- Details
- Hits: 635
SSN 2410-7751 (Print)
ISSN 2410-776X (Online)
iotechnologia Acta Т. 15, No. 1, 2022
P. 72-80. Bibliography 22, Engl.
UDC: 579.6:604
https://doi.org/10.15407/biotech15.01.072
T. S. Todosiichuk 1, O. V. Pokas 2, S. О. Soloviov 3, T. S. Ryzhkova 1
1Igor Sikorsky Kyiv Polytechnic Institute, Kyiv
2SI “L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of NAMS of Ukraine”, Kyiv
3 Shupyk National Healthcare University of Ukraine, Kyiv
Aim. Evaluation of biotechnological aspects of the production of a liquid formulation of the multifunctional antiseptic preparation of microbial origin, which can be typified as an enzybiotic; characterization of the enzyme specificity of the studied formulation, stabilization methods, its ability to affect microbial biofilms.
Methods. Gel-filtration and electrophoresis were used to study the component composition and the specificity of the enzyme complex of the Streptomyces albus UN 44 producer strain. Proteolytic and staphylolytic activities of individual fractions were determined. The Pseudomonas aeruginosa biofilm and its formation under the effect of various drug formulations were quantitatively evaluated by spectrophotometry.
Results. The stability of the liquid formulation of the enzybiotic biosynthesized by S. albus UN 44 was demonstrated. Activity of the formulation could be prolonged and additionally stabilized by adding of 0.5% polyvinyl alcohol. Fractionation of the formulation enzyme complex using gel-filtration revealed the presence of at least three proteinases of different molecular weights (80-100, 24-35 and 20 kDa) and lysoenzymes (18-22 kDa). The effectiveness of the developed liquid antibiotic formulation for the destruction and inhibition (8-10 folds) of the biofilm formation by clinical strains of P. aeruginosa was shown.
Conclusions. The broad spectrum, multidirectional mechanisms of antimicrobial and regenerative action of enzybiotic drug, and the possibility of its production directly from the biotechnological process determine the prospects of its manufacturing and use as a multifunctional surface antiseptic.
Key words: antibiotic, antimicrobial action, Streptomyces albus, liquid formulation, biofilms, pathogens.
© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2022
References
1. P?rv?nescu H., B?l??oiu M., Ciurea M. E., B?l??oiu A. T., M?nescu R. Wound infections with multi-drug resistant bacteria. Chirurgia (Bucur). 2014, 109 (1), 73–79. https://www.revistachirurgia.ro/pdfs/2014-1-73.pdf
2. Valencia I. C., Kirsner R. S., Kerdel F. A. Microbiologic evaluation of skin wounds: alarmingtrendtowardantibioticresistanceinaninpatientdermatologyserviceduring a 10-year period. J. Am. Acad. Dermatol. 2004, 50 (6), 845–849. https://doi.org/10.1016/j.jaad.2003.11.064
3. Donlan R. M., Costerton J. W. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin. Microbiol. Rev. 2002, 15 (2), 167–193. https://doi.org/10.1128/CMR.15.2.167-193.2002
4. Negut I., Grumezescu V., Grumezescu A. M. Treatment Strategies for Infected Wounds. Molecules. 2018, 23 (9), 2392. https://doi.org/10.3390/molecules23092392
5. Pilar R. F., Emaneini M., Beigverdi R., Banar M., van Leeuwen B. W., Jabalameli F. Combinatorial effects of antibiotics and enzymes against dual-species Staphylococcus aureus and Pseudomonasae ruginosa biofilms in the wound-like medium. PloS One. 2020, 15 (6). https://doi.org/10.1371/journal.pone.0235093
6. Nordmann P., Naas T., Fortineau N., Poirel L. Superbugs in the coming new decade; multidrug resistance and prospects for treatment of Staphylococcusaureus, Enterococcus spp. And Pseudomonasae ruginosa in 2010. Curr. Opin. Microbiol. 2007, 10 (5), 436–440. https://doi.org/10.1016/j.mib.2007.07.004
7. Xu G., Zhao Y., Du L. Hfq regulates antibacterial antibiotic biosynthesis and extra cellular lytic-enzyme production in Lysobacter enzymogenes OH11. Microbiol. Biotechnol. 2015, 8 (3), 499–509. https://doi.org/10.1111/1751-7915.12246
