Polyoxidonium Research Articles

Neutrophil extracellular traps as an important part of the pathogenesis of chronic rhinosinusitis without polyps

Background. Chronic sinusitis occurs in the Russian Federation in 16.4±10.89% of the population and has a great impact on the quality of life of patients. The inflammatory process underlying this pathology is often resistant to conservative treatment and causes surgical intervention. The study of the role of neutrophil extracellular traps as an important part of the immune response, as well as the capabilities of drugs capable of influencing the processes of netosis, is an important and relevant area of modern research. Aim. Studying the role of NETs in the pathogenesis of CRS without polyps, assessing the effect of azoximer bromide on the metabolism of NETs in patients with CRS. Materials and methods. The study included 82 patients diagnosed with chronic rhinosinusitis (average age 37±12 years), and 40 healthy volunteers (average age 34±10 years). Patients with CRS were treated with surgery and a course of azoximer bromide, the severity of the disease did not differ in patients. Nasal secretions and venous blood were analyzed in all study participants with the determination of surrogate markers of neutrophil extracellular traps – myeloperoxidase complexes with DNA and the detection of double-stranded DNA (Quant Pico Green dsDNA kit). In patients who received azoximer bromide, the material was taken twice – before the start of treatment and 10 days after the course of treatment. Results. In patients with CRS, the amount of NETs in nasal secretions and venous blood is higher compared to the control group (p0.05). The use of azoximer bromide in CRS outside of exacerbation reduces the activity of NETosis processes with intranasal use of the drug not only in the area of inflammation (reduction of NET in nasal secretions); p0.05, but also at the general level (decrease NETs in venous blood); p0.05. Conclusion. An increase in the amount of NETs in nasal flushes and venous blood in patients with CRS without exacerbation compared with the control group may indicate a likely pathological role of NETosis processes, and an increase in the amount of NETs in the blood of patients with CRS without exacerbation compared with the control group indicates the systemic effect of a local inflammatory process in the mucous membrane of the nasal cavity and paranasal sinuses.

Effect of drugs of various groups on the pharmacokinetics of cefotaxime in comparison with their effect on lymphatic tissue drainage

Introduction. The lymphatic system plays a key role in spreading pathogens, including those causing intraabdominal infections. An urgent task of pharmacology is to create methods for the targeted delivery of antibiotics to lymphatic vessels and intestinal tissues. One approach is to use agents acting as endolymphatic conductors to achieve a high drug concentration in the lymphatic system. Aim. To evaluate the effect of various drugs on the concentration of cefotaxime, a third-generation antibiotic, in blood and intestinal tissues, as well as on lymphatic drainage in experiments on mice. Materials and methods. We investigated the effect of hyaluronidase (HLRD), bovgialuronidase azoximer (BovGLRD+Az), terrilitin (TRL), papaya milky juice (PMJ ), sodium heparin (HepS ), aprotinin (APRT), azoximer bromide (AzBrom), furosemide (FRSD) and sodium deoxyribonucleate (DRN) on the removal time of lymphotropic dye from mouse mesentery and the cefotaxime concentration in blood plasma and intestinal tissues by high-performance liquid chromatography. Results. HLRD reduced the time of dye removal from the mesentery by 26.2%, BovGLRD+Az – by 33.5%, TRL – by 36%, PMS – by 23.1%, HepS – by 30.1%, APRT – by 34.6%. The differences in lymphostimulating activity between these drugs were not statistically significant. AzBrom and FRSD increased the dye removal time by 8.3% and 6%, respectively; the DRN had no effect. HLRD, BovGLRD, TRL, PMJ, HepS and APRT increased the CF concentration in blood and intestinal tissues 1.5 and 24 hours after injection, in contrast to the single injection of antibiotic. AzBrom increased the CF concentration only after 1.5 hours. FRSD increased the antibiotic concentration in intestinal tissues but not in blood plasma. The DRN did not affect the studied indicators. Conclusion. Lymphostimulating drugs HLRD, BovGLRD, TRL, PMJ, HepS and APRT effectively direct the antibiotic to the lymphatic system and can be used for lymphotropic therapy.

