[Antiviral activity of the organic germanium complex with aciclovir against herpes simplex virus (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1/2) in the in vitro and in vivo systems].

INTRODUCTION: A significant increase in the incidence of various forms of herpesvirus infection (HVI) determines the need to search for new approaches to the modification of one of the basic antiviral drugs aciclovir (ACV) and its dosage forms to improve their biopharmaceutical characteristics and increase the effectiveness of therapy. In this aspect, an innovative organic germanium complex with aciclovir (OGCA) is promising.The aim of the study was to assess the antiviral activity of OGCA against the herpes simplex virus (HSV) (human herpes virus, HHV) on the HVI models both in vitro and in vivo. MATERIAL AND METHODS: We studied the activity of OGCA in a therapeutic regimen against HSV-1 (HHV-1) (Kl strain), HSV-2 (HHV-2) (VN strain) using virological and statistical research methods in the in vitro model of HVI on Vero cell culture and the model of genital herpes (GH) caused by HHV-2 (VN strain) in male guinea pigs (Canis porcellus). RESULTS AND DISCUSSION: It was found OGCA inhibits the replication of HHV-1 and HHV-2 in Vero cells, and has anti-HHV activity in the GH model in male guinea pigs, leading to a decrease in the severity and duration of the disease, the intensity and duration of viral shedding. The most pronounced activity was detected when preparation was applied topically 5 times a day for 5 days at the early stages of infection (3% gel). The delayed use of OGCA (48 hours after infection) also had statistically significant efficacy compared to commercial reference drugs containing aciclovir or its pro-drugs: aciclovir (5% cream), AIL (acyclovir+interferon alfa-2b+lidocaine, 3% ointment), penciclovir (1% cream). OGCA significantly reduced the number of days of the pathogen shedding, as well as its infectivity, compared to animals in the control group and ones receiving placebo. The activity of OGCA, apparently, is due to its improved biopharmaceutical characteristics compared to aciclovir, as well as the presence of a number of biological activities of its constituent components. CONCLUSION: The results of the study allow us to consider OGCA as the basis for the development of antiviral agents for the treatment of HVI.

Physiological parameters of Macaca fascicularis immunized with anti-rubella vaccine with germanium-based adjuvants.

Clinical status, hematological and biochemical parameters, and allergenic activity of organogermanium compounds used as adjuvants in complex with preparation from Orlov rubella virus vaccine strain and reference commercial anti-rubella vaccine based on Wistar RA 27/3 strain were studied on Macaca fascilcularis of both genders. Physiological parameters of monkeys immunized with the Russian and foreign rubella virus vaccine strains with and without adjuvants did not differ. The adjuvants were inessential for the safety of vaccines (absence of toxicity, reactogenic activity, or allergenic activity) in preclinical studies on lower primates.

[Activating effect of a germanium-organic compound on immunocompetent cells during intranasal immunization of mice with a live influenza vaccine].

AIM: Detailed characteristic of results of intranasal immunization of mice with one of two variants of vaccinating influenza virus, particularly in combination with a low molecular weight germanium-organic compound (LMW-GOC). An additional aim is evaluation of effect of LMW-GOC on the parameters of immune system in case of intranasal administration of the preparation without the addition of vaccinating virus. MATERIALS AND METHODS: The study was carried out in female CBA mice (18-20 g, 6 animals per group). Intranasal immunization was carried out by 2 different variants of B/Victoria influenza virus--once or twice with a 2 week interval. Cells for study were obtained from spleen and nasal- and bronchial-associated lymphoid tissue (NALT/ BALT) 24 hours and 7 days after intranasal administration of the preparations. The main method of the study--determination of the level of expression of various markers oflymphocytes in comparison with the level of the same markers in the cells of control group animals by using flow cytometry method. The mean parameters obtained were determined by using program package WinMDI 2.8. RESULTS: The main results were the increase of level of expression of various lymphocyte markers obtained from mice after intranasal administration of the vaccines and their combination with LMW-GOC or LMW-GOC only without the participation of the vaccines. A significant increase of the expression of TLR9 marker compared with other parameters was noted. Administration to mice of wild B/Victoria strain notably more frequently conditioned the decrease of expression of some parameters compared with administration of the cold adapted strain. Effect of LMW-GOC without the vaccine also conditioned the increase of levels of markers however a combination of the preparations with the vaccine was more effective. CONCLUSION: The increase of level of expression of a number of lymphocyte markers may serve as a sign of successful intranasal vaccination against influenza. LMW-GOC preparation increases immune stimulating effect of intranasally administered vaccines and in none of the cases weakens the stimulating result of effect of the vaccines, and in many cases increases it. LMW-GOC may be studied as a main or additional adjuvant for intranasal application of influenza vaccines.

