[Efficacy and safety of patients immunization with chronic obstructive pulmonary disease with monoclonal antibodies].

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by a high level of morbidity and mortality and is associated with significant social and economic damage to the health system and society. COPD and COVID-19 have many potentially negative relationships that can lead to worse outcomes of COVID-19, including impaired lung function, old age and the presence of concomitant diseases Aim. To assess efficacy and safety of the drug Tixagevimab + Cilgavimab for the pre-contact prevention of COVID-19 infection in patients with COPD. MATERIAL AND METHODS: A total of 324 male patients were included in the study, who were treated or monitored at the Regional Clinic Hospital №3 and the Regional Pulmonological Center of Chelyabinsk in April-May 2022. The main endpoints of observation, for 3 and 6 months, to assess the effectiveness were the dynamics of shortness of breath according to The Modified Medical Research Council Dyspnea Scale - mMRC, the The forced expiratory volume in 1 second, the number of exacerbations, emergency calls, hospitalizations, polymerase chain reaction for SARS-CoV-2. Local and general reactions after immunization were evaluated. The drug Evusheld (150 mg Tixsagevimab +150 mg Cilgavimab, AstraZeneca) was used for immunization. RESULTS AND CONCLUSION: The effectiveness of pre-contact prevention of COVID-19 was 88.8%. The administration of the drug does not provoke an exacerbation of the underlying disease. The main clinical and functional indicators have positive dynamics by the 6th month of follow-up. The drug is well tolerated and has no significant both early and late complications.

[Analysis of the clinical efficacy of vaccination against pneumococcal infection in patients with chronic obstructive pulmonary disease in combination with type 2 diabetes mellitus].

The article presents data on the analysis of the clinical efficacy of vaccination against pneumococcal infection in patients with chronic obstructive pulmonary disease (COPD) in combination with type 2 diabetes mellitus during a 5 years follow-up period. MATERIALS AND METHODS: The study included patients (n=103) with COPD in combination with type 2 diabetes. Primary endpoints were changes dyspnea mMRC score, FEV1, number of exacerbations of COPD, hospitalizations, and a rate of pneumonia. The prognostic indices BODE, DOSE, ADO were also calculated. 13-valent conjugate pneumococcal vaccine PCV-13 and 23-valent polysaccharide vaccine PPV-23 were used for vaccination. RESULTS: It has been established that when vaccination is included in the management plan for patients with COPD in combination with diabetes, the severity of dyspnea decreases, the lung function stabilize both for short-term and 5-years follow-up. Vaccination with PCV-13 and PPV-23 reduce number of exacerbations, a rate of pneumonia and hospitalizations, but long-term efficacy has been demonstrated only for PCV-13. Vaccination with PCV-13 can improve the quality of life and prognosis for patients with COPD in combination with type 2 diabetes. CONCLUSION: Vaccination of pneumococcal infection in patients with COPD and type 2 diabetes mellitus can reduce the number of exacerbations, incidence of pneumonia and the number of hospitalizations, improve the prognosis and survival of patients using PCV-13 by maintaining efficacy for 5 years of follow-up.

Sigma-1 Receptor Ligands Chlorpromazine and Trifluoperazine Attenuate Ca2+ Responses in Rat Peritoneal Macrophages.

Sigma-1 receptors are ubiquitous multifunctional ligand-regulated molecular chaperones in the endoplasmic reticulum membrane with a unique history, structure, and pharmacological profile. Sigma-1 receptors bind ligands of different chemical structure and pharmacological action and modulate a wide range of cellular processes in health and disease, including Ca2+ signaling. To elucidate the involvement of sigma-1 receptors in the processes of Ca2+ signaling in macrophages we studied the effect of sigma-1 receptor ligands, phenothiazine neuroleptics chlorpromazine and trifluoperazine, on Ca2+ responses induced by inhibitors of endoplasmic Ca2+-ATPases thapsigargin and cyclopiazonic acid, as well as by disulfide-containing immunomodulators Glutoxim and Molixan in rat peritoneal macrophages. Using Fura-2AM microfluorimetry we showed for the first time that chlorpromazine and trifluoperazine inhibit both phases of Ca2+ responses induced by Glutoxim, Molixan, thapsigargin, and cyclopiazonic acid in rat peritoneal macrophages. The data obtained indicate the participation of sigma-1 receptors in a complex signaling cascade caused by Glutoxim or Molixan and leading to an increase in intracellular Ca2+ concentration in macrophages. The results also indicate the involvement of sigma-1 receptors in the regulation of store-dependent Ca2+entry in macrophages.