Effect of Azoximer Bromide on Individual Genomic and Proteomic Characteristics of the Strain during Cultivation of Yersinia pestis EV NIIEG

Effect of Azoximer Bromide on Individual Genomic and Proteomic Characteristics of the Strain during Cultivation of Yersinia pestis EV NIIEG

Assessment of the effect of using immunomodulatory drugs for emergency prevention of experimental plague caused by a virulent strain of the main subspecies Yersinia pestis

Introduction. Immunomodulatory drugs (IMD) have great potential to increase the nonspecific reactivity of the organism in a set of measures for emergency prevention of plague. The purpose of the work is to evaluate the protective effectiveness of the use of IMD of different groups in experiments on modeling infection with a highly virulent strain of the plague microbe. Materials and methods. IMD (rIFN-γ — recombinant interferon-gamma, PO — azoximer bromide, synthetic immunomodulatory oligopeptides O1, O2, O3) was administered to white mice and guinea pigs subcutaneously thrice by the schedule 3 days, 1 day, and 1 hour prior the infection with a virulent test strain of plague Yersinia pestis 231 (708) at dose from 1 to 625 CFU. In addition, the effect of IMD on the production of IFN-γ and interleukin-10 was investigated in white mice before infection. Results. The study of the effect of IMD on the survival of unvaccinated biomodels made it possible to establish that only rIFN-γ and PO increase the survival of two types of laboratory animals by 20–50% and significantly increase the LD50. All tested IMD contribute to an increase in the average life expectancy of biomodels by at least one day. An increase in spontaneous and mitogen-induced cytokine production was found only in white mice receiving rIFN-γ and PO, which correlates with animal survival rates. Conclusion. The obtained data indicate the effectiveness of the use of IMD, especially rIFN-γ and PO in protecting the macroorganisms from infection with Y. pestis, which determines the prospects for research on the further improvement of emergency prevention of plague.

MORPHOFUNCTIONAL CHANGES IN LYMPH NODES DURING INTRALYMPHATIC IMMUNOSTIMULATION WITH VARIOUS DRUGS IN A RAT MODEL

Using an experimental rat model, we analyzed the morphofunctional state of mesenteric lymph nodes after intralymphatic administration of various immunostimulants. Material and Methods: The effect of four drugs was studied on 100 male rats: acid peptidoglycan, azoximer bromide, hexapeptide (arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine) and aminodihydrophthalazinedione sodium. We studied morphometrically the average size of lymph nodes, the size of germinal centers, the density of lymph nodes, and calculated the mitotic activity index and migratory activity index. Results: All experimental groups showed changes characterized by morphological restructuring of the lymph nodes, which was accompanied by an increase in their reactivity and provided an immunostimulating effect. In a dynamic study of the condition of the lymph nodes during the intralymphatic administration of various immunomodulators, it turned out that changes occur at different times. With the introduction of APG, the greatest structural changes occurred on the day 3 of the experiment. In the case of intralymphatic administration of AB, peak changes occurred on days 7-14 from the start of administration. In the third and fourth groups, using HP and ADPS, structural restructuring of the lymph nodes occurred on days 14-30. Conclusion: When extrapolating the data obtained to the clinical plane, we can conclude that intralymphatic administration of APG can be recommended in the acute period of the disease, intralymphatic administration of AB - in the case of subacute course of the disease, whereas the use of HP and ADPS will be effective during the period of convalescence.

MORPHOFUNCTIONAL CHANGES IN LYMPH NODES DURING INTRALYMPHATIC IMMUNOSTIMULATION WITH VARIOUS DRUGS IN A RAT MODEL

Using an experimental rat model, we analyzed the morphofunctional state of mesenteric lymph nodes after intralymphatic administration of various immunostimulants. Material and Methods: The effect of four drugs was studied on 100 male rats: acid peptidoglycan, azoximer bromide, hexapeptide (arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine) and aminodihydrophthalazinedione sodium. We studied morphometrically the average size of lymph nodes, the size of germinal centers, the density of lymph nodes, and calculated the mitotic activity index and migratory activity index. Results: All experimental groups showed changes characterized by morphological restructuring of the lymph nodes, which was accompanied by an increase in their reactivity and provided an immunostimulating effect. In a dynamic study of the condition of the lymph nodes during the intralymphatic administration of various immunomodulators, it turned out that changes occur at different times. With the introduction of APG, the greatest structural changes occurred on the day 3 of the experiment. In the case of intralymphatic administration of AB, peak changes occurred on days 7-14 from the start of administration. In the third and fourth groups, using HP and ADPS, structural restructuring of the lymph nodes occurred on days 14-30. Conclusion: When extrapolating the data obtained to the clinical plane, we can conclude that intralymphatic administration of APG can be recommended in the acute period of the disease, intralymphatic administration of AB - in the case of subacute course of the disease, whereas the use of HP and ADPS will be effective during the period of convalescence.

