthesis in muscles, so they may be effective against rabies. Cycloferon, Larifan, and Kagocel, which induce IFN formation in lungs, may be effective against influenza and rhinoviral infections. Cycloferon and Larifan stimulate IFN production in liver and spleen and may be effective against hepatitis B. Oral compounds (Amixin, Kagocel) that stimulate IFN production in intestines may be effective against hepatitis A and enteroviral infections. Low molecular weight inducers (Amixin, Cycloferon, Kagocel) that penetrate the blood-brain barrier may be active against viral encephalitis. At present, clinical trials of IFN inducers are limited, but in the near future, IFN inducers may be used against very different infections and conditions.

Animals↗
PubMed1999

[Interferon inducers: new generation of immunomodulators].

Interferon (IFN) inducers are the agents having a wide range of antiviral activity. They have not only etiotropic, but marked immunomodulating effects. INF inducers different in its nature cause IFN synthesis in different immunocytic populations. The kinetics of the production of IFN and their antigenic composition depend on the chemical structure of an inducer and on their stimulated target cell populations. Their capacity of stimulating the synthesis of IFN in these or those organs determines the spectrum of application of an inducer and the time course of serum IFN accumulation--the strategy of its use. IFN inducers have a number of advantages over exogenous IFN. They stimulate the synthesis of the body's own IFN, which has no antigenicity unlike the most widely used recombinant IFN. IFN inducers cause IFN circulation at the therapeutical levels, at the same time to achieve such an effect requires multiple administration of large-dose exogenous agents. Some IFN inducers includes IFN synthesis in particular cell populations and organs, which has certain advantages over the polyclonal stimulation of IFN immunocytes. IFN inducers are well combined with IFN and other antiviral agents. The combination of these properties leads to the conclusion that IFN inducers are a highly promising group of agents having both etiotropic and immunomodulating effects.

Adjuvants, Immunologic↗
PubMed1999

[Para-aminobenzoic acid--an interferon inducer].

Para-aminobenzoic acid (PABA) was shown to be an early type interferon inductor. PABA (10 micrograms/ml) induced interferon production in vitro in the cells of human peripheral blood and in vivo in albino mice (10 mg/kg). The results of the study suggested that PABA was able to induce production of interferon-alpha/beta in various immunocyte populations. By its interferonogenic activity PABA was comparable with the known interferon inductors. One of the mechanisms of the previously described in vivo antiherpes action of PABA can be attributed to its interferon inducing activity.

4-Aminobenzoic Acid↗
PubMed1992

[Combined experimental use of vaccine against acute human encephalomyelitis and immunomodulators].

Combined use of vaccine and immunomodulators such as ridostin, inosiplex and polyribonate against acute encephalomyelitis of humans (AEMHs) was studied. It was shown that low immunogenic doses of the vaccine did not provide a protective action against the virus of AEMHs while after administration of the vaccine in combination with the immunomodulators there was protection in all the groups of the animals exposed to the low immunogenic doses of the vaccine during the first immunization. It was noted in regard to all the combinations of the immunomodulators and vaccine used in the low immunogenic doses that the level of the increase in the titer of the virus-specific antibodies, the proliferative activity to the specific antigen and mitogens and of interferon induction depended on the immunomodulator type. At the same time, it was found that the marked production of interferon within the first 24 hours observed after the use of the combination of inosiplex, ridostin and the vaccine resulted in increased activity of natural killer cells and lower proliferative activity of cells and production of virus-specific antibodies. This was indicative of the necessity of choosing the immunomodulators, their doses and time of the administration in relation to the immunization.

Acute Disease↗
PubMed1992

[Interferon-inducing activity of hydroxybenzylamine derivative].

Interferon-inducing activity of the interferon inductor savrats, an oxybenzylamine derivative of was studied. It was shown on experimental animals that along with its low toxicity, savrats had a high interferon inducing capacity. There were early and late peaks of interferon production (4-8 and 48-96 hours later, respectively) depending on the route of the inductor administration. It was noted that for optimization of the schemes for using interferon inductors, careful choosing of the drug pairs participating in the induction and employment of various routes for administration of the same drug are required.

Administration, Oral↗
PubMed1992

[Pharmacokinetics of the interferon inducer PHL-6 and interferon synthesis in target organs under various methods of drug administration].