8. Genilloud O. Current approaches to exploit actinomycetes as a source of novel natural products. J. Ind. Microbiol. Biotechnol. 2011, 38 (3), 375–389. https://doi.org/10.1007/s10295-010-0882-7
9. Gurung N., Ray S., Bose S., Vivek R. A Broader View: Microbial Enzymes and Their Relevance in Industries, Medicine, and Beyond. Biomed. Res. Int. 2013, V. 2013, P. 1–18.https://doi.org/10.1155/2013/329121
10. Chakraborty A. K. Enzybiotics, A New Class of Enzyme Antimicrobials Targeted against Multidrug-Resistant Superbugs. Nov. Appro. Drug. Des. Dev. 2017, 2 (4), 1–4. https://doi.org/10.19080/NAPDD.2017.01.555576
11. Tiwari R., Dhama K., Chakraborty S., Kapoor S. Enzybiotics: New Weapon in the Army of Antimicrobials: A Review. Asian. J. Anim. Vet. Adv. 2014, 9 (3), 144–163. https://doi.org/10.3923/ajava.2014.144.163
12. S?o-Jos? C. Engineering of Phage-Derived Lytic Enzymes: Improving Their Potentialas Antimicrobials. Antibiotics. 2018, 7 (2), 29. https://doi.org/10.3390/antibiotics7020029
13. Sudhakar G. K., Kamath V., Pai A. Enzybiotics – A Review. Int. J. Pharmacol. Res. 2013, 3 (14), 69–71. https://www.researchgate.net/publication/307681509_Enzybiotics-_A_Review
14. Zhernosekova I. V., Sokolova I. E., Kilochek T. P. Characteristic of bacteriolytic enzyme complex of Streptomyces recifensisvar. lyticus 2Р-15. Bulletin of the Institute of Agricultural Microbiology. 2000, V. 7, P. 31–32. (In Russian).
15. Todosiichuk Т. S., Pokas О. V. Specificity analysis of finished forms of antimicrobial drugs from Streptomyce salbus. Eastern European Journal of Advanced Technology. 2015, 4/6 (76), 58–61. (In Ukrainian). https://doi.org/10.15587/1729-4061.2015.47730
16. Todosiichuk T. S., Klochko V. V., Savchuk Ya. I., Kobzysta O. P. New antibiotic substances of the Streptomyce salbus enzybiotic complex. Microbiol. J. 2019, 81 (5), 62–72.https://doi.org/10.15407/microbiolj81.05.062
17. Todosiichuk T. S. The development of technology of hydrolytic enzyme preparation Cytorecifen. Ph. D. dissertation. National technical university “KSh”, National University of food technologies. Kyiv, 2000.
18. Pavlova I. N., Zholner L. G., Zakharova I. Ya. Serine proteinase with lytic properties. Microbiology. 1988, 57 (3), 398 – 404.
19. Petrova I. S., Vintsyunaite M. N. Determination of the lytic and proteolytic activity of enzyme preparations of microbialorigin. Prikl. Biochem. Microbiol.1966, V. 2, P. 322 – 327.
20. Romanova Yu. M., Alekseeva N. V., Smirnova T. A. Ability to form biofilms in artificial systems in various strains of Salmonella typhymurium. Zhurn. Microbiol. 2006, V. 4, P. 38–42.
21. Rios Colombo N. S., Chalon M. C., Navarro S. A., Bellomio A. Pediocin-like bacteriocins: new perspectives on mechanism of action and immunity. Curr. Genet. 2017, 64 (2), 27–34. https://doi.org/10.1007/s00294-017-0757-9
22. Pokas O. V., Polishchuk O. I., Todosiichuk T. S. Influence of the enzyme preparation "Cytorecifen-M" for the ability of formation the biofilms by Pseudomonasae ruginosa strains. Preventive medicine. 2011, 2 (14), 81–85.
- Details
- Hits: 1051
ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta Т. 15, No. 1, 2022
P. 61-71. Bibliography 47, Engl.
UDC: 547.915
https://doi.org/10.15407/biotech15.01.061
CYTOTOXIC, ANTIOXIDANT AND ANTIMICROBIAL ACTIVITIES OF Peganum harmala L. EXTRACTS
Dehiri Mounira 1, Diafat Abdelouahab 1, Fatmi Widad 2, Ben Mansour Riadh 3, Bouaziz Farid 1, Bahloul Ahmed 2
1 Laboratory of Characterization and Valorization of Natural Products, Faculty of Nature and Life Sciences, University El-Bachir El-Ibrahimi, Bord jBou Arreridj
2 Laboratory of Health and Environment, Faculty of Nature and Life Sciences, University El-Bachir El-Ibrahimi, Bord jBou Arreridj
3 Laboratory Analysis, Valuation of Food Securities, Biotechnology Research Group and Pathologies, National School of Engineering of Sfax (ENIS), Tunisia
Peganum harmala L., known as ?Harmel?, is a plant widely used in the traditional Algerian medicine.