Experience of using immunomodulatory therapy in the complex treatment of mild community-acquired pneumonia and its long-term results

A decrease of nonspecific body resistance, an imbalance of local and systemic immunity and a free-radical oxidation abnormality substantially contribute to the pathogenesis of community-acquired pneumonia (CAP).Purpose: To study the efficiency of including immunomodulators into the comprehensive treatment of nonsevere community-acquired pneumonia and assess the long-term effects of the treatment conducted.Patients (n = 55) with non-severe CAP (41 (31-48) years old, with CRB-65 score of 0.15 (0-1)) are included in the study. Group 1 (control) received only standard CAP therapy; the other two groups received immunomodulators concurrently with the standard therapy: bacterial lysate (BL) for group 2 and azoximer bromide (AzB) for group 3. TNFα and IL-6 concentration was determined on the day of visit, on day 13 and day 60 of follow-up. During 2 years, the incidence of low respiratory tract infections (LRTI) was studied in the same patients with CAP in past (n = 55). All patients (n = 55) had clinical signs of non-severe community-acquired pneumonia. The overall duration of all symptoms was lower in immunomodulators groups as compared to the control group: 12 (11-13) days in BL group (p < 0.001) and 12 (11-12) days in AzB group (p < 0.001) with no statistically significant difference between intervention groups (p = 0.36). During treatment, TNFα and IL-6 concentration decreased on day 13 and day 60 in all patients; in patients who received immunomodulators, TNFα and IL-6 were reliably lower as compared to the control. Changes of TNFα and IL-6 concentration in the groups on day 60 of the study as compared to the baseline showed a decrease in BL group by 85 (-89 – -82) % and 86 (-90 – -85) % (p < 0.001; p = 0.001 and control); in AzB group by 82 (-86 – -80) % and 86 (-88 – -84) % (p = 0.002; p = 0.007 and control). Intensity of IL-6 concentration decrease on day 60 in BL and AzB groups did not differ (p = 0.72). Gender- and age-adjusted odds ratio for the development of low respiratory tract diseases (during 2 years after CAP) in AzB group was 0.15 (0.02-0.93) (p = 0.04) suggesting its protective effect. Inclusion of immunomodulators in basic treatment of non-severe community-acquired pneumonia reduces duration of symptoms and is associated with improvement of the proinflammatory cytokine profile. In 2 years of follow-up, long-term effects of the immunomodulatory therapy showed statistically significant lower incidence of low respiratory tract infections in AzB group only.

Azoximer bromide and hydroxyapatite: promising immune adjuvants in cancer.

Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations. There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers. Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response, followed by the adaptive immune response. The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells. Most immune adjuvants are associated with a vaccine or incorporated into the new generation of mRNA vaccines. Few immune adjuvants are used as drugs. Hydroxyapatite (HA) ceramics and azoximer bromide (AZB) are overlooked molecules that were used in early clinical trials, which demonstrated clinical efficacy and excellent tolerance profiles. HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas. AZB, an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia, the Commonwealth of Independent States, and Slovakia for infectious and inflammatory diseases, is and now being developed for use in cancer with promising results. These two immune adjuvants can be combined in various immunotherapy strategies.

