- allergic inflammation and airway hyper-reactivity in guinea pigs;
- albumin-induced bronchial asthma;
- ovalbumin-induced allergic rhinitis;
- LPS- or formalin-induced rhinitis;
- acute rhinosinusitis;
- experimental tonsillitis;
- LPS-induced acute respiratory distress syndrome;
- chemically induced bronchitis;
- chemically induced pleurisy;
- bronchoalveolitis in rats;
- chemically induced pneumonia;
- pulmonary embolism and chronic productive inflammation of lungs;
- COPD induced by a cigarette smoke;
- pulmonary edema.
The estimated parameters are the follows:
- roentgenograms;
- the weight of lungs (absolute and related to body weight) as a characteristic of pulmonary edema and calculation of pulmonary coefficient. Difference between the weight of dry and wet lung characterizes pulmonary edema;
- bronchopulmonary lavage fluid analysis: cellular structure assessment in lavage fluid (monocytes/macrophages, lymphocytes, eosinophils, neutrophils, basophiles, mast cells) and optionally: analysis of the presence of inflammatory mediators – cytokines (TNF-α, IL-1β, IL-5, IL-13), prostaglandins (PGE2, PGF), leukotrienes, antigen-specific IgE;
- analysis of the presence of inflammatory mediators in blood plasma (IL-1β, TNF-α, IL-8, IL-10);
- assessment of surface-active properties of bronchopulmonary lavage fluid;
- quantitative assessment of plasma extravasation;
- histological examination of bronchus and lung mucous membrane.
Experimental plant for modeling of lung pathology using tobacco smoke (“machine for cigarette smoking”)
The amount of goblet cells in the bronchial mucosa of intact rats and rats being exposed to tobacco smoke
Animals group | Goblet cell count per 1 mm of mucosa |
intact | 32.0±2.2 |
control | 65.0±1.9 |
Bronchus rats. Mucosa with a slight amount of goblet cells (↑), in the submucosal layer of weakly expressed mononuclear infiltration (↑). H & E stain with alcian blue dookraskoy. The increase of 200. | Bronchus rats. Acute catarrhal-purulent bronchitis. Hyperplasia of the mucous and goblet cells (↑), moderately severe and severe and mononuclear leukocyte infiltration of the mucosa and submucosa (↑). H & E stain with alcian blue dookraskoy. The increase of 200. |
Publications by topic:
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- Alexandrova A.E., Shikov A.N., Pozharitskaya O.N., Makarov V.G. Study of anti-inflammatory effect of natural intranasal preparation for treatment of acute rhinitis // Abstr. 50 fh Annual Congress “Society for Medicinal Plant Research”, Barcelona, 8-12 Sept., Barcelona, 2002. – A043. – P. 104.
- Makarova M.N., Tesakova S.V., Guseva S.I., Krishen K.L., Abrashova T. V., Makarov V.G. Efficacy of salvia in experimental model of cervical lymphadenitis in rats // Phytopharm. 2009. 13 th International congress. Book of Leiden. Netherlands. 29-31 July 2009. P.75
- Александрова А.Е., Макаров В.Г., Кузнецов А.С., Вишневецкая Т.П., Дмитриева О.Л., Куренкова Т.Ю., Макарова М.Н. Эликсир Бронхофит – средство для лечения неспецифических воспалительных бронхолегочных заболеваний // Актуальные проблемы создания новых лекарственных препаратов природного происхождения: Матер. IV международного съезда. –СПб. –2000. –С. 123-129.
- Александрова А.Е., Макаров В.Г., Кузнецов А.С., Вишневецкая Т.П., Дмитриева О.Л., Куренкова Т.Ю., Макарова М.Н. Эффективность и механизм действия нового комплексного средства растительного происхождения при неспецифических воспалительных процессах в бронхолегочной системе // Патологическая физиология и экспериментальная терапия. -2003. № 2. –С. 15-17.
- Александрова А.Е., Макарова М.Н. Обоснование к применению экспекторантов растительного происхождения при бронхолегочных заболеваниях // Fito-ремедиум. -2002. -№1/2/. -С. 22-26.
- Александрова А.Е., Соколова Л.И., Пожарицкая О.Н., Шиков А.Н., Макаров В.Г., Зенкевич И.Г. Эликсир “Бронхофит”: главные летучие компоненты и оценка отхаркивающего действия // Фармация. 2001. 1. 18-21.