The pharmacokinetics of PHL-6 and interferon synthesis dynamic in the target organs (tissues) of mice were studied during its and intraperitoneal administration. In the experimental setting, there was a direct correlation between the interferon production in the murine organs with single PHL-6 and distribution of 14C PHL-6. The highest radioactivity with its oral administration was detected in the liver and intestine. Interferon was actively synthesized in the intestine, liver and serum, showing the levels of 20000, 1024-2048 and 512-1024 IU/ml, respectively. The prolonged action of the drug was in good agreement with the low PHL-6 excretion from the body. It was also shown that almost the whole radiation dose 1 (greater than 98%) was excreted with feces and urine after single and chronic administrations of uniformly labeled PHL-6 which proved important clinical drug use.

Administration, Oral↗
PubMed1991

[The role of immunocytes in the production of interferon in response to its induction by aromatic hydrocarbons].

Interferon (IF) was synthesized in animals by diverse populations of immunocytes in response to induction by various low molecular weight aromatic hydrocarbons. The level of the involvement of either population of the immunocytes in IF production is determined by the chosen inductor. IF induction by acridanone L-1 was mainly observed in macrophages and B-lymphocytes. T-Cells actively participated in IF synthesis induced by amyxin, a representative of the fluorenone group. IF synthesized by lymphocytes of human peripheral blood in response to L-1 was completely neutralized by antiserum to alpha-IF while IF induced by amyxin in the same culture was a mixture of alpha- and beta-IFs at a ratio of 3:1.

Acridines↗
PubMed1990

[Inhibition of Chlamydia trachomatis multiplication by interferon inducer larifan in mice with experimental infection].

Interferon (IF)-inducing capacity of C. trachomatis was shown in experiments on mice CBA. The levels of IF production in the parenchymatous organs correlated with accumulation of the pathogen in them. The use of larifan, a natural double-stranded IF inductor, according to the treatment scheme provided high levels of endogenic IF in infected mice. It inhibited multiplication of Chlamydiae in the lungs and lymph nodes detected cytoscopically by light and fluorescence microscopy and with infection titration. The effect of the inductor combined with tetracycline was of additive nature. Double intraperitoneal administration of larifan with an account of the hyporeactivity phase and daily administration of tetracycline proved to be the most efficient. It is possible to successfully use IF inductors in accordance with the treatment schemes in infection caused by C. trachomatis which makes promising their clinical application in therapy of chlamydiosis.

Animals↗
PubMed1990

[Role of macrophages in interferon production].

The role of macrophages in production of interferons (IF) is manysided. They are able to synthesize IFs after any induction. However, the function of macrophages as producers of IFs is not, probably, basic. The levels of IFs produced by them are mainly low. When they are stimulated by inducers of "early" IF the synthesis is performed by intact macrophages whereas with the use of inducers of "late" IF there is always observed joint activity of macrophages and other immunocompetent cells. The main role of macrophages in production of IFs is in regulation of synthesis of these proteins in the host. In addition, they are able to serve as stimulating cells in inducing IF production by the majority of drugs by transmitting information on IF synthesis to lymphocytes. This function of macrophages is not species-specific.

Animals↗
PubMed1989

[Immunomodulating properties of interferon inducers].

Data on the immunomodulating activity of interferon inductors are presented. It was revealed that the inductors increased the animal vaccinal response. Schemes for combined use of the interferon inductors and immunomodulators were developed. The immunomodulators were shown to increase the host interferon response evident from synergistic increasing of the interferon titers or prolongation of interferon circulation in blood of the animals. The efficiency of the schemes for combined use of the interferon inductors and immunomodulators was obvious from stimulation of the antibody production. As a result the time of the antibody circulation in blood increased. The effect of the combined use of the immunomodulators and interferon inductors was studied. The combined use of the preparations significantly increased the average life-span of the animals and the rate of their survival.

Animals↗
PubMed1988

[Effect of calcium chloride on interferon production and the biosynthesis of cellular macromolecules].

The influence of calcium chloride in production of interferon and biosynthesis of cell proteins, RNA and DNA in the cultures of chick embryo fibroblast cells and murine cells L-929 in response to induction of the cells by poly(I).poly(C) was studied. It was shown that calcium ions in concentrations of 10 to 30 mM markedly increased formation of interferon in the cell cultures.

Animals↗
PubMed1985

[Interferon-inducing and antiviral effects of inosiplex in combination with high-molecular interferon inducers].

