Effect of triazavirine on the outcome of a lethal influenza infection and secondary bacterial pneumonia following influenza in mice

Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log10TCID50/ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans.Pneumonia often occurs as secondary infection post influenza disease and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. The antiviral drug triazavirine is licensed in Russia for the treatment and prophylaxis of acute respiratory infections, including influenza A and B viruses. In the present study, we investigated the efficacy of triazavirine in a mouse model of secondary Staphylococcus aureus pneumonia following A/California/04/2009 (H1N1)pdm09 influenza virus infection. We also performed a study of the efficacy of triazavirine against the A/California/04/2009 (H1N1)pdm09 lethal influenza infection in mice. In this model, triazavirine at the dose of 25 mg/kg/day significantly enhanced the survival of animals (60% compared to 20%) and the mean survival time to death, prevented weight loss, and reduced viral titer in the lungs of mice infected with influenza virus. At doses of 50 and 100 mg/kg/day, triazavirine was highly effective in the treatment of the secondary bacterial pneumonia following influenza infection in mice. At these doses, triazavirine protected 67-75% of animals against death, increased the mean survival time to death by twofold, and reduced the virus titer by 2.2-3.0 log10TCID50/ml compared to the mice in the control group. These findings suggest the possible benefit of triazavirine treatment in reducing post influenza pneumonia incidence in humans

Changes in University Teacher’s Pedagogical Activity in the Context of Digitalization of Education

The purpose of this article is to consider the changes in university teacher’s pedagogical activity in the conditions of a rapid transformation of higher education and propose a theoretical and empirical substantiation of the importance of teacher’s understanding of the value-semantic attitude to pedagogical activity, which is not limited only to mastering digital competencies, but consists in mastering pedagogical knowledge that allows you to critically analyze the productivity of modern educational strategies and methods.The conducted research was based on the methodology of post-non-classical science, which implies the widespread use of qualitative research methods that reflect the convergence of explanatory and interpretative research approaches, the use of representations, opinions, attitudes, and values of the research participants as full data.The article describes the results of studying the university teachers’ attitude to changes, the value orientations of the ongoing changes, as well as the main difficulties faced by university teachers in the context of digitalization of education – the design of educational and training programs, modern educational and methodological complex, the organization of productive self-directed work and communication with students in the educational process.The main directions of overcoming the identified difficulties are given – the construction of flexible curricula within the framework of the Federal State Educational Standard of Higher Education, the development of the digital educational environment of the university and updating the content of the professional development programs for teaching staff. The conclusion is made about the increasing importance of pedagogical knowledge in teacher’s professional activity in the conditions of a modern university

Influenza virus infection and postviral bacterial pneumonia pathogenesis induced by different subtypes of influenza virus in mice

Secondary bacterial infections after influenza virus infection further increase morbidity and mortality due to influenza. Despite of seasonal influenza vaccination, antiviral drugs and antibiotics are widely used in viral/bacterial pneumonia therapy. Therefore, further comprehensive study of the infection pathogenesis is relevant. Murine models for influenza virus infection were reproduced with different virus subtypes A/California/04/2009MA (pandemic H1N1 2009), A/Puerto Rico/8/34 (H1N1) and A/Aichi/2/69 (H3N2), Anadyr/177/2009 (H1N1) and for post-influenza bacterial pneumonia caused by the Gram-positive Staphylococcus aureus. After the infection occurs, its pathogenic features were detected by daily monitoring the mortality (survival) and morbidity rate (body weight loss) and, in addition, viral pathogenesis also was evaluated by assessing virus replication (viral titer) and humoral immune responses (production of pro- and anti-inflammatory cytokines) in respiratory tract of infected mice including during antiviral (oseltamivir) and antibacterial (cefuroxime) therapy. Mortality and virus titer in the infected mice did not differ significantly between the groups of different influenza A virus subtypes. However, production of cytokines (IL-10, IFNg, TNFa) and weight gain proved to be different. Mortality of the mice reached 100% after secondary bacterial infection, whereas IFNg and TNFa levels in mice lung increased reached maximal values in the treated groups. Viral subtype A/California/04/2009MA of influenza A was most pathogenic in mouse model of secondary bacterial pneumonia. Antiviral and antibacterial treatment caused a decrease in mortality, reduced viral titers in lungs, and retain body weight gain of mice. According to these points, the treatment groups did not significantly differ from each other. At the same time, it should be noted that the cytokine production significantly decreased in the treated groups, and IL-10 and IFNg levels in lungs were different, that may be due to therapeutic mechanisms of these drugs. Thus, antiviral therapy for influenza infection and combination therapy for viralbacterial pneumonia can be an effective tool to reduce mortality of influenza