Aim. The purpose of this work is to study the antioxidant, antiproliferative and antimicrobial potential of Peganum harmala extracts.
Methods. Colorimetric methods were used to quantify phenolic compounds, while the antioxidant activity was estimated in vitro using DPPH/ABTS radical scavenging assay, ferric reducing power, ?-carotene bleaching assay, total antioxidant capacity, and ferrous iron chelating assay. The agar well diffusion and the broth microdilution method were used to evaluate the antibacterial activity and the MTT assay was used to test the cytotoxicity of the extracts.
Results. The ethanolic extracts of Peganum harmala L. showed the highest polyphenols content and the potent antioxidant, gave a good activity against Gram + and Gram- bacteria and good antifungal effect and were more cytotoxic to the HeLa cell line.
Conclusions. It is concluded that selected plants could be a potential source of bioactive compounds with antioxidant, antimicrobial and antiproliferative potential. Hence, it is indicated to further investigate this plant in vitro as well as in vivo for new drug discovery.
Key words: Peganum harmala. polyphenols, antioxidant activity, antimicrobial effect, cytotoxic effect.
© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2022
References
1. Shahrajabian M. H., Sun W., Cheng Q. Clinical aspects and health benefits of ginger (Zingiber officinale) in both traditional Chinese medicine and modern industry. Acta Agr. Scand. Section B ? Soil & Plant Science. 2019, 69 (6), 1–11. https://doi.org/10.1080/09064710.2019.1606930
2. Sun W., Shahrajabian M. H., Cheng Q. Pyrethrum an organic and natural pesticide. J. Biol. Environ. Sci. 2020, 14 (40), 41–44.
3. Shahrajabian M. H., Sun W., Chen Q. Traditional herbal medicine for the prevention and treatment of cold and flu in the autumn of 2020, overlapped with COVID-19. Nat. Prod. Commun. 2020, 15 (8), 1–10. https://doi.org/10.1177/1934578X20951431
4. Gurib-Fakim A. Medicinal plants: Traditions of yesterday and drugs of tomorrow. Molecular Aspects of Medicine. 2006, 27 (1), 1–93. https://doi.org/10.1016/j.mam.2005.07.008
5. Barros H. D. Q., Junior M. R. M. Chapter 6 ? Phenolic Compound Bioavailability Using In Vitro and In Vivo Models. Bioactive Compounds. 2019, P. 113?126. https://doi.org/10.1016/B978-0-12-814774-0.00006-2
6. Ashok B. T., Ali R. The aging paradox: Free radical theory of aging. Exp. Gerontol. 1999, 34 (3), 293?303. https://doi.org/10.1016/S0531-5565(99)00005-4
7. Rahman M. M., Rahaman M. S., Islam M. R., Rahman F., Mithi F. M., Alqahtani T., Almikhlafi M. A., Alghamdi S. Q., Alruwaili A. S., Hossain M. S. Role of Phenolic Compounds in Human Disease: Current Knowledge and Future Prospects. Molecules. 2022, V. 27, P. 233. https://doi.org/10.3390/molecules27010233
8. Bu?kov? M., Pu?k?rov? A., Kal?szov? V., Kisov? Z., Pangallo D. Essential oils against multidrug resistant gram-negative bacteria. Biologia. 2018, V. 73, P. 803–808. https://doi.org/10.2478/s11756-018-0090-x
9. Ghasemi M., Ghasemi N., Azimi-Amin J. Adsorbent ability of treated Peganum harmala L. seeds for the removal of Ni (II) from aqueous solutions: kinetic, equilibrium and thermodynamic studies. Indian J. Mater. Sci. 2014. https://doi.org/10.1155/2014/459674
10. Behidj-Benyounes N., Dahmene T., Allouche N., Laddad A. Phytochemical, antibacterial and antifungal activities of alkaloids extracted from Peganum harmala (Linn.) seeds of South of Algeria. Asian J. Chem. 2014, 26 (10), 2960?2964. https://doi.org/10.14233/ajchem.2014.16138