Amplification of elliptically polarized sub-femtosecond pulses in neon-like X-ray laser modulated by an IR field.

Amplification of attosecond pulses produced via high harmonic generation is a formidable problem since none of the amplifiers can support the corresponding PHz bandwidth. Producing the well defined polarization state common for a set of harmonics required for formation of the circularly/elliptically polarized attosecond pulses (which are on demand for dynamical imaging and coherent control of the spin flip processes) is another big challenge. In this work we show how both problems can be tackled simultaneously on the basis of the same platform, namely, the plasma-based X-ray amplifier whose resonant transition frequency is modulated by an infrared field.

[Impact of vaccination with pneumococcal vaccines on recurrent pneumonia in patients with chronic obstructive pulmonary disease].

BACKGROUND: Community-acquired pneumonia (САР) and chronic obstructive pulmonary disease (COPD) are among the main causes of mortality worldwide, and, in addition, they also lead to great economic losses for the health system of all countries. Currently, there is an increase in cases of recurrent pneumonia, both in the general population and, in particular, in patients with COPD. One of the most important risk factors for the development of pneumonia is the previous episode of САР. Potential risk factors for recurrent pneumonia are concomitant diseases such as heart failure, COPD, diabetes mellitus, neurological disorders, swallowing dysfunction, immune deficiency. AIM: To conduct a retrospective analysis of the effect of vaccine prophylaxis with conjugated pneumococcal vaccine (PCV13) and polysaccharide pneumococcal vaccine (PPV23) on the risk of recurrent pneumonia in patients with COPD. MATERIALS AND METHODS: A total of 302 male patients were included in the retrospective study. When analyzing the data, the fact of the development of pneumonia of any etiology during the 5th observation period was taken into account. For the recurrence of pneumonia, more than two episodes of CAP were taken during the year. 13-valent conjugated pneumococcal vaccine Prevenar-13 and 23-valent polysaccharide vaccine Pneumo23 were used for vaccine prophylaxis. The relative risk of the event was calculated. A 95% confidence interval was used. RESULTS AND CONCLUSION: A retrospective analysis showed that, firstly, CAP is a fairly frequent complication of COPD: initially, the average percentage of cases of САР was 19.3%. Secondly, the risk of developing repeated episodes of pneumonia remains quite high in unvaccinated patients and tends to increase within 5 years: from 17 to 22%. Thirdly, the pneumococcal vaccines used have different effects on the risk of recurrent pneumonia in patients with COPD, a significant decrease in the number of recurrent pneumonia is observed only with the use of conjugated vaccines.

Acoustically induced transparency for synchrotron hard x-ray photons.

The induced transparency of opaque medium for resonant electromagnetic radiation is a powerful tool for manipulating the field-matter interaction. Various techniques to make different physical systems transparent for radiation from microwaves to x-rays were implemented. Most of them are based on the modification of the quantum-optical properties of the medium under the action of an external coherent electromagnetic field. Recently, an observation of acoustically induced transparency (AIT) of the 57Fe absorber for resonant 14.4-keV photons from the radioactive 57Co source was reported. About 150-fold suppression of the resonant absorption of photons due to collective acoustic oscillations of the nuclei was demonstrated. In this paper, we extend the AIT phenomenon to a novel phase-locked regime, when the transmitted photons are synchronized with the absorber vibration. We show that the advantages of synchrotron Mössbauer sources such as the deterministic periodic emission of radiation and controlled spectral-temporal characteristics of the emitted photons along with high-intensity photon flux in a tightly focused beam, make it possible to efficiently implement this regime, paving the way for the development of the acoustically controlled interface between hard x-ray photons and nuclear ensembles.

[Long-term postoperative outcomes in patients with cicatricial tracheal stenosis depending on surgical approach]. / Otdalennye rezul'taty lecheniya rubtsovogo stenoza trakhei v zavisimosti ot varianta rekonstruktsii.

