[Efficacy and safety of bacterial lysate OM-85 in the treatment of uncomplicated acute respiratory infections: a double-blind, placebo-controlled, multicenter, randomized trial].

AIM: To evaluate the efficacy and safety of OM-85 in the treatment of uncomplicated acute respiratory infections (ARI) in adults. MATERIALS AND METHODS: A double-blind, placebo-controlled, multicenter, randomized trial included 556 patients (18-60 years old) with mild and moderate ARI and negative results of polymerase chain reaction analysis for SARS-CoV-2 RNA and rapid test for influenza A and B viruses. Patients were randomized into two groups: in the first group (n=278), patients received OM-85 (Broncho-munal®) one capsule 7 mg/day for 10 days, while the second group (n=278) was treated with placebo in the same regimen. The primary endpoint was the dynamics of the severity of symptoms over 3, 5, 7 and 10 days of treatment according to the 21-item Wisconsin Upper Respiratory Symptom Survey (WURSS-21), which was assessed by the area under the curve. Secondary efficacy criteria were the dynamics of the severity of symptoms according to the Common Cold Questionnaire (CCQ), the time to the resolution of symptoms according to WURSS-21 and CCQ, the proportion of patients with body temperature below 37°C on each day of treatment, frequency of the need for systemic antibacterial therapy. RESULTS: The superiority of OM-85 over placebo by primary endpoint was observed on the 5th, 7th and 10th days of treatment. OM-85 efficacy has also been proven by secondary criteria. OM-85 shortened the time until the symptoms of ARI resolved according to the WURSS-21 and CCQ, increased the proportion of patients with body temperature below 37°C by 2-9 days. The time needed to resolve the symptoms of disease in 20% of patients according to WURSS-21 was 7 and 9 days in patients taking OM-85 and placebo, respectively. Bacterial lysate increased the probability of complete disappearance of symptoms according to CCQ by 45.7% compared to placebo. The analysis of the frequency and severity of adverse events, laboratory tests, physical and instrumental examination results during treatment confirmed the good tolerability and safety of OM-85. CONCLUSION: The study confirmed the efficacy and safety of OM-85 in the complex treatment of ARI in adults.

[New opportunities for preventive anti-inflammatory therapy in the management of patients with moderate and severe COVID-19].

The specific feature of new coronavirus infection (COVID-19) is high risk of hyperinflammatory response or cytokine storm development, which underly the pathogenesis of several life-threatening conditions and determine the disease outcomes. Pathophysiological features of COVID-19 justify the search of effective drugs capable to control the hyperinflammatory response. AIM: To evaluate the efficacy and safety of Aterixen (1-[2-(1-Мethylimidazol-4-yl)-ethyl]perhydroazin-2,6-dion) for achieving clinical improvement in adult patients hospitalized with moderate and severe COVID-19. MATERIALS AND METHODS: Multicenter, adaptive, randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of Aterixen , tablets, 100 mg, in patients with COVID-19. The study analysis included 116 patients who, by randomization, were divided into 2 groups: 57 patients were included in the Aterixen drug group and 59 patients were in the placebo group. RESULTS AND CONCLUSION: Obtained results have shown high efficacy and statistically significant superiority of Aterixen over placebo. Thus, it allows us to consider it as viable medication for COVID-19 pathogenetic therapy.

[Risks of oncologic pathology in parasitosis at the present time].

An analysis of published literature data on the relationship of parasitic diseases and oncogenesis is carried out. Current knowledge about the association of parasitic infections and cancer formation has revealed several carcinogenic mechanisms, but the severity of the relationship between parasites and cancer formation (except for schistosome, opisthorchis and clonorchis) should be confirmed in future experimental and population studies.

[The Russian consensus on the diagnosis and treatment of chronic pancreatitis: Enzyme replacement therapy]. / Rossiiskii konsensus po diagnostike i lecheniiu khronicheskogo pankreatita: zamestitel'naia fermentnaia terapiia.