11. Benarous K., Bombarda I., Iriepa I., Moraleda I., Gaetan H., Linani A. Harmaline and hispidin from Peganum harmala and Inonotus hispidus with binding affinity to Candida rugosa lipase: In silico and in vitro studies. Bioorg. Chem. 2015, V. 62, P. 1–7. https://doi.org/10.1016/j.bioorg.2015.06.005
12. Jalali A., Dabaghian F., Zarshenas M. M. Alkaloids of Peganum harmala: Anticancer Biomarkers with Promising Outcomes. Curr. Pharmac. Design. 2021, 27 (2), 185?196 (12). https://doi.org/10.2174/1381612826666201125103941
13. Abbas M. W., Hussain M., Qamar M., Ali S., Shafiq Z., Wilairatana P., Mubarak M. S. Antioxidant and Anti-Inflammatory Effects of Peganum harmala extracts: An In Vitro and In Vivo Study. Molecules. 2021, V. 26, P. 6084. https://doi.org/10.3390/molecules26196084
14. Keihanian F., Moohebati M., Saeidinia A., Mohajeri S. A., Madaeni S. Therapeutic effects of medicinal plants on isoproterenol-induced heart failure in rats. Biomed. Pharmacotherapy. 2021, V. 134, P. 111101. https://doi.org/10.1016/j.biopha.2020.111101
15. Arif M., WangX., Kazi M. S. K., Ullah Khan S., Saeed S., Khan A. M. Antimicrobial activities of different solvent extracts from stem and seeds of Peganum harmala L. PLoS ONE. 2022, 17 (4), e0265206. https://doi.org/10.1371/journal.pone.0265206
16. Jim?nez J., River?n-Negrete L., Abdullaev F., Espinosa-Aguirre J., Rodr?guez-Arnaiz R. Cytotoxicity of the ?-carboline alkaloids harmine and harmaline in human cell assays in vitro. Exp. Toxicol. Pathol. 2008, 60 (4), 381?389. https://doi.org/10.1016/j.etp.2007.12.003
17. Khademalhosseini A. A., Tabatabaei A., Akbari P., Fereidouni M. S., Akhlaghi M. Comparison of in vivo antiseptic and in vitro antimicrobial heffects of PeganumharmalaL. seedsethanolic extract with Butadiene. J. Coastaltyry Life Medicine. 2015, V. 3, P. 70?77.
18. Iqbal E., Salim K. A., Lim L. B. L. Phytochemical screening, total phenolic and antioxidant activities ofbark and leaf extracts of Goniothalamud velutinus (Airy Shaw) from Brunei Darussalam. J. King Saud University. 2015, V. 27, P. 224?232. https://doi.org/10.1016/j.jksus.2015.02.003
19. Mbiantcha M., Kamanyi A., Teponno R. B., Tapondjou L. A., Watcho P., Nguelefack T. B. Analgesic and Anti-Inflammatory Properties of Extracts from the Bulbils of Dioscorea bulbifera L. Var sativa. (Dioscoreaceae) in Mice and Rats. Evidence-Based Complementary and Alternative Medicine. 2011, P. 1?9. https://doi.org/10.1155/2011/912935
20. Robeson D. J., Strobel G. A. The Influence of Plant Extracts on Phytotoxin Production and Growth Rate of Alternaria helianthi. J. Phytopathol. 1986, 117 (3), 265?269. https://doi.org/10.1111/j.1439-0434.1986.tb00941.x
21. Li H. Bin, Cheng K. W., Wong C. C., Fan K. W., Chen F., Jiang Y. Evaluation of antioxidant capacity and total phenolic content of different fractions of selected microalgae. Food Chemistry. 2007, 102 (3), 771?776. https://doi.org/10.1016/j.foodchem.2006.06.022
22. Bahorun T., Gressier B., Trotin F., Brunete C., Dine T., Vasseur J., Gazin J. C., Inkas M., Uycky M., Gazin M. Oxygen species scavenging activity of phenolic extract from hawthorn fresh plant organs and pharmaceutical preparation. Arzneim Forsch. 1996, V. 46, P. 1086–1094.
23. Kosalec I., Bakmaz M., Pepeljnjak S., Vladimir-Kne?evi? S. Quantitative analysis of the flavonoids in raw propolis from northern Croatia. Acta Pharmac. 2004, V. 54, P. 65?72.
