Prospects for the use of bacterial lysates in the complex therapy of chronic adenoiditis

Introduction. Adenotomy is a common surgical procedure in childhood. In children with recurrent infections of the respiratory tract, hypertrophy of the pharyngeal tonsil, a sign of lymphoproliferative syndrome of a secondary immunodeficiency state, is characterized by reduced adaptive abilities of mucosal immunity with impaired biocenosis in chronic inflammation. Pharyngeal tonsil surgery is considered stressful in frequently ill children and therefore requires preoperative preparation. In this context, it is relevant to study the nature of changes in the factors of mucosal immunity in terms of cell destruction in the nasal secretion in the complex treatment of children with hypertrophy of the pharyngeal tonsil and chronic adenoiditis, as prevention of complications in the postoperative period of adenotomy.Aim. To increase the effectiveness of the treatment of chronic adenoiditis in children with recurrent infections of the respiratory tract using the combined effect of low-frequency ultrasonic cavitation with monochromatic unpolarized light and bacterial lysates.Materials and methods. In order to test the hypothesis about the possibility of canceling adenotomy in 77 children aged 3-6 years with hypertrophy of the pharyngeal tonsil, accompanied by chronic inflammation. The effectiveness of the complex treatment was assessed by the functional and metabolic status of nonspecific resistance factors in the nasal lavage.Results and discussion. The combined effect of low-frequency ultrasonic cavitation with photochromotherapy and bacterial lysates leads to the normalization of pathophysiological changes on the surface of the mucous membrane, leading to a balance of the qualitative and quantitative composition of the functional-metabolic status of NG, which makes it possible to postpone adenotomy. The best clinical result is observed when bacterial lysates are used in complex therapy in combination with physiotherapy in children with chronic adenoiditis and, to a certain extent, substantiate the advisability of a combined effect as a non-invasive and effective method.Conclusions. Topical bacteriolysate in a complex treatment regimen for children with recurrent infections of the respiratory tract against a background of chronic inflammation eliminates bacterial antigens and enhances the intrinsic defenses of the mucous membrane of the pharyngeal tonsil.

Immunoprophylaxis of influenza, acute and recurrent respiratory infections during the COVID-19 pandemic

The article notes features of the last epidemic season (2020-2021) in the form of extremely low activity of influenza viruses with SARS-CoV-2 remaining dominant in the etiological structure of acute respiratory viral infections. Presented own data indicating the heterogeneity of SARS-CoV-2 (Alpha, Delta, B.1.1.317, B.1.1.397, B.1.1.523) isolated from hospitalized patients was noted. An increase in the etiological role of bocavirus, alpha-coronavirus and metapneumovirus with a decrease in the frequency of parainfluenza viruses, adenoviruses, rhinoviruses and respiratory syncytial virus was established. An unusual shift of the period of maximum activity of respiratory syncytial virus to the 20th week was noted. Attention is paid to the need during the ongoing pandemic COVID-19 to fully immunize children as part of the National Immunization Calendar, also emphasized the role of mandatory annual vaccination against influenza. It is noted that the maximum protective effect of immunoprophylaxis of influenza acute and recurrent respiratory infections can be achieved with a combination of vaccination with bacterial lysates. The article presents a review of the literature and our data demonstrating the safety, good tolerability, and high clinical and immunological efficiency of polyvalent mechanical bacterial lysate for the prevention of acute and recurrent respiratory infections in children. It is shown that the use of polyvalent mechanical bacterial lysate during the prevaccination period makes it possible to substantially reduce the frequency of intercurrent infections, which reduces the number of temporary medical withdrawals and increases the coverage of vaccinations against influenza in organized groups to 85.1%. The role of trained immunity as one of the possible mechanisms providing nonspecific immunoprophylaxis during influenza vaccination and the use of bacterial lysates is discussed.