OBJECTIVE: To analyze the long-term postoperative outcomes in patients with cicatricial tracheal stenosis and to determine the indications for various surgical strategies. MATERIAL AND METHODS: There were 976 patients with benign cicatricial tracheal stenosis for the period 2001-2017. Tracheal stenosis occurred after mechanical ventilation and tracheostomy in 910 (93.2%) patients. Other causes were neck trauma, burns, previous surgery or tuberculosis. Idiopathic stenosis was observed in 41 (4.2%) patients. Multiple-stage reconstructive treatment was possible due to benign nature of disease. There were 2.4 operations per a patient, and 976 patients underwent 2327 procedures. Circular tracheal resection was preferred (n=396). RESULTS: Surgical complications occurred in 107 (4.6%) cases, mortality rate - 0.3%. In long-term period, 42 patients died for various causes. In most cases (n=34, 80.9%), mortality was associated with concomitant diseases or consequences of trauma rather cicatricial tracheal stenosis or its treatment. Eight patients died from cicatricial tracheal stenosis or its treatment (7 patients after staged repair, 1 after circular tracheal resection). Four patients died due to asphyxia following T-tube obturation with a tracheobronchial secret or unjustified decannulation. For various reasons, 41 (6.2%) patients continued their treatment in other hospitals (4 patients died). Mortality rate in this group was 9.8%. Favorable long-term outcome was observed in 90.1% of patients, good and unsatisfactory results - in 7.2% and 1.8% of patients, respectively. Circular tracheal resection ensured better functional outcome. CONCLUSION: Surgical treatment of cicatricial tracheal stenosis is associated with low incidence of postoperative complications and mortality. However, further improvement in long-term results is associated with advanced rehabilitation programs for concomitant diseases. Treatment of cicatricial tracheal stenosis should be carried out at specialized hospitals.

[Experience of using dupilumab in the treatment of severe asthma].

The article provides data on modern approaches to the treatment of patients with severe uncontrolled bronchial asthma with an emphasis on the use of dupilumab, a human recombinant monoclonal antibody to the alpha subunit of the interleukin (IL)-4 receptor, which inhibits signal transmission from both IL-4 and IL-13. The results of dupilumab pivotal randomized clinical trials DRI12544, QUEST and VENTURE are summarized. Indications for use of this medicinal product are listed in Federal Clinical Guidelines on the management of asthma (year of revision 2019). Clinical cases with various clinical course of bronchial asthma are described, including cases with frequent exacerbations. In conclusion, dupilumab could be a treatment of choice for the patients with severe bronchial asthma and it is reasonable from an economic, clinical and pathogenetic point of view.

Neuroleptic Chlorpromazine Modulates Ca2+ Responses in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor antagonist neuroleptic chlorpromazine significantly inhibits glutoxim- and molixan-induced Ca2+ responses and Ca2+ responses induced by endoplasmic reticulum Са2+-ATPase inhibitors thapsigargin and cyclopiazonic acid in rat peritoneal macrophages. The results suggest the involvement of sigma-1 receptors in the signaling cascade induced by glutoxim or molixan and leading to intracellular Ca2+ concentration increase and in the regulation of store-dependent Ca2+ entry in macrophages.

[Experience of olokizumab use in COVID-19 patients].

Most subjects with the COVID-19 experience mild to moderate symptoms, but approximately 10% of cases suffer from severe course of disease. IL-6 inhibitors are actively used to neutralize and prevent the cytokine storm. Olokizumab is a humanized monoclonal antibody belonging to the G4/Kappa immunoglobulin isotype that selectively binds to human IL-6 and effectively neutralizes it. AIM: To evaluate the efficacy and safety of Artlegia (olokizumab) for the treatment of subjects with a disease caused by the SARS-COV-2 virus in a real-world clinical setting. MATERIALS AND METHODS: The analysis included data of 610 subjects aged 55.0812.68 years who received olokizumab at a single dose of 160 mg/mL 0.4 mL subcutaneously as a preemptive anti-inflammatory therapy. The comparison group included 511 subjects aged 55.2311.23 years who received standard therapy without IL-6 inhibitors. Control Endpoints: 1. Positive clinical changes on Day 7. 2. Changes in the CRP levels on Days 1, 2, and 7. 3. Duration of oxygen therapy. 4. Number of days in hospital. 5. Number of adverse events. 6. Disease outcome. RESULTS: If a cytokine storm occurs, immune regulatory events will trigger the development of either a protective immune response or an exacerbated inflammatory response. The use of preemptive anti-inflammatory therapy has both a short-term and, most importantly, a long-term effect on the T and B parts of the immune process. These aspects definitely require further research and observation. CONCLUSION: The use of olokizumab to treat the new COVID-19 coronavirus disease has demonstrated a positive effect on clinical and laboratory parameters. Primarily, it affects the severity of clinical parameters by improving the general condition already on the first day of observation, and decreasing body temperature to normal values. The changes in the C-reactive protein levels show a significant effect of the IL-6 inhibitor on the systemic inflammatory response.

