The Effect of Drugs with α-Glutamyl-Tryptophan for Cytokine Secretion and Level of Surface Molecule ICAM-1 In Vitro.

The study of the molecular mechanisms underlying the action of immunomodulatory drugs is important for substantiating their therapeutic effect. In the present work, spontaneous and TNFα-induced secretion of IL-1α and IL-8 pro-inflammatory cytokines, as well as the level of the ICAM-1 adhesion molecule in EA.hy 926 endothelial cell culture and peripheral blood mononuclear cells of healthy donors, is studied using an in vitro model of inflammation in the presence of α-glutamyl-tryptophan (α-Glu-Trp) and Cytovir-3. The aim was to evaluate cellular mechanisms mediating the immunomodulatory effect of α-Glu-Trp and Cytovir-3 drugs. It was shown that α-Glu-Trp reduced TNFα-induced IL-1α production and increased TNFα-stimulated level of the ICAM-1 surface molecule of endothelial cells. At the same time, the drug reduced secretion of the IL-8 cytokine induced by TNFα and increased the spontaneous level of ICAM-1 in mononuclear cells. Cytovir-3 had an activating effect on EA.hy 926 endothelial cells and human peripheral blood mononuclear leukocytes. In its presence, there was an increase in the spontaneous secretion of IL-8 by endothelial and mononuclear cells. In addition, Cytovir-3 increased the level of TNFα-induced ICAM-1 on endothelial cells and increased the spontaneous level of this surface molecule on mononuclear cells. Suppression of stimulated production of pro-inflammatory cytokines under the action of α-Glu-Trp both separately and as a part of Cytovir-3 may determine its anti-inflammatory properties. However, an increased level of the surface ICAM-1 molecule indicates mechanisms that enhance the functional activity of these cells, which is equally important for the implementation of an effective immune response to infection and repair of damaged tissues during inflammatory response.

[Possibilities of therapeutic correction of ENT pathology associated with COVID-19 in children on an outpatient basis]. / Vozmozhnosti terapevticheskoi korrektsii patologii nosoglotki, assotsiirovannoi s COVID-19, u detei v ambulatornykh usloviyakh.

OBJECTIVE: To evaluate the therapeutic and preventive efficacy of the drug with antiviral and immunotropic activity Cytovir-3 in children with COVID-19 on an outpatient basis. MATERIAL AND METHODS: A retrospective analysis the treatment of 52 pediatric patients aged 1 to 17 years with a confirmed new coronavirus infection SARS-CoV-2 with the drug Cytovir-3 was carried out. 28 people, contacts in the family, received the drug for prophylactic purposes. Clinical observation of patients was carried out with an assessment of the severity and duration of fever, the anosmia, catarrhal symptoms in the nasopharynx and analysis indicator of saturation. In the control group, there were 27 patients of the same age who received the medicine Umifenovir and 25 contact family members who did not receive the medicine for prophylactic purposes. RESULTS: The use of Cytovir-3 in the COVID-19 treatment in children led to a decrease in intoxication symptoms 3.2-3.4 days after taking the medicine, a significant reduction of anosmia period recovery time, and elimination of the pathogen according to PCR analysis. The patients receiving the drug did not have ENT- complications and did not require hospitalization. Prophylactic administration of the drug in contact family members statistically significantly reduced the likelihood of developing the disease 3.6 times. The clinical efficacy and feasibility of using Cytovir-3 in the treatment and prevention of new coronavirus infection in patients of different ages has been shown.

Comparative efficiency of pathogen treatment of acute respiratory viral infections.