A comparative study of the effectiveness of azoximer bromide and surgery on the quality of the life of patients with chronic rhinosinusitis without nasal polyps

The aim of this study was to compare the effects of azoximer bromide and surgery on the quality of life of patients with chronic rhinosinusitis (CRS) without polyps. We also wanted to examine changes in the patient's emotional state and the nature of their complaints. The results of using the Visual Analogue Scale (VAS) and the Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire in patients with CRS without severe or moderate-severe polyps, before treatment and 3 months after treatment, are presented. Patients, depending on their choice, were treated with functional endoscopic intervention or a course of 6 mg/ml azoximer bromide (1 ml per day, a course of at least 10 days). The median [interquartile range] score for VAS in patients before azoximer bromide treatment was 6.7 [6.3; 7.05] points, after treatment 4.2 [3.50; 4.70] points. The median [interquartile range] of VAS scores in patients before surgical treatment was 6.4 [6.1; 6.9] points, and after 4.8 [4.50; 5.30] points. The median [interquartile range] of the SNOT-22 score before azoximer bromide treatment was 33 [32; 36] points, after treatment - 24 [22; 25] points. The median [interquartile range] of the SNOT-22 score before surgery was 34 [32; 36] points, after treatment - 19 [18; 21.25] points. Azoximer bromide treatment and surgery improve the quality of life of patients with CRS (according to the visual analog scale and all SNOT-22 domains) during a control survey after 3 months (p<0.001). Surgical treatment has a stronger impact on the quality of life, which is more noticeable in the influence on the domains "Rhinological symptoms", "Extranasal symptoms", "Ear/facial symptoms" (p<0.05). According to the domains "Psychological dysfunction", "Sleep dysfunction", surgical intervention had no advantages in affecting the quality of life, compared with taking azoximer bromide (p<0.05).

Эффективность применения препарата азоксимера бромид в профилактике, лечении и иммунореабилитации COVID-19

The review presents the features of immunopathogenesis in a new coronavirus infection (COVID-19) and the possibility of correcting the state of the immune system of the patients with the help of a modern domestic synthetic immunomodulator azoximer bromide (Polyoxidonium®). The results of large-scale studies with the inclusion of the drug in the schemes of complex pathogenetic treatment of COVID-19 and immunorehabilitation in post-COVID-19 syndrome (PCS), as well as the possibility of its use for the prevention of acute respiratory infections and COVID-19 in persons with a high risk of infection are considered. High efficacy and safety of azoximer bromide in normalization of the condition in patients, even with severe complicated forms requiring hospitalization in intensive care units (ICU), in reducing the incidence of complications, acute symptoms in post-COVID-19 syndrome, as well as preventing the spread of SARS-CoV-2 virus in the population and the development of symptoms of a new coronavirus infection during prophylactic administration of the drug have been shown. Key words: COVID-19 immunopathogenesis, COVID-19 immunocorrection, azoximer bromide (Polyoxidonium®)

Evaluation of the effectiveness of the proposed therapy on energy metabolism parameters in patients with chronic liver lesions on the background of secondary immunodeficiency state

Objective: to study the effect of a combination of azoximer bromide (AB) and human placenta hydrolysate (HPН) on metabolic processes in patients with chronic liver lesions on the background of secondary immunodeficiency. Materials and methods: 95 patients with chronic liver pathology on the background of secondary immunodeficiency (VIDS) aged 35 to 56 years were examined. The main group is 45 people, and the comparison group is 50 people. After a general clinical and bacteriological examination, all patients were subjected to the study of metabоlic processes. The assessment of metabolic disorders was carried out by the level of macroergic compounds in the hemolysate of the washed suspension of erythrocytes of patients by thin-layer chromatography. In addition to treatment with conventional methods, patients who were under observation were additionally prescribed a combination of drugs — bromine azoximer and human placenta hydrolysate. Patients of the comparison group received milk thistle preparations as a hepatoprotector and did not use any immunoactive drugs. Results: when studying the state of indicators of metabolic disorders after the completion of treatment, it was found that patients in the main group who received AB and HPН had almost complete normalization on the part of the studied indicators, which cannot be said about patients from the comparison group who received only conventional drugs in average therapeutic doses in the treatment complex. Conclusions: from the data obtained, it is possible to judge the positive effect of AB and HPН on the indicators of the state of energy homeostasis and consider it pathogenetically justified and clinically promising to include their combination in the complex of treatment of patients with CLP against the background of VIDS.

Use of immunomodulatory therapy as part of comprehensive treatment of non-severe community-acquired pneumonia and its long-term results.