Sigma-1 Receptor Agonist Amitriptyline Inhibits Store-Dependent Ca2+ Entry in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor agonist-tricyclic antidepressant amitriptyline-significantly inhibits store-dependent Ca2+ entry, induced by endoplasmic Ca2+-ATPase inhibitors thapsigargin and cyclopiazonic acid, in rat peritoneal macrophages. The results suggest a possible involvement of sigma-1 receptors in the regulation of store-dependent Ca2+ entry in macrophages.

SUPPORT TOOL FOR DECISION-MAKING IN SELECTING CHEMOTHERAPY TACTICS FOR TREATMENT OF BREAST CANCER PATIENTS.

Breast cancer (BC) is the most commonly occurring oncologic disease in women over the world. The introduction of modern methods of diagnostics and treatment of BC patients allowed achieving some success in the disease control. Chemotherapy (CT) is one of the most effective treatments for BC patients, but the individualization of the choice of effective treatment regimens remains an unresolved issue. Aim of the study: to develop approaches to enhance the effectiveness of treatment of BC patients following the levels of circulating serum miRNAs, which are associated with sensitivity to polychemotherapy. Basing on the analysis of literature data we selected the pattern with 10 miRNAs (200с, 205, 30а, 155, 25-3p, 27а, 663, 335, 139-5р, and 497), circulating in blood serum, as markers of sensitivity/resistance of breast tumors to chemotherapy. A mathematic model was developed to estimate the effectiveness of the standard CT regimens basing on the level of expression of chosen miRNAs. Experimental verification of mathematic model performance was provided with Fortran 2018 program complex. We developed a tool of decision-making support for oncologists that may significantly facilitate the development of the CT tactics in BC patients at the stage of selection of effective CT regimen. The developed mathematic model may serve as a basis for scheduling of effectiveness prognosis of certain polychemotherapy regimens in an individual patient.

Sigma-1 Receptor Antagonists Haloperidol and Chlorpromazine Modulate the Effect of Glutoxim on Na+ Transport in Frog Skin.

Using voltage-clamp technique, the involvement of sigma-1 receptors in the regulation of Na+ transport in frog skin by the immunomodulatory drug glutoxim was investigated. We have shown for the first time that preincubation of the frog skin with the sigma-1 receptor antagonists haloperidol and chlorpromazine attenuates the stimulatory effect of glutoxim on the Na+ transport. The results suggest the possible involvement of the sigma-1 receptors in the regulation of Na+ transport in frog skin epithelium by glutoxim.

[Analysis of the impact of vaccination of pneumococcal infection in patients with chronic obstructive pulmonary disease in combination with diabetes].

AIM: The article presents data on the evaluation of the clinical efficacy of using a conjugated pneumococcal vaccine in patients with COPD in combination with 2-type diabetes during a 3-year follow - up period. MATERIALS AND METHODS: The study included 309 patients with an isolated course of COPD and in combination with diabetes. The main parameters for evaluating the effectiveness were: the dynamics of clinical symptoms - shortness of breath on the mMRC scale, CAT test, FEV1, the number of exacerbations, hospitalizations, the number of pneumonia, the state of carbohydrate metabolism (HbA1c) and the lipid profile. For vaccine prevention 13-valent conjugated pneumococcal vaccine Prevenar-13 was used. RESULTS AND CONCLUSIONS: The use of PСV13 helps to reduce the severity of respiratory symptoms, reduce the number and duration of exacerbations of COPD, reduce the number of pneumonia. Both in isolated course of COPD and in combination with diabetes. Vaccination PCV13 in patients with comorbid course contributes to the compensation of carbohydrate metabolism and improve the lipid profile.

