Leukoplakia of oral mucosa: pathogenesis and possible correction with phytoadaptogen.

Leukoplakia of the oral mucosa is characterized by impairment of the epithelial differentiation program. The use of complex phytoadaptogen in the treatment of patients with leukoplakia normalized expression of Fas-APO-1 antigen and keratin 17; increased expression of CD54 attested to activation of immune effectors. The clinical effect manifested in involution or shrinkage and loosening of the pathological focus and complete epithelialization of erosive surfaces. The phytopreparation exhibited adaptogenic effects normalizing the immune and IFN status and improving the state of adaptation systems in the body.

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.

[The use of cycloferon in the therapy of experimental herpetic keratitis]. / Ispol'zovanie tsikloferona v terapii éksperimental'nogo gerpeticheskogo keratita.

The cycloferon efficacy was investigated in the treatment of experimental herpesvirus kerato-conjunctivitis in rabbits. The model was demonstrated to reflect the main aspects of herpesvirus eye lesions in humans. Cycloferon application similarly to that of known interferon inducer poludan has been shown to enhance processes of inflammation and subsequent regeneration of eye tissues as well as to decrease mortality of animals due to the generalization of infection.

[The radioprotective and interferonogenic properties of influenza vaccine]. / Radioprotektivnye i interferonogennye svoistva grippoznoi vaktsiny.

Different methods of prophylactic treatment with influenza virus vaccine increase survival of irradiated mice and hamsters by 25-55% as compared to unprotected ones. Higher radioresistance occurs in the same time intervals as a rise of interferon in the blood after immunization with influenza virus vaccine.

[The effect of exogenous interferon on the in vitro production of alpha- and gamma-interferon by the lymphocytes of patients with respiratory papillomatosis]. / Vliianie ékzogennogo interferona na produktsiiu al'fa- i gamma-interferona in vitro limfotsitami bol'nykh respiratornym papillomatozom.

The influence of various interferon concentrations in vitro on alpha- and gamma-interferon production by lymphocytes of children suffering from respiratory papillomatosis was studied for optimization of interferon therapy. Most of the children with clinical improvement after interferon treatment showed proportional dependence of alpha-interferon production upon exogenous interferon concentrations and stability of gamma-interferon production. In children without clinical improvement, initial production of both interferons was reduced significantly in the absence of IF in the medium, but no changes occurred when exogenous interferon was present in the medium. The test proposed here may be used for the determination of patients' sensitivity to interferon and for individualization of interferon treatment schedules in other long-lasting recurrent diseases.

[The antiviral activity of amiksin and its effect on the interferon status in hepatitis in mice]. / Protivovirusnaia aktivnost' amiksina i ego vliianie na interferonovyi status pri gepatitie myshei.

A single administration of amixin followed by oral infection with mouse hepatitis virus provided protection of 40%-50% animals for 72 hours and normalized the interferon status. In parallel with decreasing level of virus-induced endogenous interferon the interferon-inhibiting activity of lymphocytes of the infected animals increased and approached normal levels.

[Antiviral activity of amiksin incorporated into liposomes]. / Protivovirusnaia aktivnost' amiksina, zakliuchennogo v liposomy.

The results of a comparative study of the antiviral activity of amyxin (tilorone) without liposomes and incorporated into liposomes on the model of experimental enteral hepatitis of mice are presented. The use of amyxin in liposomes was shown to prolong interferon production and to provide significant 60% protection of the animals. The possible mechanism of increasing the antiviral effectiveness of amyxin upon its incorporation into liposomes, enteral administration and subsequent enteral infection of mice with hepatitis virus is discussed. It is assumed that use of amyxin in liposomes may increase its effectiveness in prevention of human hepatitis A.

[Effect of low-molecular interferon inducers in experimental hepatitis in mice]. / Effekt nizkomolekuliarnykh induktorov interferona pri éksperimental'nom gepatite myshei.