This study investigates the efficiency of two different types of immunomodulators for the treatment of non-severe community-acquired pneumonia (CAP) and assesses their long-term effects. The study included 55 patients with non-severe CAP. Group 1 (control) received only standard CAP therapy; the other two groups received immunomodulators simultaneously with the standard therapy: bacterial lysate for group 2 and azoximer bromide (AzB) for group 3. TNF and IL-6 concentrations were determined on the day of hospitalization as well as on days 13 and 60 of follow-up. For 2 years, we monitored the incidence of low respiratory tract infections (LRTIs) in the same patients with CAP (n=55). The overall duration of all symptoms was lower in the immunomodulator groups compared with the control group. During treatment, TNF and IL-6 concentrations decreased on days 13 and 60 in all patients; in patients who received immunomodulators, TNF and IL-6 were reliably lower than in control patients. IL-6 concentration decreased on day 60 in the bacterial lysate and AzB treatment groups and did not differ (p=0.72). The odds ratio for the development of LRTIs in the AzB group was 0.15 (0.02-0.93) (p=0.04), suggesting its protective effect. Inclusion of immunomodulators in the basic treatment of non-severe CAP reduces the duration of symptoms and is associated with improvement of the pro-inflammatory cytokine profile. In 2 years of follow-up, the long-term effects of the immunomodulatory therapy showed a statistically significant lower incidence of LRTIs in the AzB group only. However, given the small sample size of this study, further clinical studies are needed.

Intrauterine adhesions: from pathogenesis to effective coping technologies

Intrauterine adhesions (IUDs) are one of the unresolved and unsolved problems of modern reproductive medicine worldwide. Adhesive lesions lead to partial or complete obliteration of the uterine cavity and/or cervical canal. The main clinical manifestations of IUDs are menstrual irregularities, cyclical pain, infertility and other various reproductive disorders. Reproductive outcomes in women with IUDs remain poorly understood and difficult to verify. At the same time, there is currently no understanding of the basic mechanisms of IUD development, including the processes explaining the failures of the above complications. The problem of overcoming IUD recurrences after adhesiolysis remains far from being finally resolved. The gold-standard treatment for IUD is hysteroscopic adhesiolysis, which, however, is associated with a high frequency of complications and relapses, highlighting the need for preventive approaches to the management of IUD. The drugs with enzymatic activity inhibiting abnormal connective tissue include bovhyaluronidase azoximer created by the Russian developers back in 2005. The drug consists of two components – hyaluronidase and azoximer bromide. The former is an enzyme, and the latter is a stabilizer that prolongs the action of hyaluronidase. Several studies have shown that bovhyaluronidase azoximer causes the destruction of intrauterine adhesions and restores the endometrium status in inflammatory pelvic diseases. Due to prolonged antifibrotic effect of bovhyaluronidase, azoximer can be used to treat women with IUDs to reduce the risk of the subsequent development of adhesive process in the uterine cavity.

Analysis of pathogenetic manifestation of decompensated intestinal dysbacteriosis in cats

Despite the creation of more and more new generations of antibacterial agents, the correction of intestinal dysbiosis in animals currently remains one of the most complex and urgent problems in clinical veterinary medicine. The article presents an analysis of the pathogenetic manifestation (microbial background, hematological analytes) in decompensated intestinal dysbacteriosis in domestic cats in the dynamics of its correction. The aim of the study was to study the comparative effectiveness of various pharmacotherapy regimens for decompensated intestinal dysbacteriosis in cats. The data shows that when correcting decompensated intestinal dysbacteriosis in domestic cats, the most rational treatment regimen is the complex use of Lactobifadol probiotic (contains at least 1.0 106 CFU/g of lactic acid bacteria Lactobacillus acidophilus LG1-DEP-VGIKI and 8.0 107 CFU/g of bifidobacteria Bifidobacterium adolescentis B-1-DEP-VGNKI), Vetelact prebiotic (contains lactulose - not less than 50 %), Azoksivet immunomodulator (contains 1.5 mg of azoximer bromide in 1 ml), as well as infusion therapy (intravenous drip injection of 10 ml/kg of 0.9 % sodium chloride solution; 10 ml/kg of 5 % glucose solution; 5 ml/kg of rheosorbelact and 2.5 ml/kg of refortan). This was confirmed by the results of pathogenetic picture (analysis of the microbial background and individual hematological analytes), in the dynamics of pharmacotherapy, namely before the start of correction, as well as on days 7 and 14. The improvement of diagnostic approaches and methods for correcting the most severe degree of intestinal dysbacteriosis (the stage of decompensation) creates prerequisites for the future study of dysbiotic disorders of the intestinal tract in other animal species, considering the severity of its manifestation.

