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OBJECTIVE: The aim of this study is to assess the efficacy and safety of divozilimab in patients who have received post-marketing treatment and participants of clinical trials BCD-132-2 and BCD-132-4 were conducted at the IHB RAS. Additionally, we will present a case report of divozilimab therapy in a patient with highly active multiple sclerosis (MS). MATERIAL AND METHODS: The study included 27 patients with MS. We assessed the dynamics of neurological status, magnetic resonance imaging (MRI) findings, and disability level during divozilimab treatment. We also analyzed the incidence and severity of adverse events (AE), including infusion reactions. RESULTS: During treatment with divozilimab, no exacerbations or radiological disease activity were observed after the first six months. Complete clinical remission was achieved in 25 patients. All 12 patients who received the drug as part of post-marketing use met the NEDA-3 criteria, and five of them showed improvement. Most AE were mild, none exceeding grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE). Laboratory parameter changes were also mild and did not exceed I-II grade according to CTCAE. There were no instances of therapy discontinuation due to intolerance. CONCLUSION: The data from post-registration use of divozilimab confirm the results of clinical trials, showing high efficacy of the drug with a predictable and favorable safety profile.
Subject(s)
Multiple Sclerosis , Humans , Female , Male , Adult , Multiple Sclerosis/drug therapy , Middle Aged , Treatment Outcome , Magnetic Resonance ImagingABSTRACT
The basis for criteria of the taxonomic classification of DNA and RNA viruses based on data of the genomic sequencing are viewed in this review. The genomic sequences of viruses, which have genome represented by double-stranded DNA (orthopoxviruses as example), positive-sense single-stranded RNA (alphaviruses and flaviviruses as example), non-segmented negative-sense single-stranded RNA (filoviruses as example), segmented negative-sense single-stranded RNA (arenaviruses and phleboviruses as example) are analyzed. The levels of genetic variability that determine the assignment of compared viruses to taxa of various orders are established for each group of viruses.
Subject(s)
DNA Viruses , Genome, Viral , RNA Viruses , RNA Viruses/genetics , RNA Viruses/classification , DNA Viruses/genetics , DNA Viruses/classification , Phylogeny , Humans , Animals , Genomics/methods , RNA, Viral/genetics , Genetic VariationABSTRACT
INTRODUCTION: When a new disease occurs, one of the most affordable remedies is drugs containing specific antibodies to this infectious agent. The use of such drugs is aimed at reducing the amount of the pathogen in the macroorganism and the associated reduction in the severity of the symptoms of the disease or recovery. The purpose of this review is to analyze the experience of using immunoglobulins and monoclonal antibodies in the treatment of COVID-19 patients during the pandemic. RESULTS AND CONCLUSION: The two main groups of medical protective agents that block the penetration of the SARS-CoV-2 virus into permissive cells are drugs obtained from blood plasma of convalescents (immunoglobulin) and human monoclonal antibodies. The first group of drugs in the treatment of COVID-19 includes blood plasma of convalescents, which can be successfully used for emergency prevention. The main disadvantage of using blood plasma convalescents is the difficulty of standardization due to the different content of specific antibodies in donors. Another disadvantage is the undesirable side effects in recipients that occur after plasma administration. An alternative approach to COVID-19 therapy is the use of humanized and genetically engineered human monoclonal antibodies against certain epitopes of the SARS-CoV-2 virus. For example, monoclonal antibodies against receptor-binding domain of the S-protein, which prevents the virus from entering permissive cells and interrupts the development of infection. The advantages of these drugs are their safety, high specific activity, and the possibility of standardization. However, the complexity of their production and high cost make them inaccessible for mass use in practical medicine.
Subject(s)
Antibodies, Monoclonal , COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/immunology , SARS-CoV-2/drug effects , COVID-19/immunology , COVID-19/therapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , Immunoglobulins/therapeutic use , Immunoglobulins/immunology , COVID-19 Drug Treatment , COVID-19 Serotherapy , Immunization, Passive , Pandemics , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/immunology , Antiviral Agents/therapeutic useABSTRACT
We analytically examine fluctuations of vorticity excited by an external random force in two-dimensional fluid. We develop the perturbation theory enabling one to calculate nonlinear corrections to correlation functions of the flow fluctuations found in the linear approximation. We calculate the correction to the pair correlation function and the triple correlation function. It enables us to establish the criterion of validity of the perturbation theory for different ratios of viscosity and bottom friction. We find that the corrections to the second moment are anomalously weak in the cases of small bottom friction and small viscosity and relate the weakness to the energy and enstrophy balances. We demonstrate that at small bottom friction the triple correlation function is characterized by universal scaling behavior in some region of lengths. The developed perturbation method was verified and confirmed by direct numerical simulations.