24. Prieto P., Pineda M., Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Analytical Biochemistry. 1999, 269 (2), 337?341. https://doi.org/10.1006/abio.1999.4019
25. Re R., Pellegrini N., Proteggente A., Pannala A., Yang M., Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biol. Med. 1999, 26 (9), 1231?1237. https://doi.org/10.1016/S0891-5849(98)00315-3
26. Oyaizu M. Studies on product of browning reaction prepared from glucose amine. Japanese Journal of Nutrition. 1986, V. 44, P. 307?315. https://doi.org/10.5264/eiyogakuzashi.44.307
27. Decker E. A., Welch B. Role of Ferritin as a Lipid Oxidation Catalyst in Muscle Food. J. Agric. Food Chem. 1990, 38 (3), 674?677. https://doi.org/10.1021/jf00093a019
28. Dapkevicius A., Venskutonis R., Van Beek T. A., Linssen J. P. H. Antioxidant activity of extracts obtained by different isolation procedures from some aromatic herbs grown in Lithuania. J. Sci. Food Agric. 1998, 77 (1), 140?146. https://doi.org/10.1002/(SICI)1097-0010(199805)77:1<140::AID-JSFA18>3.0.CO;2-K
29. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods. 1983, V. 65, P. 55–63. https://doi.org/10.1016/0022-1759(83)90303-4
30. NCCLS. Performance standards for antimicrobial disk susceptibility tests. Approved standard M02-A7. National Committee for Clinical Laboratory Standards. USA: Villanova. PA. 2002.
31. Kpodekon T. M., Boko C. K., Mainil G. J., Farougou S., Sessou P., Yehouenou B., Gbenou J., Duprez J. N., Bardiau M. Composition chimique et test d’efficacit? in vitro des huiles essentielles extraites de feuilles fra?ches du basilic commun (Ocimum basilicum) et du basilic tropical (Ocimum gratissimum) sur Salmonella entericas?rotype Oakland et Salmonella enterica s?rotype legon. J. de la Soci?t? Ouest-Africaine de Chimie. 2013, V. 35, P. 41?48.
32. Zainab G. K., Hafeez A., Ihsan U. I., Tofeeq U. R., Syed A. M., Shazadi I., Nighat F., Nisar U. R. Antioxidant, Antimicrobial and Antileishmanial Study of different parts of Peganum harmala. Int. J. Biosci. 2016, 9 (1), 45?58. https://doi.org/10.12692/ijb/9.1.45-58
33. Medjeldi S., Bouslama L., Benabdallah A., Essid R., Haou S., Elkahoui S. Biological activities, and phytocompounds of northwest Algeria Ajuga iva (L) extracts: Partial identification of the antibacterial fraction. Microb. Pathog. 2018, V. 121, P. 173?178. https://doi.org/10.1016/j.micpath.2018.05.022
34. Allaq A. A., Sidik N. J., Aziyah A. Z., Adewale A. I. Antioxidant, Antibacterial, and Phytochemical Screening of Ethanolic Crude Extracts of Libyan Peganum harmala Seeds. J. Pharmac. Res. Int. 2021, 33 (13), 74?82. https://doi.org/10.9734/jpri/2021/v33i1331268
35. Khadhr M., Bousta D., El Hajaji H., Lach M. Phytochemical Screening, Total Phenolics and Biological Activities of Tunisian Peganum harmala Seed Extracts. J. Chem. Pharmac. Res. 2017, 9 (2), 32?39.
36. Wang M., Li J., Rangarajan M., Shao Y., La Voie E. J., Huang T. C., Ho C. T. Antioxidative Phenolic Compounds from Sage (Salvia officinalis). J. Agric. Food Chem. 1998, 46 (12), 4869?4873. https://doi.org/10.1021/jf980614b
37. Baghiani A., Djarmouni M., Boumerfeg S., Hayet T., Charef N., Khennouf S., Arrar L. Xantine oxidase inhibition and antioxidant effects of Peganum harmala seeds extracts. Eur. J. Med. Plants. 2012, V. 2, P. 42?56.
38. Frankel E. N., Huang S. W., Kanner J., German J. B. Interfacial Phenomena in the Evaluation of Antioxidants: Bulk Oils vs Emulsions. J. Agric. Food Chem. 1994, 42 (5), 1054?1059. https://doi.org/10.1021/jf00041a0011
39. Wang C., Zhang Z., Wang Y., He X. Cytotoxic Indole Alkaloids against Human Leukemia Cell Lines from the Toxic Plant Peganum harmala. Toxins. 2015, 7 (11), 4507?4518. https://doi.org/10.3390/toxins7114507
40. Yaacob N. S., Hamzah N., Nik Mohamed Kamal N. N., Zainal Abidin S. A., Lai C. S., Navaratnam V., Norazmi M. N. Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro. BMC ComplementaryMedicine and Alternative Medicine. 2010, 10 (1), 42.https://doi.org/10.1186/1472-6882-10-42
41. Guergour H. Etude des aspects morphologiques, phytochimiques et pharmacotoxicoloqiques de la plante Peganum harmala. Universit? Ferhat Abbas S?tif. 2018, P. 73?86.
