In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2.

The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 µM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.

[Analysis of current diagnostic and treatment approaches for acute rhinosinusitis according polyclinics data of the outpatient service of Administrative Directorate of the President of the Russian Federation]. / Analiz sovremennykh skhem diagnostiki i lecheniya ostrogo rinosinusita po dannym ambulatornoi sluzhby poliklinik Upravleniya delami Prezidenta RF.

Acute rhinosinusitis is one of the most common outpatient diseases. The duration of antibiotic therapy in practice can be a cause of disagreement. The latest European guideline for rhinosinusitis EPOS 2020 does not specify clear terms for antibacterial therapy for acute bacterial rhinosinusitis, which suggests that they are determined by the attending physician based on the rate of regression of clinical manifestations in each specific clinical case. OBJECTIVE: To analyze the treatment regimens of adult patients with acute rhinosinusitis in the system of the outpatient service of Administrative Directorate of the President of the Russian Federation in Moscow and compare these schemes with guidelines. MATERIAL AND METHODS: A retrospective analysis of 2267 outpatient disease histories of patients who were on outpatient treatment with a diagnosis of acute rhinosinusitis treated by otorhinolaryngologists from 7 ambulance clinics for the period from January 2016 to May 2018 was performed. Diagnostic methods and treatment regimens of these patients were evaluated. RESULTS: At the diagnostic stage, X-ray methods were recommended in 87% of cases, and ultrasound examination of the paranasal sinuses was performed in 4% of cases. Elimination and irrigation therapy was prescribed in 88.05% of cases (1996 people), maxillary sinus punctures were performed in 9.82% of cases, the average number of procedures was 2±1.3, treatment by displacement was performed in 31.8% of patients, the average number of procedures was 3±1.2. Antibiotic therapy was recommended in 77.4% of cases (1755 people), penicillin group drugs were prescribed in 41.5% of cases, macrolides in 30.5% of cases, cephalosporins in 20.7% of cases, and fluoroquinolones in 7.3% of cases. Intranasal glucocorticosteroids were submitted by 67.7% of patients (1535 people), mucolytics and mucoregulatory drugs - 41% of patients, decongestants for acute rhinosinusitis were recommended in 60.9% of cases, antihistamines - in 36.8% of cases. An average course of antibacterial therapy was 5.9±1.34 days, the recovery of the patients was observed on the background of complex treatment. CONCLUSIONS: In general, in the system of the outpatient service of Administrative Directorate of the President of the Russian Federation, diagnostic and therapeutic measures are carried out in accordance with current clinical recommendations. There is a fairly high percentage of prescribing macrolides (30.5%) and fluoroquinolones (7.3%) in starting therapy, which is a violation of the principles of starting antibacterial therapy.

[The effectiveness of local therapy of acute inflammatory diseases of the upper respiratory tract]. / Éffektivnost' lokal'noi terapii pri ostrykh vospalitel'nykh zabolevaniiakh verkhnikh dykhatel'nykh putei.

Acute bacterial rhinosinusitis (ABRS) is one of the most common diseases in outpatient practice with a steady tendency to increase of complicated forms in recent years. The risk of antibiotic resistance makes it necessary to search for effective pathogenetic methods of ABRS treatment. OBJECTIVE: To evaluate the efficacy of inhalation therapy with compressor nebulizer using Fluimucil Antibiotic IT in the treatment of ABRS and acute laryngotracheitis in outpatient practice. MATERIAL AND METHODS: Patients with ABRS were divided into two sex- and age-matched groups of 26 people each. The first group was treated with 250 mg of Fluimucil Antibiotic IT inhalations by the use of Norditalia HI-NEB compressor nebulizer once a day. The second group was treated with amoxicillin/clavulanate 875 mg + 125 mg orally two times a day. RESULTS: In the first group, the cough disappeared significantly earlier (on day 5-6) than in the second group (on day 7-8). In the first group, nasal congestion also disappeared significantly earlier (on day 3-5) than in the second group (on day 4-6). There was no significant difference in the reduction of intoxication syndrome and nasal secretions in both groups. CONCLUSION: Local antibacterial and mucolytic therapy in the initial stages of ABRS and acute laryngotracheitis reduces rhinological symptoms and coughing, similar to systemic antibacterial therapy. The use of Fluimucil Antibiotic IT in the early stages of the treatment provides an opportunity to avoid systemic antibiotics, which reduces the risk of antibiotic resistance as well as side effects in patients.

