Different effects of the immunostimulatory drug Stimforte on infections of hepatitis C virus and herpes simplex virus type 1.

Stimforte, an immune response-stimulating preparation, is active with respect to hepatitis C virus (HCV) and herpes simplex virus type I (HSV-1). The effects of Stimforte in animals infected with either HCV or HSV-1 are fundamentally different. In mice with acute herpes virus infection, Stimforte administration leads to a higher activity of natural killer cells and cytotoxic lymphocytes, and the amount of interferon (IFN) λ grows. In mice infected with HCV, Stimforte administration results in a significant increase in IFN-ß but not IFN-λ in blood and affected organs. Stimforte has been found to affect directly HCV reproduction that causes the infected cell death, but it does not affect HSV-1 reproduction in the Vero cells (V).

[Interferon inductor activity and interferon production under the action of acridonacetic acid salts].

Peculiarities of the kinetics of accumulation and duration of circulation of three types of interferon under the action of acridonacetic acid salts have been studied. Optimum doses of meglumine salt of acridonacetic acid are established, which ensure efficient and consistent induction of three interferon types, ensuring their prolonged circulation in the blood.

[Substances from pyrolised tissues of reptile carcases differently modulate immunity of mammals of both sexes].

Substances with gender action on immunity were detected in water soluble hydrolised matter from reptile carcases. The gender action was shown on isolated blood neutrophils, whole blood and in vivo by the antiviral activity on experimental animals, contaminated with three types of viruses: Herpes simplex type 1, the virus of encephalomyocarditis and the virus of hepatitis of mice. The possible mechanism of the inhibitory action on the male immunity was associated with the protein kinase cascade, including protein kinase C, activated by phorbolmyristate in the cells of the immune system.

[Cycloferon in therapy of hyperplastic laryngitis for decrease of the number of relapses].

The article describes the clinical forms of chronic hyperplastic laryngitis, characterized by persistent and recurrent course, a tendency to the formation of oncological pathology, at the expense of hyperplastic changes in the larynx, leading to a malignancy of the inflammatory process. It was demonstrated the bacterization of larynx by Epstein-Barr virus (EBV) and Mycoplasma in imbalance of system of interferon. Clinical recovery, depending on the clinical form of the disease, using cycloferon, was observed in 57.4% of patients. The inclusion in the complex of the medical support of chronic hyperplastic laryngitis inducer of interferon - cycloferon, provided the reduction of the number of relapses.

[Cycloferon in complex therapy management of chronic laryngitis].

The clinical course of various forms of chronic laryngitis, including contact granulomas not only persistant and relapsing, but also inclined to oncologic pathology due to hyperplastic changes in the larynx resulting in malignization was described. Inhibition of the leukocyte interferon-synthesizing activity was observed in more than 88.1% of the subjects. Pathogenic viruses were isolated from 48.2% of the patients, EBV and mycoplasma prevailing. High direct correlation between chronic laryngitis and Herpes viruses was shown. The presence of three-component virus associations in the larynx mucosa was likely indicative of the bening process malignancy. The use of the interferon inductor cycloferon in the complex surgical and medicamentous management of chronic laryngitis was shown valid. The rate of the relapses lowered to 1.7 episodes a year.

[Cycloferon as an agent for the anti-relapse therapy in patients with chronic hyperplastic sinusitis].

The data on the efficacy of cycloferon as an agents of antirelapsing therapy in management of 123 patients with chronic hyperplastic sinusitis are presented. The drug induction of endogenous interferons was validated by the properties of the local mucosal immunity, virus invasion and virus persistence in the nasal an d accessory nasal sinuses mucosa, as well as by different levels ofthe interferon production deficiency. The clinical efficacy was stated in 53% of the cases. The relapses were recorded in 13.1% of the patients treated with cycloferon vs. 33.3% of the patients under the local corticosteroid therapy.

[Up-to-date approach to treatment of inflammatory infections in the maxillofacial region].