The article presents the results of clinical studies on the comparative effectiveness of different forms of the drug Cytovir-3 (syrup and powder for solution for oral administration) and Immunal l in the treatment of acute respiratory viral infections in children. It was found in a comparative randomized parallel-group study of 90 children aged two through six years that the drug Cytovir-3 (syrup and powder) became active faster than the comparison drug Immunal, providing normalization of body temperature, reduction of some manifestations of the general intoxication and respiratory syndrome, as well as elevated levels of serum immunoglobulin A. All drugs in the study had an equally normalizing effect on the content of peripheral blood leukocytes and erythrocyte sedimentation rates. The compared products were characterized by good tolerability, lack of side effects and high preventive efficacy against respiratory disease complications. Cytovir-3 drugs (syrup and powder for oral solution) and Immunal had similar ratios of clinical and laboratory safety, efficacy and tolerability. Both products can be used for the treatment of respiratory diseases in children aged two through six years.

[Clinical and laboratory presentation of the influenza A (H1N1pdm 2009) in children and adults during the period of 2009-2013 in St. Petersburg].

Comparative analysis of the clinical laboratory data from 419 children and 468 adults hospitalized during the pandemic of A (H1N1pdm 2009) and pre- and post-pandemic periods (2010-2013) showed that the clinical presentation of the pandemic influenza in patients of all ages is generally typical for influenza, and its character is determined by the degree of involvement of lungs in the process. Besides, the incidence of pneumonia in adults is statistically significantly higher than in children. During all compared periods hyperthermia (≥ 39 degrees C), hemorrhagic and dyspeptic syndrome were observed. Some differences in the main clinical manifestations of pneumonia in recovered patients and patients who died of the severe pandemic influenza were observed. The regularities of the cytokine reactions depending on the intensity of intoxication and occurrence of complications were determined in patients of all ages. Medical efficacy of inclusion of antiviral chemotherapeutic agents into complex influenza treatment was proved.

[The application of synthetic peptides to characterize the site-directed antiviral humoral immune response in patients with respiratory syncytial viral infection].

The article deals with the study of characteristics of epitope-specific humoral immune response to respiratory syncytial viral infection depending on nature of disease and patients' age. The couple serums from 226 children and adults with respiratory syncytial viral infection were analyzed. To detect in enzyme immunoassay the epitope-specific IgG the synthetic peptides were applied imitating the structure of functionally depended epitopes of F-protein of respiratory syncytial virus with amino acid sequences 221-232 (F = SP12), 479-491 (F-SP13) and G-protein with amino acid sequences 152-164 (G-H13), 184-198 (G-T15). The respiratory syncytial viral infection neutralizing antibodies were detected using the microneutralization reaction. The rate of seroconversions of epitope-specific IgG consisted 21-25% in children 3-18 years old under primary respiratory syncytial viral infection and increased up to 42-50% in children 3-18 years old and adults under recurrent episodes of diseases. In these groups, the seroconversions of respiratory syncytial virus neutralizing antibodies were observed in 42%, 65% and 58% of cases correspondingly. Independently of age of patients with diagnosed respiratory syncytial viral infection, the absence of conversions of neutralizing antibodies was statistically significant associated with the absence of response from epitope-specific IgG. The presence among B-cell epitopes of immune dominance of surface glycoproteins of respiratory syncytial virus in patients with recurrent (but not primary) respiratory syncytial viral infection is detected The hierarchy of epitope-specific immune response in case of complicated course of disease (response activity to epitopes: SP12 = G-T15 > G-H13) differed from the case of uncomplicated course of disease.

Interferon status in children during acute respiratory infections. Therapy with interferon.

We studied interferon status in children during acute respiratory infections and found that it depends on etiology, course of the disease, and individual features of the organism. The efficiency of IFN inductor anaferon (pediatric formulation) and the possibility of its application in the therapy of children with acute respiratory infections were demonstrated.

Acute viral infections with combined involvement of the respiratory and gastrointestinal tracts in children. Therapy with interferon.

We evaluated the percent of acute respiratory viral infections with gastrointestinal syndrome in the structure of morbidity in babies aging 6 months and elder. Therapeutic efficiency and safety of anaferon (pediatric formuation) as a component of complex therapy of acute respiratory viral infections with involvement of the gastrointestinal tract were proven; more rapid disappearance of all symptoms and improvement of the immune status parameters were demonstrated.