Among low molecular interferon inducers preparations were selected which were capable of inducing interferon (IFN) synthesis after oral administration and advantageous for further clinical use. The dynamics of interferon production was studied after oral administration of three national low molecular interferon inducers. The selected preparations: a synthetic inducer, amiksin, and 2 natural compounds (gossypol derivatives), kagocel-1 and PXL-6, stimulated high levels of interferon production (from 10,000 to 20,000 IU/ml) in the intestinal tract of the animals 4 hours after induction and protected the animals from hepatitis virus of mice (the Meshcherin strain) after oral administration 24 hours before infection (35-55%). Amiksin and PXL-6 produced significant protection (p less than 0.01 or 0.001)--40 or 50%, respectively, when administered 4 hours before virus infection.

[Interferon and other immunological indices of influenza patients undergoing different methods of treatment]. / Interferon i drugie immunologicheskie pokazateli u bol'nykh grippom pri raznykh metodakh lecheniia.

The authors review the results of immunological examinations of patients with influenza given adapromine and virazole drugs as well as reflex therapy aimed at increasing general host resistance. Patients with influenza administered reflex therapy among other therapeutic measures developed more intensive increase of serum interferon activity in the acute period of the disease, with its more rapid decline; they had a high level of IgM and more intensive rise of specific antibody (in the HI test) as compared with the control group. In the group of patients treated with adapromine and virazole there was also a more significant increase of IgM level, early and significantly high level of IgG as compared with the patients given symptomatic drugs. No differences in the number of T-lymphocytes were found by the method of spontaneous rosette formation with sheep erythrocytes. Both in treatment with antiviral drugs and using reflex therapy, a more rapid disappearance of influenza antigen from nasal smears was observed than in patients of the control groups.

[Interferon-inducing and antiviral activity of maleic anhydride copolymers]. / Interferonindutsiruiushchaia i protivovirusnaia aktivnost' sopolimerov maleinovogo angidrida.

Data on synthesis of new polymer compounds with potential interferon-inducing and antiviral activity are presented. Maleic anhydride (MA)-based alternating copolymers, in particular, copolymers of divinyl ether with MA containing five-member oxygen cycles in the chain, as well as furan copolymers with MA, were shown to be promising interferon inducers. The antiviral activity was found in copolymers based on allene hydrocarbons.

[Effectiveness of interferon inducers in experimental influenza]. / Effektivnost' induktorov interferona pri éksperimental'nom grippe.

Certain high and low molecular interferon inducers poly(I), poly(C), polyguacyl, RFf2, dsRNA, tiloron) possess a marked antiinfluenza effect. The level of protection of the infected animals reached 70-80% under optimal condition of the use of the inducers. There was a clear-cut correlation between titres of serum interferon and the animal survival rate.

[Interferon-inducing and antiviral activity of dsRNA of yeast origin]. / Interferonindutsiruiushchaia i protivovirusnaia aktivnost' dsRNK drozhzhevogo proiskhozhdeniia.

The paper describes derivation of double-stranded RNA from K plasmid of Sachcaromyces cerevisiae yeast by means of electrophoresis in agar gel and by differential salting out with 4 M lithium chloride. Studies in vitro and in vivo demonstrated a high interferon-inducing and antiviral activity of dsRNA preparations from the yeast plasmid.

[Properties of double-stranded RNA as an interferon inducer]. / Svoistva dvuspiral'noi RNK kak induktora interferona.

The stability and activity of double-stranded RNA (dsRNA) preparations as interferon inductors were studied. They were found to be stable upon long storage and ultrasonic treatment for aerosol preparation. Data on dsRNA toxicity for mice and rabbits are presented. The kinetics of interferon production and its distribution in tissues in relation to the routes of inoculation were studied. Investigation of dsRNA antiviral activity in various experimental viral infections demonstrated a protective effect of the preparation after a single prophylactic administration of the inductor.