[An analysis of experience of using nasal catheters in acute bacterial rhinosinusitis]. / Analiz opyta primeneniya nazal'nykh kateterov pri ostrom bakterial'nom rinosinusite.

The number of cases of acute bacterial rhinosinusitis (ABRS) in our country tends to increase. According to clinical guidelines of the Ministry of Health of the Russian Federation, nasal catheter drainage is used to treat ABRS, but not all ENT-doctors use this method in daily practice. Many of them use it empirically and obtain good results. GOAL: To study the experience of ENT-doctors using the YAMIK nasal catheter (NC) in their clinical practice. MATERIAL AND METHODS: To achieve the goal, a 16-question questionnaire was developed. Further, a survey of 30 ENT-doctors was conducted via e-mail. RESULTS AND DISCUSSION: The study showed a marked dispersion of data regarding the time of starting therapy, the number of necessary procedures, as well as the components of medication solutions administered to the paranasal sinuses. At the same time, the effectiveness of the method, in doctors' opinion, is very high (above 90%). The incorrect technique of NC application, absence of studies according to the principles of Good Clinical Practice (GCP), and constructive disadvantages of NC may be probable reasons for the method undervaluation. CONCLUSIONS: The prescription of procedures with NC to patients with ABRS is empirical and is probably related to the absence of clear indications for such treatment, data on its duration, and associated therapy. Consequently, research following GCP principles is required to develop an algorithm for treating ABSR with an NC. The development of a new design for an NC that will allow each ENT-doctor to learn the method is also appropriate.

[The rhinological simulator: the upgrade and validation study with the evaluation of the effectiveness of its application]. / Rinologicheskii simuliator: modernizatsiia i otsenka éffektivnosti primeneniia.

The objective of the present study was to upgrade the rhinological simulator employed as a tool for the teaching of the basic technical skills in endoscopic sinus surgery (ESS). The new ESS simulator providing a model of the nasal cavity consists of the replaceable cylinders and the adaptable table stand. It includes a set of 3D printed nasal models. Each of them is the elliptical tube of a specific size. The participants of the study performed different tasks depending on the structural properties of the tubes. A wide variety of surgical instruments and esndoscopes could be fitted to the simulator. 16 otorhinolaryngologists having no previous experience with ESS were recruited into the study to evaluate the effectiveness of the training procedures. After a brief tutorial, the participants practiced an one hour-long exercise per day during 5 days. The pre-training and post-training performances were videotaped. The task-performance time and the number of technical errors made by the operators were estimated immediately before and after the training session. To assess the subjective attitudes of the operators toward the new technology, the participants of the study were asked to complete the model questionnaire soon after the termination of the training course. The questionnaire contained 34 items. The correctness of the answers was assessed based on the 5-point Likert scale, with score 1 meaning 'totally disagree' and score 5 - 'totally agree'. The statistically significant reduction of the performance time and the number of technical mistakes was documented within the first 5 hours after the onset of teaching (p<0.05) which suggests the effectiveness of the training procedures. The questionnaire study has demonstrated the positive attitude of the trainees toward the proposed technology. The average score based on the Likert scale was higher than 3 for all kinds of questions. It is concluded that the results of this study give evidence of the positive assessment of the upgraded rhinological simulator as an effective tool for the teaching of the basic skills necessary to operate various surgical instruments and endoscopes by the novice surgeons in the field of endoscopic sinus surgery .