Cycloferon, a prospective interferon inductor, and the mechanism of its action were characterized. Its formulation for external use as liniment was developed. The pharmacotherapeutic effect of the drug in the treatment of paradontitis was shown. The drug efficacy in herpetic lesions of the mouth and lips mucosa was observed. The use of cycloferon in the treatment of the buccal mucosa affections in HIV-infected subjects was substantiated.

[The mechanism of stimforte action on herpesvirus infection.]

Increased protease activity and a significant amount of granzyme B were observed in in organs of mice infected with acute herpes simplex virus HSV-1 with the introduction of Stimforte (100 or 250 µg/mouse). Thus, this drug activates killer cells, which play an extremely important role in the suppression of HSV-1 infection. Although the administration of Stimforte (100 µg/mouse) to intact mice results in the activation of IFN-ß production and does not activate the production of IFN-λ, Stimforte administration to animals infected with HSV-1 reduces production of IFN-ß in serum, brain and lungs, whereas the production of IFN-λ considerably increases as the result of administration of 100 µg/mouse of Stimforte.

[The action of high-molecular linear polymers on the circulatory system]. / Vozdeistvie vysokomolekuliarnykh lineinykh polimerov na sistemu krovoobrashcheniia.

An analysis of the hemodynamic consequences of the injections of long linear polymers with high molecular weight is introduced. These injections lead to an increase of the cardiac output, to a decrease of the blood pressure, and hence cause a reduction of the resistance to blood flow. It follows that such kind of polymers is able to normalize hemodynamics under some pathophysiological conditions, e.g., during experimental atherosclerosis, ischemic state, hemorrhagic shock. An addition of drag-reducing polymers into the blood system is associated with a modification of the blood flow microstructure itself.

[Vasodilators as interferon inducers]. / Vazodilatatory kak induktory interferona.

Vasodilating drugs, inhibitors of cAMP phosphodiesterase activity (theophylline, caffeine, theobromine, etc.) and other vascular drugs (papaverin, dibasol, no-spa, etc.) were found in experiments in vivo to be capable of inducing interferon the peak of whose production was determined in the blood of animals 24 hours after drug administration (the observation period). The interferon production is critically dependent upon the dose and routes of administration of the drugs. The interferon induced by vasodilating drugs belongs to interferon of the 1st species. It is assumed that both endothelial cells of vessel walls and lymphocytes may take part in interferon production.

[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.

[Interferon-inducing activity of liposome-incorporated double-stranded polynucleotides and the means for its enhancement]. / Interferonindutsiruiushchaia aktivnost' zakliuchennykh v liposomy dvuspiral'nykh polinukleotidov i puti ee povysheniia.

Natural double-stranded RNA (dsRNA) incorporated into liposomes upon parenteral inoculation induces 4 times as much amounts of interferon as inoculation of the equal amount of dsRNA without liposomes. Oral administration of liposome-incorporated dsRNA induces in animals serum interferon in amounts similar to those induced by parenteral inoculation of dsRNA without liposomes (320-640 units/ml). When liposome-incorporated dsRNA is used, interferon induction is prolonged to 24 hours. The prolongation period increases to 5 days after preliminary treatment of animals with "empty" liposomes. In M-19 cell culture, 2-hour treatment with liposome-incorporated dsRNA in a dose of 5-10 micrograms/ml induces a yield of 640-1280 units/ml interferon and 100% antiviral effect. The L-929 culture is more sensitive to dsRNA in liposomes. Even its minimal amounts (0.1-1 microgram/ml) after 2-3-hour contact produce a 100% antiviral effect in the presence of low amounts of interferon in the culture fluid (20-40 units/ml) or in its complete absence.

[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.

[Disordered interferon status in patients with urticaria and angioneurotic edema against a background of frequent ARVI: its correction with reaferon]. / Narushenie interferonovogo statusa u bol'nykh krapivnitsei i angionevroticheskimi otekami na fone chastykh ORVI: korrektsiia reaferonom.