42. Biyiti L. F., Meko'o D. L., Tamzc V., Amvam Z. P. H. Recherche de l'activit? antibact?rienne de quatre plantes m?dicinales camerounaises. Pharm. M?d. Trad. Afr. 2004, V. 13, P. 11?20.
43. Faucher J. L., Avril J. L. Bact?riologie G?n?rale et M?dicale. V. 1. Paris: Ellipses. 2002
44. Djarmouni M., Boumerfeg S., Baghiani A., Boussoualim N., Zerargui F., Trabsa H. Evaluation of Antioxidant and Antibacterial Properties of Peaganum harmala Seed Extracts. 2018.
45. Arif M., Wang X., Kazi M. S. K., Ullah Khan S., Saeed S., Khan A. M. Antimicrobial activities of different solvent extracts from stemand seeds of Peganum harmala L. PLoS ONE. 2022, 17 (4), e0265206. | https://doi.org/10.1371/journal.pone.0265206
46. Berche P., Gaillard J. L., Simonet M. Les bact?ries des infections humaines. Flammarion M?decine et Sciences. 1991, 660 p. https://doi.org/10.1371/journal.pone.0265206
47. Diba K., Shoar M. G., Shabatkhori M., Khorshivand Z. Antifungal activity of alcoholic extract of Peganum harmala seeds. J. Med. Plants Res. 2011, 5 (23), 5550?5554. URL: http://www.scopus.com/inward/record.url?eid=2-s2.0
- Details
- Hits: 679
ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta Т. 15, No. 1, 2022
P. 52-60. Bibliography 31, Engl.
UDC: 616.12-005.8:577.175.82:612.82.015.38.08
https://doi.org/10.15407/biotech15.01.052
CARDIOPROTECTIVE EFFECT OF ENKEPHALINS UNDER IMMOBILIZATION STRESS
Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv, Ukraine
Objective: The aim of this study was to investigate the cardioprotective effect of dalargin, a synthetic leu-enkephalin.
Methods: The induction of myocardial infarction in rats, which were kept on a diet with excess fat and calcium/sodium salts for two months, by the use of immobilization stress. The experimental results indicated that the applied model allowed to induce the development of myocardial infarction within one three days, which was confirmed by electrocardiography, enzyme-linked immunosorbent assay and histological examination.
Results: Pre-treatment of rats with dalargin had no prevented myocardial infarction, however, it increased the resistance to immobilization stress and reduced infarction-induced myocardial lesions. Simultaneous administration of naloxone, an opiate receptor antagonist, together with dalargin eliminated its cardioprotective effect in experimental animals.
Conclusion: The use of synthetic leu-enkephalin dalargin significantly reduced the risk of myocardial infarction caused by excessive neuromuscular stress. The dalargin effect on the myocardium was mediated by opiate receptors.
Key words: myocardial infarction, immobilization stress, dalargin.
© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2022
References
1. Virani S. S., Alonso A., Aparicio H. J., Benjamin E. J., Bittencourt M. S., Callaway C. W., Carson A. P., Chamberlain A. M., Cheng S., Delling F. N., Elkind M. S. V., Evenson K. R., Ferguson J. F., Gupta D. K., Khan S. S., Kissela B. M., Knutson K. L., Lee C. D., Lewis T. T., Liu J., Loop M. S., Lutsey P. L., Ma J., Mackey J., Martin S. S., Matchar D. B., Mussolino M. E., Navaneethan S. D., Perak A. M., Roth G. A., Samad Z., Satou G. M., Schroeder E. B., Shah S. H., Shay C. M., Stokes A., VanWagner L. B., Wang N. Y., Tsao C. W. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics – 2021 Update: A Report From the American Heart Association. Circulation. 2021, 143 (8), e254-e743. https://doi.org/10.1161/CIR.0000000000000950
2. Kruglyakov P. V., Sokolova I. B., Polyntsev D. G. Cell therapy for myocardial infarction. Tsitologiya. 2008, V. 50, P. 521–528. (In Russian).
3. Gulevsky A. K., Abakumova E. S., Moiseyeva N. N. Perspectives of Application of Low-Molecular Fraction (up to 5 kDa) from Hearts of Newborn Piglets for Myocardial Regeneration. Problems of Cryobiology. 2012, V. 22, P. 320.
4. Gulevsky A. K., Grischenko V. I., Tereschenko O. S., Zagnoiko V. I., Akhremenko A. K. The effect of a (1?10 kD) brain fraction of Equus coballus of Yakut region on the kinetic parameters of Ca2+-transporting systems in cardiomyocyte sarcolemma vesicles. Cryo-Letters. 1994, V. 15, P. 27–32.