[A study of the efficacy and safety of new cephalosporin in the treatment of acute bacterial rhinosinusitis]. / Izuchenie effektivnosti i bezopasnosti novogo tsefalosporinovogo antibiotika pri lechenii ostrogo bakterial'nogo rinosinusita.

Acute rhinosinusitis is leading in frequency of antibiotic prescribing all over the world. At the same time the problem of antibiotic resistance and safety of antimicrobial drugs becomes more relevant and international. The article describes the basic mechanisms of bacterial resistance and growth of side effects when using macrolides, respiratory fluoroquinilones and ß-lactam antibiotics of different types. Formation of IgE-mediated cephalosporin allergy is associated with the side R1 chain. The R1 structure of cephalosporins I and II generations is similar to penicillins, thus creating conditions for cross-allergy progression. R1 of cephalosporins III and IV generations is represented by a qualitatively different chemical compound (aminothiazol-oxime group) that increases the level of tolerance to these antibiotic types. The data of surveillance study are given to evaluate the efficacy and safety of the new drug Spectracef (active substance is cephalosporin of III generation Cefditoren) when treating acute bacterial rhinosinusitis on an outpatient basis.

[TREATMENT OF PATIENTS WITH CHRONIC RECURRENT HERPES VIRUS INFECTION OF GENITAL LOCALIZATION: A CLINICAL STUDY OF FORTEPREN PREPARATION].

AIM: Selection of optimal dosage regimen, length of treatment course (frequency of administration), safety, tolerance and clinical effectiveness evaluation of the medical preparation fortepren in patients with chronical recurrent herpes virus infection of genital localization. MATERIALS AND METHODS: The medical product of antiviral and immune modulating effect--fortepren (sodium polyprenyl phosphate) as a 4 mg/ml solution for injections combined with the base course of acyclic nucleoside acyclovir, 400 mg tablets, held studies. 40 male and female patients participated in the study. After a 10-day acyclovir course (400 mg x 3 times a day) for removing the acute phase, 4 groups of 10 individuals were formed: 1--5 ml (20 mg) of fortepren i/m once at day 13 ± 2 after the start of the study after the completion of the treatment of the acute phase of the disease; 2--5 ml (20 mg) fortepren i/m 3 times at an interval of 21 days; 3--2 ml (8 mg) fortepren i/m 3 times at an interval of 21 days; 4 (control)--5 ml of placebo i/m at remission stage 3 times at an interval of 21 days. Increase of the duration of inter-recurrence period, decrease of the severity of the recurrences, state of skin and mucous damage elements, improvements of immunologic parameters were considered during effectiveness evaluation. RESULTS: Significant differences in the frequency of recurrences of genital herpes were shown for 3 months of observation in experimental and control groups. A significant reduction of genital herpes recurrence frequency from 3.52 ± 0.09 (before treatment) to 2.89 ± 0.08 (after treatment) was noted in patients of group 3 (p < 0.001). The frequency of recurrences in the control group was 3.84 ± 0.10, that was higher than the parameters in all the experimental groups. A significant reduction of the rash area was noted in group 3, moreover, a redution of frequency of detection of clinical manifestations of genital herpes in the form of vesicle elements after treatment in groups 2 (p = 0.02) and 3 (p = 0.005) was found. Evaluation of local symptoms has established that burning have caused minimal discomfort for patients of groups 3 and 4 and itch and soreness--of groups 1 and 3. The least pronounced exacerbations were noted in patients of group 3. Intramuscular administration of fortepren preparation was established to result in the increase of titers of leukocyte virus-induced interferon for the whole duration of treatment. CONCLUSION: An intramuscular dose of 2 ml (8 mg) at recurrence stage 3 times at an interval of 21 days after the completion of the 10-day base course of treatment of the acute phase of chronical recurrent herpes virus infection of genital localization using acyclovir was accepted as an optimal dosage regimen. Analysis of the obtained results has shown an acceptable safety profile and a good level of tolerance for fortepren preparation.