[Activation of lymphocytes under the influence of an influenza vaccine combined with a low molecular weight germanium organic compound].

AIM: Confirmation of immunostimulating effect of an original low molecular weight germanium organic compound (LMW-GOC) during immunization of mice with Vaxigrip vaccine. MATERIALS AND METHODS: The experiments were carried out in CBA mice divided into 4 groups: control, those that received Vaxigrip influenza vaccine intraperitoneally, those that received LMW-GOC intraperitoneally and those that received both preparations at once. Effect of the preparations administered was evaluated by flow cytofluorometry based on changes of CD3, CD4, CD5, CD8, CD19, CD25, Foxp3, NK1.1, gammadelta T, MHC II, TLR2, TLR4, TLR9 expressing cell content in mice spleens. The content of the colored cells was determined at normal, 24 hours and 7 days after the administration of the preparations. Statistical treatment of the data was carried out by using Win MD 128 program package. RESULTS: LMW-GOC can enhance the effect of Vaxigrip vaccine that is expressed by an increase of content in spleen of some lymphocyte subpopulations 24 hours and 7 days after the intraperitoneal administration. In some cases LMW-GOC increases the content of some lymphocyte subpopulations in mice spleen after administration as a monopreparation, i.e. without the vaccine. LMW-GOC suppressed stimulating effect of the vaccine on the spleen content of various lymphocyte subpopulations in none of the observations. CONCLUSION: By using cytofluorometry method it is possible to form an understanding of an elevated role of various types of cells in the development of immune response to the vaccine as well as regarding additional enhancement of this response during administration of LMW-GOC to mice. The effect of the preparation is manifested for a few days after its administration. The preparation manifests adjuvant properties and after further studies may be suggested for use as an adjuvant.

[Immunoenzyme test system for detecting antibodies to group-specific antigens of group A Streptococcus on the base of conjugated N-acetylglucosamine and its use in medical practice]. / Immunofermentnaia test-sistema dlia opredeleniia antitel k gruppospetsificheskomu antigenu streptokokka gruppy A na osnove kon'iugirovannogo N-atsetilgliukozamina i ee primenenie v meditsinskoi praktike.

Enzyme immunoassay kit has been created for detecting antibodies to group A Streptococcus, based on N-acetylglucosamine. N-acetylglucosamine was selected as the group-specific determinant due to the structure of group A Streptococcus polysaccharide, in which this monosaccharide residue is lateral to the main polysaccharide chain and hence more available for antibodies. Water-soluble polyacrylamide is the carrier in this kit, for this carrier is stable and not liable to nonspecific reaction with proteins. In addition, the synthesis of polyacrylamide conjugates ensures reproducible results. Use of this kit permits the identification of group A streptococcal etiology of the disease and thus carry out appropriate therapy; moreover, it helps predict the outcome of an acute streptococcal infection and detect the poststreptococcal complications in the early period of the disease.

[Reactivation of UV inactivated Escherichia coli cell extracts of propionic acid bacteria: fractionation of the extract]. / Reaktivatsiia inaktivirovannykh ul'trafioletovym svetom Escherichia coli kletochnym ékstraktami propionovo-kislykh bakterii fraktsionirovenie ékstrakta.

Cell free extract from Propionibacterium shermanii VKM-101 partially reactivates Escherichia coli AB 1157 irradiated by UV light. Fractionation of extract followed by the estimation of protective effect of fractions showed that this effect is linked to two fractions of soluble proteins. The fraction of cell walls, ribosomes and nucleic acids were poorly effective. Two active protein fractions (I-20-40% (NH4)SO4 and II-60-80% (NH4)2SO4) were separated by HPLC chromatography into 7 and 8 subfractions respectively. The activity was localised in subfraction N4 (fraction I) and N5.6 (fraction II).