5. Maslov L. N., Lishmanov Y. B., Arbuzov A. G., Krylatov A. V., Budankova E. V., Konkovskaya Y. N., Burkova V. N., Severova E. A. Antiarrhythmic activity of phytoadaptogens in short-term ischemia-reperfusion of the heart and postinfarction cardiosclerosis. Bull. Exp. Biol. Med. 2009, V. 147, P. 303–306. https://doi.org/10.1007/s10517-009-0502-6
6. Gomes I., Dale C. S., Casten K., Geigner M. A., Gozzo F. C., Ferro E. S., Heimann A. S., Devi L. A. Hemoglobin-derived peptides as novel type of bioactive signaling molecules. AAPS J. 2010, 12 (4), 658?669. https://doi.org/10.1208/s12248-010-9217-x
7. Ziganshin R. K., Sviryaev V. I., Vas'kovskii B. V., Mikhaleva I. I., Ivanov V. T., Kokoz Y. M., Alekseev A. E., Korystova A. F., Sukhova G. S., Emel'yanova T. G., Usenko A. B. Biologically active peptides isolated from the brain of hibernating ground squirrels. Bioorg. Khim. 1994, V. 20, P. 899–918. Russian.
8. Ross A. P., Drew K. L. Potential for discovery of neuroprotective factors in serum and tissue from hibernating species. Mini Rev. Med. Chem. 2006, 6 (8), 875–884. https://doi.org/10.2174/138955706777934964
9. Kokoz Y. M., Zenchenko K. I., Alekseev A. E., Korystova A. F., Lankina D. A., Ziganshin R. H., Mikhaleva I. I., Ivanov V. T. The effect of some peptides from the hibernating brain on Ca2+ current in cardiac cells and on the activity of septal neurons. FEBS Lett. 1997, 411 (1), 71–76. https://doi.org/10.1016/S0014-5793(97)00607-8
10. Headrick J. P., See Hoe L. E., Du Toit E. F., Peart J. N. Opioid receptors and cardioprotection — opioidergic conditioning’ of the heart. Br. J. Pharmacol. 2015, V. 172, P. 2026–2050. https://doi.org/10.1111/bph.13042
11. Peart J. N., Gross E. R., Gross G. J. Effect of exogenous kappaopioid receptor activation in rat model of myocardial infarction. J. Cardiovasc. Pharmacol. 2004, V. 43, P. 410–415. https://doi.org/10.1097/00005344-200403000-00012
12. Maslov L. N., Lishmanov Y. B., Oeltgen P. R., Barzakh E. I., Krylatov A. V, Govindaswami M., Brown S. A. Activation of peripheral ?2-opioid receptors increases cardiac tolerance to ischemia/reperfusion injury: Involvement of protein kinase C, NO-synthase, K+-ATP channels and the autonomic nervous system. Life Sci. 2009, V. 84, P. 657–663. https://doi.org/10.1016/j.lfs.2009.02.016
13. Peart J. N., Gross E. R., Gross G. J. Opioid-induced preconditioning: recent advances and future perspectives. Vascul. Pharmacol. 2005, 42 (5?6). 211–218. https://doi.org/10.1016/j.vph.2005.02.003
14. Borlongan C. V., Hayashi T., Oeltgen P. R., Su T. P., Wang Y. Hibernation-like state induced by an opioid peptide protects against experimental stroke. BMC Biol. 2009, V. 7, P. 31. https://doi.org/10.1186/1741-7007-7-31
15. Kolaeva S. G., Semenova T. P., Santalova I. M., Moshkov D. A., Anoshkina I. A., Golozubova V. Effects of L-thyrosyl ? L-arginine (kyotorphin) on the behavior of rats and goldfish. Peptides. 2000, 21 (9), 1331–1336. https://doi.org/10.1016/S0196-9781(00)00275-8
16. Ignat'ev D. A., Sukhova G. S., Liashkov A. E. [Temperature and cardiotropic effects of kyotorphin and neokyotorphin in hibernating and nonhibernating animals]. Usp. Fiziol. Nauk. 2009, 40 (3), 68–88. (In Russian).