- Вишневецкая Т.П., Дмитриева О.Л., Жиганова Т.А., Макарова М.Н., Иванова А.В. Изучение противовоспалительных свойств Эликсира Бронхофит // Актуальные проблемы санитарно-эпидемиологического благополучия населения северо-западного региона: Матер. науч.-практ. конференции. -СПб. -2000. -С. 162.
- Гусева С.И., Макарова М.Н., Тесакова С.В., Крышень К.Л., Ацапкина А.А., Буркина П.Н. Разработка экспериментальной модели острого воспаления лимфатического узла у крыс // Материалы научно- практической конференции СПбГМА им. И.И. Мечникова Актуальные проблемы медицины и биологии, Санкт- Петербург.2010 г. С. 371-372.
- Драй Р.В., Макаренко И.Е., Макарова М.Н., Макаров В.Г. Моделирование пневмонии и острого респираторного дистресс-синдрома у крыс с использованием липополисахарида клеточной стенки E.coli // Cб. Трудов первой международной научно-практической конференции «Высокие технологии, фундаментальные и прикладные исследования в физиологии и медицине», Санкт-Петербург, 2010 г С.218-221.
- Тесакова С.В., Самусенко И.А., Карачинская И.В., Крышень К.Л., Абрашова Т.В., Макарова М.Н., Макаров В.Г. Экспериментальная модель шейного лимфаденита у крыс для оценки противовоспалительной эффективности препаратов // Профилактическая и клиническая медицина. – 2011. – №1 (38) С. 57 – 63.
- Рыбакова А.В., Макарова М.Н., Соколов В.Д., Крышень К.Л., Ходько С.В., Макаров В.Г. Методические указания по экспериментальному моделированию ЛПС индуцированной острой пневмонии у крыс. Сообщение № 1 // Международный вестник ветеринарии. – 2013, №4. – С. 106-116.
- Ходько С.В., Макарова М.Н., Макаров В.Г., Михайлова В.С. Изучение специфической фармакологической активности нового препарата «FN» на экспериментальной модели острого риносинусита у крыс // Профилактическая и клиническая медицина. – 2013. – Т. 48, № 3. – С. 58-64.
- Vakchromova E., Kryshen K.L., Seibel J., Makarova M.N., Makarov V.G. Assessment of anti-inflammatiry efficacy of a fixed combination containing thime and IVY extracts in the model of acute bronchoalveolitis in rats //Abstracts. Phitopharm. 2016. Obzory po klinicheskoj farmacologii i lekarstvennoj terapii. -2016. –Vol. 14. –P. 60-61.ASSESSMENT OF ANTI INFLAMMATORY EFFICACY OF A FIXED COMBINATION CONTAINING THYME AND IVY EXTRACTS IN THE MODEL OF ACUTE BRONCHOALVEOLITIS IN RATS
- Katelnikova A.E., Vakhromova E.A., Vorobyova V.V., Shikov A.N. Effects of glycosylated polypeptide complex on IL-1β, TNFα, IL-6 and IL-8 production in the model of acute bronchitis induced by a cigarette smoke // Phitopharm. 2016. Obzory po klinicheskoj farmacologii i lekarstvennoj terapii. – 2016. – Vol. 14. –P. 25.EFFECTS OF GLYCOSYLATED POLYPEPTIDE COMPLEX ON IL-1B PRODUCTION IN THE MODEL OF ACUTE BRONCHITIS INDUCED BY A CIGARETTE SMOKE IN RATS
- Vahromova E.A., Kryshen K.L., Makarova M.N. Evaluation of anti-inflammatory action of the combination of the extracts of thyme and ivy on a model of acute inflammation of lungs in rats // Medical Academic Journal. – 2016. – Vol. 16, number 3. – P. 485-488.
- Katelnikova A.E., Shikov A.N., Makarov V.G., Makarov, M.N. Evaluation of anti-inflammatory properties of complex glycosylated polypeptides on the model of acute bronchitis induced by cigarette smoke in rats // XXVIII Winter Youth Scientific School “Perspective trends of Physico-Chemical Biology and Biotechnology”, Moscow, 08-11 February 2016 pp 173-174.