Эпидемиологическая и клиническая эффективность приема азоксимера бромида для профилактики острой респираторной инфекции и COVID-19 среди медицинских работников

Background. Acute respiratory infections (ARIs) account for over 90% of all infectious diseases in the Russian Federation. During the COVID-19 pandemic, with no causal therapy developed so far, it is important to pay attention to preventive drugs. Objective. To assess the epidemiological and clinical efficacy of azoximer bromide (Polyoxidonium®) for the prevention of ARIs and COVID-19 in the vulnerable groups (healthcare professionals). Patients and methods. We performed an observational, prospective, selective study to assess the impact of azoximer bromide (AzB) on the incidence and tolerability of ARIs and SARS-CoV-2 infection among healthcare professionals in the Russian Federation. This study was conducted between April and August 2020 and included 476 participants. Of them, 311 individuals were in the experimental group (AzB+), whereas 165 individuals served as controls (AzB-). Patients in the experimental group received 1 tablet of azoximer bromide twice a day for 10 days. We evaluated the incidence of ARIs and COVID-19 (epidemiological efficacy) and disease severity (clinical efficacy). We surveyed the participants using a special questionnaire 3 months following treatment initiation or inclusion in the control group. Statistical analysis was performed using the R v. 3.6.3 software. Differences were considered significant at p &lt; 0.05. Continuous variables were described by the number of observations (n), means, 95% confidence intervals (CIs) for means, medians (Me), and interquartile ranges (IQR). Categorical variables were presented as the absolute number of observations, percentages, and two-sided CIs. Results. We found that participants in the AzB+ group demonstrated a 43.3% lower ARI risk than controls (p &lt; 0.001). The risk of COVID-19 was decreased by 71.4% (p &lt; 0.001). We also demonstrated that AzB was effective in reducing ARI severity. Participant from the AzB+ group who developed some respiratory infections presented with a milder disease and 33.2% less common lower respiratory tract symptoms (such as cough, shortness of breath, and chest pain) (p &lt; 0.001). The incidence of pneumonia in the experimental group was 14.1% lower than that in the control group (5.3%–22.9%) (p = 0.029). Conclusion. Thus, azoximer bromide used as a preventive measure or as a part of comprehensive therapy decreased the incidence of ARIs and COVID-19 among healthcare professionals and alleviated the disease, which suggests its high epidemiological and clinical efficacy. Key words: acute respiratory infections, COVID-19, Azoximer bromide, prevention, comprehensive therapy, healthcare professionals

Иммунокоррекция в терапии COVID-19 у амбулаторных пациентов

Objective. To evaluate the clinical efficacy of including Azoximer bromide in the complex outpatient treatment for individuals with a confirmed diagnosis of COVID-19 with moderate to severe symptoms. Patients and methods. This study included 40 patients who were treated for a novel coronavirus infection (COVID-19) in outpatient settings in Ufa in September to November 2021. Patients were divided into two groups: the study group (n = 20), where Azoximer bromide was included in the complex treatment, and the comparison group (n = 20), which received only standard therapy. The dynamics of clinical presentation and laboratory parameters characterizing inflammation served as a criterion for assessing the effectiveness of treatment. Results. The results of the study showed that patients receiving Azoximer bromide had relief of respiratory syndrome 3 days earlier than in the comparison group. This included disappearance of such symptoms as cough, sputum separation, and normalization of respiratory rate. The objective criterion to assess the efficacy of Azoximer bromide therapy were the findings of multi-slice computed tomography (MSCT) against the background of complex treatment with inclusion of Polyoxidonium – the percentage of lung parenchymal lesions did not exceed 8% on day 17 of treatment; in the comparison group, 6 patients had the percentage of lung parenchymal lesions up to 12% on day 17 of treatment according to MSCT. In the remaining patients in the comparison group, the percentage of lung lesions was comparable to the results in the study group. Analysis of the manifestations of multisystem inflammatory syndrome revealed that the period of normalization of body temperature (&lt;37°C) in patients receiving immunomodulatory therapy was 13.20 ± 2.45 days versus 17.70 ± 2.53 days in the comparison group (p = 0.0001). A white blood cell (WBC) count and erythrocyte sedimentation rate (ESR) against the background of treatment in the study group normalized on average 2 days faster, although there were no significant differences between the groups. In the study group, WBC count and ESR on admission were 3.9 × 109/L and 40 mm/h, respectively, after treatment – 6.3 × 109/L and 18.6 mm/h, respectively. In the comparison group, these indices were 3.8 × 109/L and 39 mm/h on admission and 6.2 × 109/L and 20.6 mm/h after treatment, respectively. The level of C-reactive protein also decreased in both groups, amounting to 7.18 ± 3.06 mg/L and 3.744 ± 1.73 mg/L on day 17 of treatment in the study group and comparison group, respectively, which was more than 2 times lower than baseline levels in both groups. Conclusion. Inclusion of Azoximer bromide in the complex treatment of patients with a novel coronavirus infection allows to achieve faster normalization of patients’ condition, which is accompanied by positive clinical dynamics manifested in faster relief of multisystem inflammatory syndrome and lung parenchymal lesions compared to patients who were only on standard therapy. No adverse events were observed during medication administration. Key words: coronavirus infection, SARS-CoV-2, COVID-19, pneumonia, immune correction, Azoximer bromide