Histological study of the effect of bacterial lysates on the state of periodontal tissue in experimental periodontitis in rats

The aim of the research: to experimentally study at the histological and morphological level the degree of the corrective effect of bacterial lysate of the disturbed non-specific defense of the body on the model of periodontitis based on the Central Research Laboratory of the National University of Pharmacy. Materials and methods: prospective study has been conducted on experimental periodontitis in 42 rats for 90 days. The animals were treated with «Respibron» and the reference drug «Imudon». Histological and morphometric studies were carried out according to standard methods. Micropreparations were viewed under a Granum DCM 310 digital video camera. All interventions and euthanasia of animals were carried out in compliance with the European principles. Results: by the end of 90 days of experimental periodontitis at the local level in the homogenate of animal gum tissue compensatory mechanisms are depleted and differed from the norm by 397 times. The dynamics of the studied morphometric and histological parameters of "Respibron" was similar to the "Imudon", but the magnitude of destruction was less pronounced and differed at the end of the experiment by 17.2 times in comparison with the intact control, and in the control group the results improved by 23.1 times. Conclusion: the obtained data from the study indicate a high decompensation of experimental periodontitis. It is characterized by the formation of periodontal pockets and inflammatory bone loss. The magnitude of destruction differed from the norm by 397 times. Applying of bacterial lysates led to the compensation of bacterial dysbiosis, restoration of the tissues of paradont. The therapeutic effect of "Respibron" can be assessed as more powerful in comparison with "Imudon" in terms of the studied morphometric and histological parameters: the magnitude of improvement "Respibron" was 3.72 times higher than the indicators of "Imudon". We should continue the study of experimental periodontitis as mechanisms of development, protection, and restoration of tissues under conditions of pharmacological correction by bacterial lysate "Respibron"

Prospective Study in Children with Complicated Urinary Tract Infection Treated with Autologous Bacterial Lysates

Antimicrobial bacteria resistance is an important problem in children with recurrent urinary tract infections (rUTI), thus it is crucial to search for alternative therapies. Autologous bacterial lysates (ABL) may be a potential treatment for rUTI. Twenty-seven children with rUTI were evaluated for one year, urine and stool cultures were performed, 10 colonies of each culture were selected and those identified as Escherichia coli were characterized by serology. For patients who presented ≥105 UFC/mL, an ABL was manufactured and administered orally (1 mL/day) for a month. Twelve children were monitored for ≥1-year, 218 urine and 11 stool samples were analyzed. E. coli (80.5%) was the main bacteria isolated from urine and feces (72%). E. coli of classical urinary serotypes (UPEC), O25:H4, O75:HNM, and O9:HNM were identified in patients with persistent urinary infection (pUTI). In 54% of patients treated with ABL, the absence of bacteria was observed in urine samples after 3 months of treatment, 42% of these remained without UTI between 10–12 months. It was observed that the use of ABL controlled the infection for almost 1 year in more than 60% of the children. We consider it necessary to develop a polyvalent immunogen for the treatment and control of rUTI.

The role of immunomodulatory preparations in asthma treatment

Asthma remains one of the most prevalent respiratory tract disorders. The disease affects both adults and children and remains the most common cause of respiratory morbidity. Considering its significant impact on patients’ quality of life and the treatment burdened with side effects, a new therapy approaches affecting the clinical course of asthma are needed. Here we describe the current results that have been obtained on using immunomodulatory preparations in asthma. The analysis of previously published studies was conducted by using the PubMed and Scopus databases. Probiotics, bacterial lysates (BLs) and pidotimod are immunomodulatory compounds affecting both adaptive and innate immunity. The therapy based on probiotics might modulate the intestinal microbiota and regulate the inflammatory response. Bacterial lysates promote immune response by reversing Th1/Th2 unstable balance, which leads to reduction of allergen-induced airway hyperresponsiveness during asthma exacerbations. Pidotimod stimulates PRRs and increases the release of antimicrobial peptides which also leads to the improvement in the rate of respiratory tract infections. Some studies showed the beneficial effect of described preparations in asthma course. Regrettably, findings do not correspond with each other and the data referring to immunomodulatory compounds is still limited, thus there is an urgent need to conduct more, large sample studies.The conclusion we can only draw is that immunomodulatory compounds may offer an alternative approach for symptom reduction and prophylaxis against both infections and exacerbations of asthma.