- Muzhikyan A.A., Khod’ko S.V., Gushchin Ya.A., Makarova M.N., Makarov V.G. Histological changes in the lymph nodes of rats during the modeling of acute cervical lymphadenitis // International bulletin of veterinary Medicine. -2017, No. 1.-C. 75-83.
- Kiseleva I., Krutikova E., Fedorova E., Pisareva M., Krivitskaya V., Kryshen K., Rekstin A., Rudenko L. Cross-protectivity of live attenuated influenza monovalent vaccines against influenza B Yamagata- and Victoria-lineage viruses in ferret model // The sixth ESWI influenza conference. 10-13 September 2017. Riga. –P166.
- Katelnikova A., Kryshen K., Makarova M., Makarov V. Experimental animal models of acute bronchitis. Laboratory Animals for Science. – 2019. – Vol. 1. – P. 1 1-25. https://doi.org/10.29296/2618723X-2019-01-10 SUMMARY. Acute bronchitis (OB) relate to the most pressing problems of modern pulmonology because of the high incidence of people. In this connection, there is a constant search and development of new medicines for the treatment of OB. In order to register new pharmacological substances and preparations based on them, experimental models are needed to evaluate specific pharmacological activity. This review comprehensively discusses the animal species used to model OB, pathology inductors and measured indicators. Search for articles published in English carried out using Google Scholar and PubMed databases (from 1961 to 2018). To search for articles in Russian a database of the scientific electronic library eLIBRARY.RU was used. Fortythree articles were considered acceptable for inclusion in this review. Despite the fact that the review is devoted to modeling OB this included articles with experimental modeling of acute tracheobronchitis, acute bronchopulmonary inflammation, acute lung damage and acute respiratory distress syndrome since the same pathological inducers and routes of administration are often used to model these pathologies. According to peer-reviewed articles mice and rats are mainly used to model acute damage to the lower respiratory tract and lungs. The most popular inducers for modeling acute bronchopulmonary pathology are lipopolysaccharide and cigarette smoke. Mostly used indicators for assessing damage in animals include analysis of bronchoalveolar lavage, histopathology and measurement of edema at different time points after pathology induction. Based on studies aimed to obtain inflammation in the respiratory tract of animals it was confirmed that it is impossible to receive inflammatory damage only in the bronchi, one way or another, lung tissue is involved and vice versa. This information will help researchers choose the appropriate method for the induction of OB in animals and informative indicators for developing a study protocol [Full text is available in Russian].
- Katelnikova A.E., Kryshen K.L., Zueva A.A., Makarova M.N. Intranasal Introduction to Laboratory Animals. Laboratory Animals for Science. –2019, 2. https://doi.org/10.29296/2618723X-2019-02-09 ABSTRACT. The intranasal drug delivery has been become increasingly interesting not only for the treatment of acute and chronic nasal cavity diseases but mainly for drug delivery to the central nervous system and/or systemic blood over the past decades. The high permeability and vascularization of nasal mucosa, coupled with the preventing of the first-pass metabolism and/or drug destruction into gastro-intestinal tract, is provided by intranasal administration. In that regard, such delivery ensures more effective absorption of a tested object than via oral route. The using intranasal delivery of larger molecules not absorbed via oral route (such as peptide-protein drugs and vaccines) has also become a reality even though the nasal absorption of these compounds decreases with their molecular weight. As the demand for drugs with the intranasal administration grows, there is increased need for assessment of pharmacodynamics and toxic properties of drug before pharmaceutical marketing. This article presents an overview of the intranasal administration to laboratory animals. For optimizing the delivery of the agent to the animal and minimizing potential adverse experiences from the procedure it is required a detailed consideration and planning of administration of tested object to laboratory animals. The overview covers the volume of administration, equipment, as well as interspecific nose structure differences, surface area and physiology that need to be taken into account while planning the experiment. To accomplish targeting it may be manipulated variables such as the equipment of administration, volume and pharmaceutical dosage form (liquid, gas, vapor, powder), particle size, chemical properties and composition. The design of research of intranasal administration of tested objects should take into account the volume of administration and the using of anesthesia affecting the delivery performance. These two important factors will determine the relative distribution of the delivered substance to the upper and lower respiratory tracts and entry into the gastrointestinal tract [Full text is available in Russian].