The results of clinical, allergological, virological, and immunological examinations of patients with urticaria and angioneurotic edema against the background of frequent ARVI are presented. Disorders in the interferon system in these patients were studied. A positive anti-recurrent effect of prophylactic parenteral course of a national recombinant alpha 2-interferon (reaferon) in this pathology has been demonstrated.

[The influence of examination stress on psychophysiological characteristics and heart rate in students]. / Vliianie ékzamenatsionnogo stressa na psikhofiziologicheskie pokazateli i ritm serdtsa studentov.

With the aim to assess the influence of pre-examination psychoemotional stress on the level of centralization of the heart rate control, mathematical analysis of ECG of students was performed in normal condition (a common day of academic semester), before, and after an examination. The ECG was recorded and processed with the help of IBM-486 PC. R-R cardiointevalograms were processed by the method of variational pulsometry after Baevsky. Common quantitative heart rate indices were studied. The level of anxiety of students was assessed by Spilberger, and subjective estimations of general condition, activity and mood were obtained from the respective questionnaire. Three types of heart rate reactions on the examination stress were revealed. The reactions depended on the individual typological characteristics and the state of autonomic nervous system.

[Evaluation of the interferon status of human subjects by whole-blood specimens]. / Otsenka interferonovogo statusa liudei po probam tsel'noi krovi.

A simple method for the determination of three parameters of human interferon status: serum interferon (IFN) and induction of alpha- and gamma-IFN in specimens of 10-fold-diluted whole blood in a volume of 200 microliters is described. Standard parameters of interferon status of normal subjects in the whole blood are given which can be visually presented as a triangle of interferon status, and its deviations in various pathological conditions. The whole-blood method is recommended for large-scale clinical surveys, especially in pediatrics.

[Characteristics of interferon production from the enteral administration of inducers]. / Osobennosti produktsii interferona pri énteral'nom vvedenii induktorov.

When interferon inducers are administered to animals, autonomous local production of interferon by organs (intestine, liver) occurs alongside with the production of serum interferon. After oral administration of a low molecular interferon inducer, tilorone, the intestine is the main site of interferon synthesis. Here the peak of interferon production precedes that in the serum by 20 hours and exceeds it 16-fold. The sequence of events follows the scheme: intestine--liver--serum. Upon oral administration of high molecular inducers incorporated into liposomes (polyguacyl, lafarin) the predominant site of interferon production is the liver where over 80% of the administered inducer is localized and interferon production is 2-4-fold higher than in the intestine. The sequence of events follows the scheme: liver--intestine--serum.

[Influenza virus sensitivity to interferon and its inducer]. / Chuvstvitel'nost' virusov grippa k interferonu i ego induktoru.

The results of the study on influenza virus sensitivity to interferon of two kinds (human and chicken) and its inducer, poly(G) . poly(C) are presented. Differences in this characteristic among human and animal influenza viruses were demonstrated. There was a correlation between sensitivity to poly(G) . poly(C)-induced interferon and sensitivity to chicken interferon. Comparative studies of sensitivity to interferon in parent viruses and recombinants demonstrated that recombinants derived this property from one of the parental strains.

[Trial of polyguacyl safety and tolerance]. / Ispytanie bezvrednosti i perenosimosti poliguatsila.

The results of studies of the antiviral and interferon-inducing activity of the synthetic interferon inducer polyguacyl in white mice as well as the results of the study of safety and tolerance of this drug given to human subjects as aerosol and intranasally are presented. Both modes of administration to mice induced production of endogenous interferon, although after intranasal inoculation high interferon titres in the blood serum of the animals were observed for longer periods of time, whereas after aerosol administration interferon disappeared more rapidly. Significant antiviral protection was achieved only by the intranasal administration of the inducer resulting in 84.0% survival of the animals challenged with the mouse-adapted influenza A/Aichi virus. Clinical trials of polyguacyl in human volunteers demonstrated the safety and good tolerance of this drug given both as aerosol and intranasally.