Pancreatology Club Professional Medical Community, 1A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow; 2A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow; 3Kazan State Medical University, Ministry of Health of Russia, Kazan; 4Kazan (Volga) Federal University, Kazan; 5Far Eastern State Medical University, Ministry of Health of Russia, Khabarovsk; 6Morozov City Children's Clinical Hospital, Moscow Healthcare Department, Moscow; 7I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint Petersburg; 8Siberian State Medical University, Ministry of Health of Russia, Tomsk; 9M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow; 10Maimonides State Classical Academy, Moscow; 11V.I. Razumovsky State Medical University, Ministry of Health of Russia, Saratov; 12I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow; 13S.M. Kirov Military Medical Academy, Ministry of Defense of Russia, Saint Petersburg; 14Surgut State Medical University, Ministry of Health of Russia, Surgut; 15City Clinical Hospital Five, Moscow Healthcare Department, Moscow; 16Nizhny Novgorod Medical Academy, Ministry of Health of Russia, Nizhny Novgorod; 17Territorial Clinical Hospital Two, Ministry of Health of the Krasnodar Territory, Krasnodar; 18Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg; 19Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don; 20Omsk Medical University, Ministry of Health of Russia, Omsk; 21Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia, Moscow; 22Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk; 23Stavropol State Medical University, Ministry of Health of Russia, Stavropol; 24Kemerovo State Medical University, Ministry of Health of Russia, Kemerovo; 25N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow; 26A.M. Nikiforov All-Russian Center of Emergency and Radiation Medicine, Russian Ministry for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters, Saint Petersburg; 27Research Institute for Medical Problems of the North, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk; 28S.P. Botkin City Clinical Hospital, Moscow Healthcare Department, Moscow; 29Tver State Medical University, Ministry of Health of Russia, Tver The Russian consensus on the diagnosis and treatment of chronic pancreatitis has been prepared on the initiative of the Russian Pancreatology Club to clarify and consolidate the opinions of Russian specialists (gastroenterologists, surgeons, and pediatricians) on the most significant problems of diagnosis and treatment of chronic pancreatitis. This article continues a series of publications explaining the most significant interdisciplinary consensus statements and deals with enzyme replacement therapy.

[STEPPED DIET THERAPY OF ACUTE ENTERIC INFECTIONS IN CHILDREN].

The article describes the main principles of stepped diet therapy of acute intestinal infections in children developed on the basis of nutritive support staging, depending on patients' age, stage and severity of disease. Significance of functional food products for diet therapy tactics in patients with mild and moderately severe forms of infection is demonstrated.

[ADENOVIRUSES IN THE ETIOLOGICAL STRUCTURE OF ACUTE RESPIRATORY VIRAL INFECTION IN MOSCOW IN 2004 - 2014].

AIM: Study prevalence of adenovirus species and serotypes that had caused acute respiratory viral infection (ARVI) in Moscow in 2004 - 2014. MATERIALS AND METHODS: Material from respiratory tract of 4731 patients with ARVI and 663 conditionally healthy children and adults was used. ARVI causative agents were detected by PCR with real-time detection using AmpliSens reagent kits (CRIE, Moscow). Membership of adenoviruses to a certain serotype was determined by sequencing of hexon gene segment. Adenoviruses that had caused ARD in servicemen in 2010 - 2014 were also studied. RESULTS: ARVI causative agents were detected in 64.6% ill children and 58% of adults. Respiratory-syncytial and rhinoviruses prevailed in children, influenza A virus--in adults. Adenoviruses were detected in 6.9% of ill children and 2.9% of adults during the whole year, with a rise in October-December. B and C species occurred at an equal frequency, E species was found less often. Serotypes 3 and 2 prevailed in 34% and 21% of cases of adenovirus mono-infection, respectively, serotypes 7, 6 and 4 occurred less often. 4 out of 5 outbreaks of adenovirus infection in servicemen were caused by serotype 7. Adenoviruses were absent in the group of healthy adults, in conditionally healthy children were detected in 0.4% of cases and were attributed to serotypes 1 and 2. CONCLUSION: Etiological structure of ARVI was studied for the last decade. Adenovirus infection ranked 5th in children and 7th in adults. 9 serotypes of 3 species of respiratory adenoviruses were identified. Varying prevalence of species and serotypes depending in season, clinical diagnosis and patient age was demonstrated.