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We present a detailed theoretical analysis of polarized absorption spectra and linear dichroism of cyanine dye aggregates whose unit cells contain two molecules. The studied threadlike ordered system with a molecular exciton delocalized along its axis can be treated as two chains of conventional molecular aggregates, rotated relative to each other at a certain angle around the aggregate axis. Our approach is based on the general formulas for the effective cross section of light absorption by a molecular aggregate and key points of the molecular exciton theory. We have developed a self-consistent theory for describing the orientational effects in the absorption and dichroic spectra of such supramolecular structures with nonplanar unit cell. It is shown that the spectral behavior of such systems exhibits considerable distinctions from that of conventional cyanine dye aggregates. They consist in the strong dependence of the relative intensities of the J- and H-type spectral bands of the aggregate with a nonplanar unit cell on the angles determining the mutual orientations of the transition dipole moments of constituting molecules and the aggregate axis as well as on the polarization direction of incident light. The derived formulas are reduced to the well-known analytical expressions in the particular case of aggregates with one molecule in the unit cell. The calculations performed within the framework of our excitonic theory combined with available vibronic theory allow us to quite reasonably explain the experimental data for the pseudoisocyanine bromide dye aggregate.
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RELEVANCE: Ebola virus disease (EVD) is an acute infectious disease with an extremely high case fatality rate reaching up to 90%. EVD has become widely known since 2014-2016, when outbreak in West Africa occurred and led to epidemic, which caused travel-related cases on the territory of other continents. There are two vaccines against EVD, prequalified by WHO for emergency use, as well as a number of vaccines, approved by local regulators in certain countries. However, even with the availability of effective vaccines, the lack of data on immune correlates of protection and duration of protective immune response in humans and primates is limiting factor for effectively preventing the spread of EVD outbreaks. AIMS: This review highlights experience of use of EVD vaccines during outbreaks in endemic areas, summarizes data on vaccine immunogenicity in clinical trials, and discusses perspectives for further development and use of effective EVD vaccines.
Subject(s)
Ebola Vaccines , Hemorrhagic Fever, Ebola , Animals , Humans , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Travel , Travel-Related Illness , Disease Outbreaks/prevention & controlABSTRACT
Se estudia el componente cardiaco de los reflejos cardiorrenales en 60 ratas adultas, a las que se provoco hipervolemia con dextrosa al 5%, antes y despues del bloqueo de los alfa y beta-adrenorreceptores.La hipervolemia provoco disminucion significativa de la frecuencia cardiaca.El bloqueo de los beta-adrenorreceptores provoco cambios significativos de la frecuencia cardiaca despues de la hipervolemia
Subject(s)
Animals , Rats , Heart Rate , Receptors, Adrenergic, betaABSTRACT
Se estudia el componente cardiaco de los reflejos cardiorrenales en 60 ratas adultas, a las que se provoco hipervolemia con dextrosa al 5%, antes y despues del bloqueo de los alfa y beta-adrenorreceptores.La hipervolemia provoco disminucion significativa de la frecuencia cardiaca.El bloqueo de los beta-adrenorreceptores provoco cambios significativos de la frecuencia cardiaca despues de la hipervolemia
Subject(s)
Animals , Rats , Heart Rate , Receptors, Adrenergic, betaABSTRACT
Se realiza un estudio en un grupo de 30 adolescentes entrenados, 15 de baloncesto y 15 de voleibol, cuya edad promedio fue, respectivamente, de 15,2 más-menos 0,65 y de 15,8 más-menos 1,3, con el objetivo de determinar su eficiencia física y establecer comparaciones con el método directo y otros métodos indirectos. Se utiliza un tiempo de prueba veloergométrica de multietapas discontinuas con cargas submáximas crecientes. El tiempo de ejercicio y de recuperación fue de 6 minutos para cada una de las etapas. Se obtuvo una eficiencia física de 1 000 más-menos 141 kpm/mn para el grupo de baloncesto y de 900 más-menos 154,91 para el grupo de voleibol. Se discuten los métodos indirectos y se establecen conclusiones al respecto(AU)