- Matchinin A.A., Katelnikova A.E., Kryshen´K.L. Specific techniques of bronchoalveolar lavage collecting from laboratory animals // Laboratory Animals for Science. – 2019, 4. https://doi.org/10.29296/2618723X-2019-04-06 ABSTRACT. Respiratory organs provide the gas exchange function in which various pathogenic substance and microorganisms causing respiratory diseases can enter the organism and settle in the epithelial surface of lungs and airway tracts. Therefore, diseases of organs respiratory system of various etiologies are most common and affect all mammals. In this regard there is a need to develop drugs for a treatment of respiratory diseases. The bronchoalveolar lavage is the traditional invasive technique allowing to collect lavage from animals’ airway tracts and lungs for diagnosis of diseases in veterinary or for researching respiratory toxicity of test medicines in preclinical studies. The technique of bronchoalveolar lavage is frequently used because this procedure represents a simple and cost-effective method and makes it possible to minimize physical damaging of animal for subsequent postoperative recovery, if necessary. The advantage of bronchoalveolar lavage fluid analysis is that one can pick up early indicators of biochemical, cytology and microbiology changes leading to later morphological changes in a disease process. It is important to correctly perform the procedure of sampling, processing and analyzing of bronchoalveolar lavage fluid, i.e.: any damage to the lungs and respiratory tracts must be avoided; to carry out manipulations with samples of flushing of the respiratory system as soon as possible and in a cooled state. This procedure is based on washing of lungs and respiratory tracts with a isotonic wash fluid, but it has sequence of specificities that depend on the animal species and the purpose of collecting bronchoalvolar lavage: the choice of an open or closed method, wash fluid, its volume and number of wash fluid recovery and other specificities. In current review various specific techniques of bronchoalveolar lavage collecting have been considered, which should be taken into account when achieving the task, as well as what components included in the bronchoalveolar lavage can be studied [Full text is available in Russian].
- Kiseleva I., Stepanova E., Krutikova E., Donina S., Rekstin A., Bazhenova E., Pisareva M., Katelnikova A., Kryshen K., Muzhikyan A., Grigorieva E., Rudenko L. Could trivalent LAIV protect against both genetic lineages of influenza B virus? // VaccineResearch. – 2020. – Vol. 11. – P. 13-24. DOI: 10.29252/vacres.6.1.13.
- Kargopoltceva D.R., Katelnikova A.E., Kryshen K.L., Guschin Ya.A. Features of the respiratory system of animals used in pre-clinical studies which should be taken account of the modeling lung pathologies. Laboratory Animals for Science. – 2020, №4. https://doi.org/10.29296/2618723X-2020-04-08 Abstract. The respiratory system is one of the most important systems of organism, providing oxygen from the air to respiratory tract, carrying out gas exchange and removing carbon dioxide back into the environment. Respiratory system diseases affect at the lives of large numbers of people around the world. Planning studies with assessment of pharmacological activity and toxicity of drugs via endotracheal and inhalation routes of administration it should be considered specific features in anatomy, microstructure and pathophysiological processes in various animal species, including in comparison with humans. This review considers anatomical and histological features of respiratory system of mice, rats, guinea pigs, rabbits, pigs and dogs, which are used in biomedical studies and their comparative characteristics regard to the structure of respiratory system in humans. Studying of literature data, it was found that the most similarity to humans, both at macroscopic and microscopic levels, is in guinea pigs and dwarf pigs. The search for articles published in English was carried in the Google Scholar and PubMed (1970–2020) databases, in Russian – in the scientific electronic library eLIBRARY.RU. In addition to considering anatomical and histological features of respiratory system structure of laboratory animals, this review also included models of lung pathologies reproduced in the animals listed above. So, to modeling chronic obstructive pulmonary disease, fibrosis, inflammation, emphysema mice and rats are used. Mice of certain lines like guinea pigs are used to modeling asthma. Laboratory animals are also used to reproduce bacterial and viral diseases of respiratory system. Thus, a very careful approach to selection of a test system is required for modeling diseases of respiratory system. This is necessary to obtain more similar clinical symptoms and pathophysiological processes with humans in certain lung pathologies, which in the future will make it possible to better predict pharmacodynamic and toxic effects of drugs in clinical practice [Full text is available in Russian].