[Analysis of the effectiveness of joint or sequential vaccination with pneumococcal and influenza vaccines in patients with chronic obstructive pulmonary disease].

One of the extremely important problems of managing patients with chronic obstructive pulmonary disease (COPD) is to prevent exacerbations. The article presents data on the clinical and economic efficiency of joint vaccine prevention of conjugate pneumococcal vaccine Prevenar 13 (PCV13) and SOVIGRIPP flu vaccine in patients with COPD. MATERIAL AND METHODS: 153 patients were included in the study. They were divided into three groups. The first group (n=53) - consisted of patients who were vaccinated with PCV13. The second group (n=51) included patients who were vaccinated with PCV13 and influenza vaccine simultaneously or with an interval of not more than 2 weeks. The third group (n=49) included not vaccinated patients. The observation period is 1 year. RESULTS AND DISCUSSION: Combined vaccine prevention of pneumococcal conjugate and influenza vaccines reduces the degree of clinical impairment and stabilizes the main functional parameters of the respiratory system at a significantly lower level compared to monovaccination with only pneumococcal vaccine. Single - stage vaccination with PCV13 and influenza vaccine reduces the risk of adverse events in COPD, reduces the number of exacerbations associated with this hospitalization of patients and the incidence of pneumonia. CONCLUSION: Combined vaccination with the use of two vaccines minimizes the costs of the health care system. The budget savings can reach an average of 80-83% per year or up to 26 967 - 28 001 rubles per patient with COPD.

Attosecond Pulse Amplification in a Plasma-Based X-Ray Laser Dressed by an Infrared Laser Field.

High-harmonic generation (HHG) of laser radiation has led to attosecond pulse formation which offers unprecedented temporal resolution in observing and controlling electron and nuclear dynamics. But the energy of attosecond pulses remains quite small, especially for photon energies exceeding 100 eV, which limits their practical applications. We propose a method for amplification of attosecond pulses in the active medium of a plasma-based x-ray laser dressed by a replica of the laser field used for HHG. The experimental implementation is suggested in hydrogenlike C5+ x-ray laser at 3.4 nm wavelength in the "water window" range.

Amitriptyline Attenuates Ca2+ Responses Induced by Glutoxim and Molixan in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that sigma-1 receptor agonist, tricyclic antidepressant amitriptyline, significantly inhibits glutoxim- and molixan-induced Ca2+-responses in rat peritoneal macrophages. The results suggest possible involvement of sigma-1 receptors in the signaling cascade induced by glutoxim or molixan and leading to intracellular Ca2+ concentration increase in macrophages.

Epoxygenase Inhibitors Attenuate the Stimulatory Effect of Glutoxim on Na+ Transport in Frog Skin.

Using voltage-clamp technique, the involvement of epoxygenases in immunomodulatory drug glutoxim regulation of Na+ transport in frog skin was investigated. We have shown for the first time that preincubation of the frog skin with epoxygenase inhibitors econazole or proadifen almost completely inhibits the stimulatory effect of glutoxim on Na+ transport. The data suggest the involvement of the enzymes and/or products of epoxygenase oxidation pathway of arachidonic acid metabolism in glutoxim effect on Na+ transport in frog skin epithelium.

Sigma-1 Receptor Antagonist Haloperidol Attenuates Store-Dependent Ca2+ Entry in Macrophages.

Using Fura-2AM microfluorimetry, we have shown for the first time that preincubation of macrophages with sigma-1 receptor antagonist haloperidol leads to a significant inhibition of the store-dependent Ca2+ entry induced by endoplasmic Ca2+-ATPase inhibitors thapsigargin or cyclopiazonic acid in rat peritoneal macrophages. The results suggest the involvement of the sigma-1 receptor in the regulation of storedependent Ca2+ entry in macrophages.

Phospholipase A2 Inhibitors Modulate the Effect of Trifluoperazine on the Intracellular Ca2+ Concentration in Macrophages.

Using Fura-2AM microfluorimetry, it was shown for the first time that phospholipase A2 inhibitors 4-bromophenacyl bromide and glucocorticosteroids prednisolone and dexamethasone attenuate Ca2+ responses induced by neuroleptic trifluoperazine in macrophages. The results suggest the involvement of phospholipase A2 and arachidonic acid metabolism cascade in the effect of trifluoperazine on intracellular Ca2+ concentration in macrophages.