Polymeric Approach to Adjuvant System in Antibody Production against Leishmaniasis Based on Hybridoma Technology.

Leishmaniasis is a zoonotic disease, which is one of the serious public health problems in the world. Nowadays, antibody production using hybridoma technology may be a correct approach in terms of sensitivity in the diagnosis of diseases such as leishmaniasis. The aim of this study was investigation of the effectiveness of different adjuvants on polyclonal antibody production against L. tropica based on hybridoma technique. Accordingly, Freund's adjuvant (1956, M. tuberculosis), as a classic adjuvant in studies, was used comparatively with the non-toxic polymeric based Polyoxidonium adjuvant. All animal immunization procedures were conducted at Bezm-i Alem University Experimental Animal Research Center. The adjuvant response was tested both in the serum sample and in the antibodies produced by the hybridomas. The antibody titers were determined with ELISA. Freund's and Polyoxidonium (PO) group blood titer's increased approximately 5.5 fold compared to control after the 6th and 8th immunization. Hybridomas produced from mice immunized with PO adjuvant induced only antigen-specific antibody response and did not develop an immune response against the adjuvant. Adjuvant selection is very important in terms of the specificity of antibody responses of cells produced in hybridoma technology. Therefore, PO is recommended as a new adjuvant system in this study.

Клиническая оценка комплексного лечении больных с герпетическим кератитом при применении азоксимер бромида

A significant place among the causes of blindness and low vision among the adult population is occupied by keratitis and keratouveitis. Most often, this disease of the cornea is caused by the herpes simplex virus (in 20–57 % of cases among the adult population and in 70–80 % of cases among children). The results of the treatment in the main group of patients with GC were considered satisfactory in 6 patients (6 eyes), in 10 patients (10 eyes) with keratitis, good treatment results were achieved. In comparison with the control group, the use of Polyoxidonium in complex treatment made it possible to improve the results of treatment by 14.3 % (p &gt; 0.05). Keywords: herpetic keratitis, keratouveitis, azoximer bromide, Polyoxidonium, herpes simplex virus, antiviral therapy, blindness, low vision

The feasibility of immunocorrective therapy in the treatment of children with new tuberculosis cases