[Laboratory diagnostics in evaluation of acute respiratory viral infection morbidity in 2010 - 2011 epidemic season].

AIM: Study of etiological structure of ARVI and evaluation of acute respiratory virus infection morbidity in 2010 - 2011 epidemic season taking into account the data of laboratory diagnostics by method of polymerase chain reaction with hybridization-fluorescent detection. MATERIALS AND METHODS: By using reagent kits produced by Central Research Institute of Epidemiology for the detection of primary causative agents of influenza and ARVI 129 children and 94 adult patients monitored in an outpatient setting as well as 103 children hospitalized due to ARI were examined. RESULTS: Etiological structure of ARVI was studied; proportion of influenza and other actual causative agents of ARVI in monthly dynamics were established. During epidemic rise of influenza (January-March 2011) the proportion of influenza A viruses was 24% (peak in January--31%), the proportion of influenza B viruses--5%, rhinoviruses--9%, metapneumovirus was detected in 6% of cases, parainfluenza viruses (1 - 4 type) and adenovirses--4% each, coronaviruses--in 3%, respiratory syncytial virus--in 2%, bocavirus--in 1% of the studied samples. In influenza structure A/H1N1pdm2009 virus, its proportion was 70%, influenza virus B (26.9%), influenza virus A/H3N2 (2.6%) predominated. Indexes for monthly morbidity caused by each of the ARVI causative agents were calculated. CONCLUSION: The proposed approach allowed to evaluate ARVI morbidity taking into account laboratory-confirmed etiological factors. A 5 time increase in ARI morbidity in adults in February 2011 was shown to be mostly due to an increase in influenza A morbidity as well as involvement of influenza B virus, metapneumoviruses, coronaviruses, parainfluenza viruses and rhinoviruses into the epidemic process. Increase of morbidity of children by 1.4 times was also seen during activization of influenza viruses and metapneumovirus. The analysis of monitoring results allowed to prognose increase of respiratory-syncytial viral infection epidemic activity from September 2011 to February 2012.

[Use of new synbiotics in treatment of the intestinal infections among children].

The article deals with the findings of the complex estimate of the new synbiotic product "Life Harmony" to treat acute intestinal infection among children. The authors show that application of this product, containing B. bifidum, B. longum and L. casei strains, in the diet therapy of the acute intestinal infections of "the watery" type among children contributes to the reduction of the duration of anorexia, flabbiness and diarrhea syndrome, as well as provides a complete recovery of the intestinal microflora balance.

[Helicobacter pylori-associated pathology of oral cavity in children (clinical-laboratory study)].

As the result of the study of stomatological status indices in children with gastroduodenal pathology associated with Helicobacter pylori it was established that caries incidence in children did not depend upon contamination while caries prevalence in examined children unlike caries incidence was associated with HP-status of the oral cavity. Patients with concomitant gastroduodenal pathology had frequently periodontal disease (PD). In children with chronic antral gastritis associated with Helicobacter pylori clinical manifestations were poor and tended towards inflammatory process chronicity. All the patients had chronic catarrhal gingivitis. In children with Helicobacter pylori associated pathology of GIT it proceeded with 100% contamination of gingival mucous membrane by Helicobacter pylori as shown by bacterioscopic study.

Use of thermosensitive polymer material on the basis of N-isopropylacrylamide and N-tert-butylacrylamide copolymer in cell technologies.

We developed thermosensitive polymer substrates on the basis of N-isopropylacrylamide and N-tert-butylacrylamide co-polymer and studied their interaction with cultured substrate-dependent mammalian cells. It was shown that these polymers promote cell adhesion and proliferation at a level comparable to polystyrene treated for cell culturing and provide effective cell detachment after lowering culturing temperature below a critical level determined by phase transition temperature in aqueous solutions of polymers. A dependence of phase transition temperature on the ratio between N-isopropylacrylamide and N-tert-butylacrylamide was demonstrated. Differences in the dynamics of cell detachment from the surface of polymer substrates with various proportions between the components were shown.