It has been shown that the immunostimulant inosiplex (IP) is capable of inducing interferon production in mice and of stimulating interferon induction by high-molecular inducers. The combined use of IP and poly (G)-poly (C) or dsRNA (RFf2) leads to a longer interferon circulation in the blood. All the combination schemes ensuring the effect of interferon production prolongation were tested for anti-viral activity. The prophylactic administration of the drugs permitted the attainment in mice of the increased resistance to experimental influenza.

Animals↗
PubMed1985

[Interferon-inducing activity of a tilorone hydrochloride preparation].

The experiments on CBA mice showed that tyloron hydrochloride was an active inductor of interferon. The maximum production of interferon in blood (2560 units/ml) was achieved with oral administration of tyloron in a dose of 400 mg/kg. It was demonstrated that the character of interferon accumulation in different organs depended on the route of tyloron administration. When the inductor was administered orally, the highest levels of interferon were observed in the intestine (5000 units/g) and blood (320-640 units/ml). When the inductor was injected intraperitoneally, significant levels of interferon were detected in the animal brain (at least 5000 units/g). After intramuscular injection of the inductor insignificant levels of interferon were practically detected in all the organs. Participation of the brain cells and blood elements in production of interferon is discussed.

Animals↗
PubMed1985

[The state of hyporeactivity in interferon production: localization and partial purification of the factor repressing the interferon production].

The hyporeactivity factor in interferon production by L-929 cells designated IRP (interferon repressing protein) has been studied. In particular, its localization and methods of its purification have been studied. The kinetics of IRP accumulation by producing cells correlate with the development of hyporeactivity condition. Most of IRP is localized in cell sap and in ribosomal fraction in evidence to regulatory role of repressor at the level of interferon mRNA translation. A 100-fold increase in repressor activity was achieved by IRP concentration by ammonium sulfate precipitation. IRP as well as interferon have been shown to possess high affinity to polyU sepharose. The preparations of IRP and interferon concentrated by ammonium sulfate precipitation were subsequently purified by fractioning in a polyI sepharose column. A 10,000-fold (6 x 10(4) U/mg) purification was achieved for IRP and 250-fold (10(4) U/mg) for interferon.

Animals↗
PubMed1985

[Effect of the combined use of dextran sulfate and double-stranded RNA on interferon production].

The studies were performed on CBA mice. It was shown that polynucleotide inductors (poly I-poly C, RFf2 and poly G-poly C) stimulated production of interferon with a peak attained 4-6 or 24 hours after the induction. Intraperitoneal injection of dextran sulfate in a dose of 200 micrograms/m induced production of interferon in small amounts (80-120 units). The production peak was observed in 12 hours. The combined use of dextran sulfate and the polynucleotide inductors provoked an increase in the interferon production. The effect was of a synergistic nature. The cells of the immunocompetent system were the target of the dextran sulfate effect in the host, which was shown experimentally with a culture of mouse lymphocytes.

Animals↗
PubMed1983

Regulation of interferon production. Superinduction by dihydrorifampicin in human and chick embryo fibroblasts and mouse L929 cells.

Dihydrorifampicin (DHR), a new reversible inhibitor of RNA polymerases I and II in eukaryotic cells, exhibited a very high enhancing effect on the production of interferon (IFN) in cultures of human and chick embryo fibroblasts and mouse L929 cells induced by poly(I). poly(C). The titres of interferon produced in human fibroblast cultures superinduced with poly(I). poly(C), cycloheximide and DHR were 128 times higher as compared with cultures treated with poly(I). poly(C) only. A similar superinduction of interferon by DHR was observed in mouse and chicken cell cultures, IFN titres in culture media were 40-60 times higher in comparison with cultures treated only with the inducer. In comparison with actinomycin D in the superinduction experiments, DHR was not toxic and allowed much higher yields of IFN. The use of DHR may be especially advantageous for the superinduction and production of human fibroblast IFN in cultures of human diploid fibroblasts.

Animals↗
PubMed1983

[Interferon production by different inducers].

The rates and time course of interferon production in mice administered nine inductors of different nature were studied and compared. Use was made of the most prospective synthetic and natural polymers as well as of low-molecular preparations. It was established that polymers bring about early interferon production with a peak being reached in 4-6 hours, followed by rapid disappearance. Low-molecular inductors are marked by late interferon production, with the maximal titers attained in 24-48 hours, followed by prolonged circulation (4 days of observation).

Animals↗