Aim. To substantiate the expediency of the immunocorrective therapy use in combined treatment by studying the effectiveness of the immunomodulator azoximer bromide aimed at correcting the immunological changes in children with new tuberculosis (TB) cases. Materials and methods. The study on the effectiveness of immunocorrective therapy in the complex treatment of children with new TB cases was conducted at the beginning of antimycobacterial therapy (AMBT) and at the end of the maintenance phase (MF) of AMBT. For this purpose, 51 children with new TB cases and immunologic changes were included in the study and divided into 2 groups: 26 children received immunomodulator azoximer bromide in the combined therapy on the background of AMBT (main group) and 25 children were assigned to receive only AMBT (control group). The groups were identical in age, sex, prescribed AMBT regimens, and severity of the specific process. The children from the main group along with the standard AMBT additionally used azoximer bromide (immunomodulator) to correct immunological changes: for children under 10 years of age – 6 mg twice a day, for children over 10 years – 12 mg twice a day; the treatment course – 14 days. The study results were processed on a personal computer using the statistical package of the licensed program Statistica, version 13 (Copyright 1984–2018 TIBCO Software Inc. All rights reserved, License No. JPZ804I382130ARCN10-J). Results. Given the results obtained, the use of immunomodulator azoximer bromide in the complex treatment for children with new TB cases, alongside normalization of all cytokine profile indicators and the balance in the regulatory system of pro- and anti-inflammatory cytokines, helped to achieve by the end of treatment: a shorter average time to culture conversion by 0.9 (1.5 (1.0; 2.0) months against 2.4 (2.0; 3.0) months; P &lt; 0.01), positive radiological dynamics of 77 % (χ2 = 5.79; P &lt; 0.01), reduced time of destruction healing by 2.1 (1.7 (1.0; 2.0) months against 3.8 (3.0; 4.0) months, P &lt; 0.02), shorter average time of the basic AMBT course by 1.5 (6.2 (5.6; 6.8) months against 7.7 (6.0; 9.3) months; P &lt; 0.01). Combined treatment tolerability was satisfactory in all 100 % of cases. Conclusions. Immunomodulator azoximer bromide as a part of the combined therapy for children with new TB cases can not only restore the body immune reactivity, but also reduce the specific process activity on the background of AMBT, shorten the average time to culture conversion by 0.9 months and destruction healing by 2.1 months, reduce the average duration of the main AMBT course by 1.5 months. In addition, this approach to therapy helps to conduct standard AMBT without changing the treatment regimen.

The effect of immunomodulator azoximer bromide on immunoglobulin levels in children with newly diagnosed tuberculosis

Aim. To analyze the effect of the immunomodulator azoximer bromide on serum immunoglobulins (IgE, A, M, G) in the complex treatment for children with newly diagnosed tuberculosis. Materials and methods. The study was included 51 with newly diagnosed tuberculosis children, which were divided into 2 groups: 26 children suffer from disease, who received immunomodulator azoximer bromide (main group) in combination treatment with antimycobacterial therapy (AMBT) and 25 children suffer from disease who received AMBT only (control group). The comparison group included 30 healthy children. The children from the main group on the background of standard AMBT additionally were used the azoximer bromide (immunomodulator) to correct immunological changes: in children under 10 years of age, 6 mg twice a day, in children over 10 years – 12 mg twice a day; course of treatment – 14 days. Research indicators such as IgE, A, M, G in serum were performed on the basis of the Immunological Department in the Training Medical and Laboratory center of ZSMU by solid-phase enzyme-linked immunosorbent assay (ELISA) using a device enzyme-linked immunosorbent reader Sirio S using reagent kits LTD RPL “Granum” (Kharkiv), units of measurement: IgE – IU/ml), IgA, M, G – g/l. The study was conducted at the beginning of intensive phase (IF) AMBT and at the end of the AMBT maintenance phase (MF). The study results were processed on a personal computer using the statistical package of the licensed program Statistica, version 13 (Copyright 1984–2018 TIBCO Software Inc. All rights reserved, License No. JPZ8041382130ARCN10-J). Results. Children with newly diagnosed tuberculosis, who received immunomodulator azoximer bromide in combination therapy, after the end of the AMBT MF was determined by the normalization of serum IgA levels (1.22 (0.75; 1.74) g/l against 1.70 (1.11; 2.01) g/l, P &lt; 0.02), which was 1.4 times lower than children who received only AMBT. The levels of IgE and M throughout the course of treatment were within the age norm with decreasing at the end of treatment, and the level of IgG throughout the course of treatment remained significantly higher than that of the healthy children group. Children with newly detected tuberculosis who received only AMBT, after the end of AMBT MF on the background of normal levels of IgE and M, the level of IgA remained significantly higher in 1.4 times, and the level of IgG tended to increase. Conclusions. Considering the obtained results, children with newly detected tuberculosis, who received of the immunomodulator azoximer bromide in complex treatment, helped to normalize of IgA level in serum, after completion of treatment. Therefore, the effect of the immunomodulator azoximer bromide in the complex therapy of children with newly detected tuberculosis on immunoglobulin indicators were significant, which would improve the effectiveness of antimycobacterial therapy in this contingent of patients in general.