[Detection of sapoviruses in children with acute gastroenteritis in Moscow in 2002-2003].

Sapoviruses were found, for the first time, to be circulating in children with acute gastroenteritis in the city of Moscow. On the basis of a genetic analysis, they were classified as belonging to genotypes 1 and 2. Two groups of sapoviruses that are essentially different from the strains presented now at the GenBank NCBI were described within the case study.

Poly(N-isopropylacrylamide) copolymer films as vehicles for the sustained delivery of proteins to vascular endothelial cells.

The aim of this study was to establish the capacity of thermoresponsive poly(N-isopropylacrylamide) copolymer films to deliver bioactive concentrations of vascular endothelial growth factor (VEGF165) to human aortic endothelial cells (HAEC) over an extended time period. Films were prepared using a 50:50 (w/w) mixture of non-crosslinkable and crosslinkable copolymers of the following monomer compositions (w/w): 85:15, N-isopropylacrylamide (NiPAAm):N-tert-butylacrylamide (NtBAAm); and 85:13:2 NiPAAm:NtBAAm:acrylamidobenzophenone (ABzPh, crosslinking agent), respectively. After crosslinking by UV irradiation, the ability of films to incorporate a fluorescently labeled carrier protein (FITC-labeled BSA, 1 mg loaded per film), at 4 degrees C, was first established. Incorporation into the matrix was confirmed by the observation that increasing film thickness from 5 to 10 microm increased release from collapsed films at 37 degrees C (1.76 +/- 0.15 and 10.98 +/- 3.38 microg/mL, respectively, at 24 h postloading) and that this difference was maintained at 5 days postloading (1.81 +/- 0.25 and 13.8 +/- 2.3 microg/mL, respectively). Incorporation was also confirmed by visualization using confocal microscopy. When 10-microm films were loaded with a BSA solution (1 mg/mL) containing VEGF165 (3 microg/mL), sustained release of VEGF165 was observed (10.75 +/- 3.11 ng at 24 h; a total of 31.32 +/- 8.50 ng over 7 days). Furthermore, eluted VEGF165 increased HAEC proliferation by 18.2% over control. The absence of cytotoxic species in medium released from the copolymer films was confirmed by the lack of effect of medium (incubated with copolymer films for 3 days) on HAEC viability. In conclusion this study has shown that NiPAAm:NtBAAm copolymers can be loaded with a therapeutic protein and can deliver bioactive concentrations to human vascular endothelial cells over an extended time period.

Extended delivery of the antimitotic agent colchicine from thermoresponsive N-isopropylacrylamide-based copolymer films to human vascular smooth muscle cells.

The aim of this study was to establish the capacity of thermoresponsive poly(N-isopropylacrylamide) copolymer films to deliver bioactive concentrations of an antimitotic agent to human vascular smooth muscle cells (HASMC) over an extended period of time. Copolymer films were prepared using a 50:50 (w/w) ratio of N-isopropylacrylamide (NiPAAm) monomer to the more hydrophobic N-tert-butylacrylamide (NtBAAm) and loaded with the antimitotic agent colchicine (0.1 micromol per film) at room temperature. Colchicine release from films was sustained over a 14-day period. At 24 h postloading, the concentration of colchicine in the medium overlying films was 2.12 +/- 0.16 microM; this fell to 0.20 +/- 0.01 microM at 7 days and decreased further to 0.12 +/- 0.01 microM after 14 days. Colchicine released from copolymer films inhibited proliferation when subsequently placed on HASMC: at 0.1 microM, released colchicine reduced proliferation to 18.5 +/- 0.8% of control cells (p < 0.001, n = 9). The antiproliferative effect of released colchicine was comparable to that of native colchicine, as observed in separate experiments. Furthermore, colchicine released from 50:50 polymer films inhibited the proliferation of cells grown in the same environment as the copolymer. Inhibition of cell proliferation was not due to the release of cytotoxic particles from the copolymer because medium incubated with copolymer for 5 days and then applied to HASMC did not alter cell viability. In conclusion, this study demonstrates that 50:50 NiPAAm:NtBAAm copolymers can deliver bioactive concentrations of the antimitotic agent colchicine to human vascular cells over an extended period of time.