[Chronic rhinosinusitis with nasal polyps. The recent trend in the studies of the pathogenesis, diagnosis and treatment of this disease]. / Polipoznyi rinosinusit. Sovremennye podkhody k izucheniiu patogeneza, diagnostike i lecheniiu.

A review of the current problems of nasal polyposis has been presented. The results of an analysis mainly of foreign literature have been given, which is reflected in EPOS 2012.

[Acute rhinosinusitis: diagnostics and treatment].

Acute rhinosinusitis is a challenging clinical problem due to its high prevalence. The overwhelming majority of the cases of acute rhinosinusitis (ARS) have viral etiology. Clinical manifestations of viral and bacterial rhinosinusitis can be very similar. Similar expert communities have proposed their recommendations on diagnostics and treatment of acute rhinosinusitis in the recent decade. These recommendations are underlain by the principles of evidence-based medicine, take into consideration the result of reliable investigations, and reflect the opinions of leading specialists in otorhinolaryngology, allergology and immunology. The present review contains the analysis of consensus documents and recommendations. The results of ongoing research provide convincing evidence of the effectiveness of intranasal application of corticosteroids in the patients presenting with acute rhinosinusitis. Antibacterial therapy of acute rhinosinusitis is indicated only in the case of severe or complicated clinical course of the disease.

[Medicamental rhinitis. The new possibilities for its conservative treatment].

The objective of the present study was to estimate the efficacy, safety, and tolerability of protracted therapy with sinuforte for 15 days in 40 patients presenting with medicamental rhinitis (MR). The secondary objective was to evaluate the long-term results of this treatment. The results of the study indicate that the efficacy of sinuforte therapy in the patients using nasal decongensants during 12 months amounts to 80.7%. This observation gives reason to recommend sinuforte as the product of choice for the treatment of the patients with medicamental rhinitis.

[Application of three-dimensional computer models of the nose in rhinology].

A new computer program has been developed designed to simulate all possible variants of nasal septum deformation and anatomical malformation of turbinate bones. Moreover, the program makes it possible to analyse approaches to surgical correction of these problems. Implications of this model for the practical treatment of patients with these disorders are discussed. The program provides a qualitatively new tool for obtaining a deeper insight into a given surgical intervention and facilitates mutual understanding between the surgeon and the patient. Also, it may be used as a teaching aid in the training of young ENT specialists.

[Effect of nasal decongestants on locomotor activity of the ciliary apparatus of nasal mucosa in patients with acute purulent rhinosinusitis].

The present work was designed to evaluate the influence of certain nasal decongestants (oxymethazoline hydrochloride and oxymethazoline hydrochloride used in combination with eucalyptol) for the treatment of acute purulent rhinosinusitis. Results of the study give evidence of high therapeutic effectiveness of these preparations. It for the first time provided exact data on locomotor activity of the ciliary apparatus of nasal mucosa in the periods of exacerbation and during reconvalescence after the disease.

[Otoendoscopy for the diagnosis of chronic middle ear diseases].

The objective of the present work was to evaluate potential of otoendoscopy for the diagnosis of chronic middle ear diseases. A total of 195 patients (274 ears) with this pathology were examined. The group included 87 men (114 ears) and 108 women (160 ears) aged from 16 to 72 (mean 43.5) years. All of them underwent rigid video-otoendoscopy. The proposed method is suitable for the use in outpatient clinics with the help of endoscopes 4.0 and 2.7 mm in diameter and an angle of vision 0 and 30 degrees respectively. Analysis of the results of the study was used to develop criteria for the evaluation of the endoscopic picture. The study allowed the agreement between the diagnoses established before and after otoendoscopic examination to be estimated and expressed in percentage terms. It is concluded that the above diagnostic algorithm of otoendoscopy permits to evaluate and systematize results of otoendoscopic examination and to make decision on the necessity of referring the patient for further treatment in a hospital.

[Mucociliary transport and motility of the ciliary system of the nasal mucosa in patients with chronic polypous rhinosinusitis].