Цитотоксичные катионные пептиды как лиганды рецепторного нуклеолина

Background. Chaperone proteins nucleolin (NCL, or C23) and nucleophosmin (NPM, or B23) regulate key cell functions. The most tumors are characterized by over-expression of these proteins, especially in cell nuclei and on the сell surface, as NCL. Differential expression of NCL/NPM in tumor and normal cells is the basis of selective cytotoxicity of cationic peptides – expected ligands for these proteins. Objective. Analysis of the interactions between nucleolin and some peptides with high nonspecific toxicity for tumor cells. Materials and methods. The interaction of 4 previously characterized cationic peptides with nucleolin dimer was analyzed by pair molecular docking using Maestro 11 program. Results and conclusion. It is shown that these peptides can associate with receptor nucleolin molecules, forming energy-stable complexes. In the active centre of NCL molecule were found, at least, 7 positions of amino acids, which bind to the tested peptides at a high frequency (43–100 %). This indicates the conservative structure of dimer NCL, its stable binding to peptide ligands and the possibility of design the optimal structure of cationic peptides that induce tumor cell death due to competing binding to the target proteins.Введение. Шаперонные белки нуклеолин (NCL, или С23) и нуклеофозмин (NPM, или В23) регулируют ключевые клеточные функции. Для большинства опухолей характерна гиперэкспрессия этих белков, особенно в клеточных ядрах, а рецепторного NCL – также и на поверхности опухолевых клеток. Дифференциальная экспрессия NCL/NPM в опухолевых и нормальных клетках обусловливает избирательную цитотоксичность катионных пептидов – предполагаемых лигандов этих белков. Цель исследования – анализ взаимодействий между нуклеолином и некоторыми пептидами, обладающими высокой избирательной токсичностью в отношении опухолевых клеток. Материалы и методы. Путем парного молекулярного докинга с использованием программы Maestro 11 проанализировано взаимодействие 4 ранее охарактеризованных катионных пептидов с димером нуклеолина. Результаты и заключение. Показано, что эти пептиды могут ассоциировать с молекулами рецепторного нуклеолина за счет стабильных водородных связей, образуя энергетически устойчивые комплексы. В активном центре рецепторного NCL обнаружено не менее 7 аминокислотных сайтов, которые с высокой частотой (43–100 %) связываются с тестированными пептидами. Это указывает на консервативность структуры димерного NCL, стабильное связывание его с пептидными лигандами и возможность синтеза оптимальных по молекулярной структуре катионных пептидов, индуцирующих гибель опухолевых клеток за счет конкурирующего связывания с белками-мишенями.

Cytotoxic cationic peptides as а ligands for receptor nucleolin

Background. Chaperone proteins nucleolin (NCL, or C23) and nucleophosmin (NPM, or B23) regulate key cell functions. The most tumors are characterized by over-expression of these proteins, especially in cell nuclei and on the сell surface, as NCL. Differential expression of NCL/NPM in tumor and normal cells is the basis of selective cytotoxicity of cationic peptides – expected ligands for these proteins. Objective. Analysis of the interactions between nucleolin and some peptides with high nonspecific toxicity for tumor cells. Materials and methods. The interaction of 4 previously characterized cationic peptides with nucleolin dimer was analyzed by pair molecular docking using Maestro 11 program. Results and conclusion. It is shown that these peptides can associate with receptor nucleolin molecules, forming energy-stable complexes. In the active centre of NCL molecule were found, at least, 7 positions of amino acids, which bind to the tested peptides at a high frequency (43–100 %). This indicates the conservative structure of dimer NCL, its stable binding to peptide ligands and the possibility of design the optimal structure of cationic peptides that induce tumor cell death due to competing binding to the target proteins

INDUCTION OF SECONDARY BACTERIAL PNEUMONIA IN MICE INFECTED WITH PANDEMIC AND LABORATORY STRAINS OF THE H1N1 INFLUENZA VIRUS

Aim. In this study we developed and characterized a mouse model of secondary S. aureus and S. pneumoniae pneumonia following influenza virus infection with H1N1 pandemic and laboratory strains and their reassortment. Materials and methods. BALB/с mice were infected intranasally with A/California/04/2009/(H1N1 pndm), A/Puerto Rico/8/34 or their reassortment NIBRG-121xp followed by different strains of S. аureus и S. pneumoniae. The pathogenicity of infection was assessed by mouse survival and weight change, viral titre and bacterial count in the lungs. Results. It was shown that the infection of mice with three strains of the H1N1 influenza virus with a comparable level of pathogenicity leads to a different severity of secondary bacterial infection. The mouse adapted A/California/04/2009 pandemic strain possessed the greatest ability to alter antibacterial immunity. Conclusion. An experimental model of post-influenza bacterial pneumonia utilizing three strains of the H1N1 influenza virus and various strains of S. aureus or S. pneumoniae was established. The ability of viruses to provoke bacterial superinfection of different severity is characterized

From the Sun to the Earth: The 13 May 2005 Coronal Mass Ejection

We report the results of a multi-instrument, multi-technique, coordinated study of the solar eruptive event of 13 May 2005. We discuss the resultant Earth-directed (halo) coronal mass ejection (CME), and the effects on the terrestrial space environment and upper Earth atmosphere. The interplanetary CME (ICME) impacted the Earth's magnetosphere and caused the most-intense geomagnetic storm of 2005 with a Disturbed Storm Time (Dst) index reaching -263 nT at its peak. The terrestrial environment responded to the storm on a global scale. We have combined observations and measurements from coronal and interplanetary remote-sensing instruments, interplanetary and near-Earth in-situ measurements, remote-sensing observations and in-situ measurements of the terrestrial magnetosphere and ionosphere, along with coronal and heliospheric modelling. These analyses are used to trace the origin, development, propagation, terrestrial impact, and subsequent consequences of this event to obtain the most comprehensive view of a geo-effective solar eruption to date. This particular event is also part of a NASA-sponsored Living With a Star (LWS) study and an on-going US NSF-sponsored Solar, Heliospheric, and INterplanetary Environment (SHINE) community investigation. © 2010 The Author(s)