[Etiological structure of acute respiratory viral infections in children hospitalized in 1981-1999]. / Etiologicheskaia struktura ORVI u detei, gospitalizirovannykh v statsionar za 1981-1999 gg.

The role of influenza and parainfluenza viruses, respiratory syncytial viruses and adenoviruses in the etiological structure of morbidity in acute respiratory virus infections (ARVI) in children hospitalized during the 19 year period is analyzed. As the result of examination of 56,287 patients by direct immunofluorescent test, respiratory viruses were detected in 21% of cases. The seasonal character, periodicity and level of ARVI morbidity were established. According to medical records, in the 1990s ARVI took a more severe course in children than that observed in the 1980s. In addition, the data on morbidity among children regarding rotavirus infection and ARVI were found to be similar.

A simple and effective separation and purification procedure for DNA fragments using dodecyltrimethylammonium bromide.

In this work we describe a simple two step separation procedure for the separation and purification of short DNA fragments. The first step involves precipitating the DNA using the cationic surfactant dodecyltrimethylammonium bromide. Dodecyltrimethylammonium bromide, unlike cetyltrimethylammonium bromide will not precipitate DNA before complexation is complete thus providing a high purity DNA. The second step involves dissolution of the DNA-dodecyltrimethylammonium complex in 75% ethanol, followed by precipitation of the Sodium-DNA salt, by titrating in a salt solution. This method is particularly suited to purification of short fragments as it does not require high salt concentrations in the ethanol precipitation step, which can be damaging for short DNA. The ability of dodecyltrimethylammonium bromide to remove ethidium bromide from intercalation sites on the DNA is also discussed

[Effect of thermoreverse polymer matrix and collagen on the growth of human fibroblasts]. / Vliianie matriksa na osnove termoreversivnykh polimerov i kollagena na rost fibroblastov cheloveka.

The effect of a support composed of polymers based on poly-N-isopropyl acrylamide and poly-t-butyl acrylamide and collagen on human fibroblasts was studied. As the temperature was decreased to 4 degrees C, the polymeric support is converted to a diluted state and cells spontaneously detached from it. The presence of collagen in the support prevented the detachment of cells and increased cell growth. It was shown by microcalorimetry, that in a copolymer-collagen mixture, a microstratification takes place.

Stoichiometry of dipalmitoylphosphatidylcholine-DNA interaction in the presence of Ca2+: a temperature-scanning ultrasonic study.

DNA-DPPC complexes can be prepared by means of a single step procedure of mixing DNA solution and aqueous lipid dispersion in the presence of calcium ions. Interaction between DPPC and DNA brings about a biphasic shape of melting curves corresponding to the free lipid and the strongly bound one. The amount of the strongly bound lipid is 5 molecules per nucleotide which is close to the size of the first lipid monolayer around DNA molecule.

Capillary electrophoretic study of the complex formation between DNA and cationic surfactants.

Due to the growing interest in the use of cationic surfactants for the construction of liposomal genetic delivery systems, the study of complex formation between DNA and quaternary ammonium detergents is of fundamental importance. In this context, we undertook the study of this complex formation using capillary zone electrophoresis (CZE) with suppressed electroosmotic flow, a technique that allowed us to both monitor the change in mobility of DNA as a function of added surfactant in a precise and reproducible manner and evaluate the potential of CZE to reflect the change in hydrodynamic friction upon binding. Nevertheless, CZE must be applied with caution for binding studies where strong cooperativity occurs, because of the presence of peak splitting at concentrations close to the half-point of binding. Also, a comparison between this experiment and Manning's polyelectrolyte transport properties theory on one hand and Tirado and Garcia de la Torre expression for hydrodynamic friction of rod-like molecules on the other hand is given.