A transport function and motor activity of the ciliary system (MACS) of the nasal mucosa was studied in 10 patients with chronic polypous rhinosinusitis (CPRS). A complex examination included optic endoscopy of the nasal cavity for assessment of nasal polypous process, timing of the saccharine test (ST) according to standard technique, and ciliary beat rate (BR) by V.S. Kozlov method. For estimation of ciliary BR epithelium was taken from five zones: inferior and middle turbinated bones, nasal septum, base and top of the polyp growing from the median nasal passage. ST time in CPRS is much higher (28.3+/-0.34 min) than normal age-specific values. Ciliary BR in different nasal anatomic zones in CPRS is not similar. MACS on the inferior turbinated bone and nasal septum was absent, none of the samples contained cells with functioning cilia. Ciliary BR remained rather high, despite the pathological process, at the site of the top and base of the polyps as well as on the middle turbinated bone (8.7+/-1.07, 8.1+/-1.02, 6.5+/-0.35 Hz, respectively).

[Effects of different temperatures of saline and isotonic saline solution on changes in functional characteristics of the nasal cavity].

The influence of different temperatures (22 degrees capital ES, Cyrillic, 30 degrees capital ES, Cyrillic, 37 degrees capital ES, Cyrillic) of 2% saline solution and isotonic saline solution on the breathing function of the nasal cavity and transport function of the nasal mucosa in nasal shower with these solutions was studied in healthy volunteers. Nasal shower technique with application of the device Rhinolife is described. It was found that nasal shower with isotonic saline solution at temperature of 37 degrees C is optimal as it does not depress a nasal breathing function and is comfortable for the patient.

[A nasal cycle in healthy children].

A nasal cycle was studied in 10 healthy children (5 boys and 5 girls) aged 11-17 years (mean age 14.1+/-1.9 years). Registration of the nasal cycle was conducted for 7 hours by means of long-term nasal monitoring with Rhinocycle rhinoflowmeter (Interacoustics, Denmark). The nasal cycle was presented as a graphic image of fluctuations of a relative volumetric flux (RVF) in the relative units in accordance with linear dependence of pressure in the air flow to its volume. The nasal cycle in all healthy children was irregular, with mean fluctuation rate 1.3+/-0.6 h. There were no significant differences by RVF between the right and left parts of the nose in 8 children. In girls the nasal cycle most often was partially coinsiding, partially fluctuating while in most boys (in 4 of 5) the nasal cycle was irregular bilateral and fluctuating. It was found that the cycle was not longer or regular with the child's growth.

[Bioparox effects on nasal mucosa in acute catarrhal rhinosinusitis].

An open, randomized, comparative trial of the drug bioparox was made in 50 patients. Nasal cavity function and its changes in response to bioparox administration were studied with the saccharin test and measurement of ciliary motor activity (CMA) using a special computer program. Significant suppression of the transport function and CMA in all the patients with catarrhal rhinosinusitis was observed. SMA on the inferior turbinated bone and septum was minimal, being low on the middle turbinated bone. After 7 days of bioparox administration mean value of CMA rose 2-fold. Thus, it is demonstrated that bioparox inhalations have no negative effect on nasal ciliated epithelium. On the contrary, it enhances its recovery.

[Visualization of the operative field by adenotome of a new design]. / Vizualizatsiia operatsionnogo polia pri ispol'zovanii adenotoma novoi konstruktsii.

The article describes design characteristics of a new adenotome model for surgery under anesthesia. The results of adenotomy under anesthesia were analysed for 53 patients aged 3 to 14 years made with Beckman's adenotome and the new device. Surgical anatomy of the nasopharynx before the intervention, variants of correlations between adenoid vegetations and other anatomic formations are described. Individual adjustment of the size of the adenotome currete by the distance between Eustachian cushins of the nasopharynx is discussed. The new design of adenotome improves visualization of the operative field during the operation and visual control of the course of surgery.