Screening Collagenase Activity in Bacterial Lysate for Directed Enzyme Applications

Collagenases are essential enzymes capable of digesting triple-helical collagen under physiological conditions. These enzymes play a key role in diverse physiological and pathophysiological processes. Collagenases are used for diverse biotechnological applications, and it is thus of major interest to identify new enzyme variants with improved characteristics such as expression yield, stability, or activity. The engineering of new enzyme variants often relies on either rational protein design or directed enzyme evolution. The latter includes screening of a large randomized or semirational genetic library, both of which require an assay that enables the identification of improved variants. Moreover, the assay should be tailored for microplates to allow the screening of hundreds or thousands of clones. Herein, we repurposed the previously reported fluorogenic assay using 3,4-dihydroxyphenylacetic acid for the quantitation of collagen, and applied it in the detection of bacterial collagenase activity in bacterial lysates. This enabled the screening of hundreds of E. coli colonies expressing an error-prone library of collagenase G from C. histolyticum, in 96-well deep-well plates, by measuring activity directly in lysates with collagen. As a proof-of-concept, a single variant exhibiting higher activity than the starting-point enzyme was expressed, purified, and characterized biochemically and computationally. This showed the feasibility of this method to support medium-high throughput screening based on direct evaluation of collagenase activity.

Study of influence of bacterial lysate on cytokine indicators in experimental periodontis in rats

The aim of the research: to optimize the treatment of patients with a disturbed cytokine profile by a bacterial lysate in an experimental model of periodontitis against the background of changes in the local and systemic immune response. Materials and methods: prospective study has been conducted on experimental periodontitis in 42 rats for 90 days. The animals were treated by solution of «Respibron» and the reference drug «Imudon». The concentration of cytokines in the blood serum was determined by the enzyme immunoassay, circulating immune complexes – precipitation method is measured on a spectrophotometer, C-reactive protein – using a latex diagnosticum. All interventions and euthanasia of animals were carried out in compliance with the European principles. Results: the obtained data from the study indicate a high degree a state of decompensation of experimental periodontitis. An immuno-inflammatory reaction preceding periodontitis is accompanied by the disturbances of the cytokine balance, local and systemic immune response. Applying of bacterial lysates led to the compensation of bacterial dysbiosis, restoration of the balance of the activity of pro- and anti-inflammatory cytokines, and a decrease the hyperactivity of immunological markers. Conclusion: the studies carried out have shown that the use of bacterial lysate is a pathogenetically substantiated component of therapeutic tactics. The normalizing effect of the lysate on the parameters of the immune response and cytokine profile has been reliably shown. Considering the immuno-inflammatory reaction at the experimental periodontitis, accompanied by the cytokine imbalance, study the pharmacological correction by bacterial lysate should continue from the point of view of establishing the mechanisms of development, protection, and restoration of tissues. It has been proved that by the end of the 90-day period of observation of the course of experimental periodontitis, the power of natural compensatory mechanisms acquired a state of decompensation. It has manifested by increased pro-inflammatory cytokine IL-1β in 1.7 times, and TNF-α in 3 times, decreased anti-inflammatory cytokine IL-10 in 1.6 times; increased the concentration of CIC in the blood in 2 times, C-reactive protein in 4.4 times at the local level in the gum tissue homogenate of the control pathology group of animals. The powerful corrective effect of bacterial lysates «Respibron» and «Imudon» on the indicators of the cytokine series on the model of chronic experimental periodontitis has been reliably established. The normalizing effect is due to the compensation of bacterial dysbiosis, restoration of the balance of the activity of pro- and anti-inflammatory cytokines, and a decrease in the hyperactivity of immunological markers. The therapeutic effect of «Respibron» (bacterial lysate of 13 strains of microorganisms) can be assessed as expressive and more powerful in comparison with «Imudon». The obtained results make it possible to continue the study of the course of experimental periodontitis from the point of view of establishing the mechanisms of development, protection, and restoration of tissues under conditions of pharmacological correction with bacterial lysate «Respibron».