17. Perazzo J., Castanho M. A., S? Santos S. Pharmacological Potential of the Endogenous Dipeptide Kyotorphin and Selected Derivatives. Front. Pharmacol. 2017, V. 7, P. 530. https://doi.org/10.3389/fphar.2016.00530
18. Gulevsky O. K., Schenyavsky I. I. Antihypoxant Activity of Low Molecular Weight Fraction Bovine Blood Cryohemolysate at Different Stages of Ontogenesis. Problems of Cryobiology and Cryomedicin. 2017, 27 (1), 41–50. https://doi.org/10.15407/cryo27.01.041
19. Gulevsky A. K., Abakumowa E. S., Shenyavsky I. I. Biological activity of low molecular weight fraction obtained from cord and peripheral blood in cows of different ages. Fiziol. Zh. 2017, 63 (2), 73?79. https://doi.org/10.15407/fz63.02.073
20. Rohoza L. A. Biological Effect of Exract of Cryopreserved Piglet’s Heart Fragments in Ischemia and Spontaneous Myocardial Infarction. Problems of Cryobiology and Cryomedicine. 2017, 27 (2), 167. https://doi.org/10.15407/cryo27.02.167
21. Chyzh M. O., Babaieva G. G., Rohoza L. A., Halchenko S. Ye. Extract of pigs’ heart cryopreserved fragments as a regulator of state of rats heart muscle in myocardial necrosis model. Bulletin of problems biology and medicine. 2020, 4 (158), 78–83. https://doi.org/10.29254/2077-4214-2020-4-158-78-83
22. Scheniavsky I. J. Improving the model of myocardial infarction in rats. Exp. Clin. Physiol. Biochem. ECPB. 2021, 92 (1), 40–47. (In Ukrainian). https://doi.org/10.25040/ecpb2021.01-02.040
23. Ambroskina V. V., Kriachok T. A., Larionov O. P., Bratus' V. V., Talaieva T. V. Hypertrygliceridemia as a factor of atherogenesis: significance and mechanisms of action. Fiziol. Zh. 2008, 54 (5), 61–70. (In Ukrainian).
24. Seredenin S. B., Badyshtov B. A., Neznamov G. G., Makhnycheva A. L., Kolotilinskaia N. V., Nadorov S. A. Predicting individual reactions to emotional stress and benzodiazepine tranquilizers. Eksp. Klin. Farmakol. 2001, 64 (1), 3–12. (In Russian).
25. Hou Y. C., Lu C. L., Zheng C. M., Chen R. M., Lin Y. F., Liu W. C., Yen T. H., Chen R., Lu K. C. Emerging Role of Vitamins D and K in Modulating Uremic Vascular Calcification: The Aspect of Passive Calcification. Nutrients. 2019, 11 (1), 152. https://doi.org/10.3390/nu11010152
26. Rohrmann S., Garmo H., Malmstr?m H., Hammar N., Jungner I., Walldius G., Van Hemelrijck M. Association between serum calcium concentration and risk of incident and fatal cardiovascular disease in the prospective AMORIS study. Atherosclerosis. 2016, V. 251, P. 85–93. https://doi.org/10.1016/j.atherosclerosis.2016.06.004
27. Lee S. J., Lee I. K., Jeon J. H. Vascular Calcification-New Insights Into Its Mechanism. Int. J. Mol. Sci. 2020, 21 (8), 2685. https://doi.org/10.3390/ijms21082685
28. H?naut L., Candellier A., Boudot C., Grissi M., Mentaverri R., Choukroun G., Brazier M., Kamel S., Massy Z. A. New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease. Toxins (Basel). 2019, 11 (9), 529. https://doi.org/10.3390/toxins11090529
29. Wick M. R. The hematoxylin and eosin stain in anatomic pathology – An often-neglected focus of quality assurance in the laboratory. Seminars in Diagnostic Pathology. 2019, 36 (5), 303–311. https://doi.org/10.1053/j.semdp.2019.06.003
30. Shchenyavsky I. I., Gulevsky O. K. Study of Protective Effect of Synthetic Neuropeptide Dalargin Under Cold Stress. Probl. Cryobiol. Cryomed. 2019, V. 29, P. 246–254. https://doi.org/10.15407/cryo29.03.246
31. Shcheniavsky I. Anti-Apoptotic Effect of Synthetic Leu-Enkephalin Dalargin on Rat Leukocytes in Cold Stress Model in Vivo. Probl. Cryobiol. Cryomed. 2021, V. 31, P. 3–13. https://doi.org/10.15407/cryo31.01.003
- Details
- Hits: 948
ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta Т. 15, No. 1, 2022
P. 43-51. Bibliography 29, Engl.
UDC: 615.214.22.015.11
https://doi.org/10.15407/biotech15.01.043
M. Golovenko 1, A. Reder 2, V. Larionov 1, S. Andronati 1
1 Physico-Chemical Institute of the National Academy of Sciences of Ukraine, Odesa
2 SLC «INTERCHEM», Odesa, Ukraine
The aim of this study was to identify the Propoxazepam metabolites, formed by suspension of cryopreserved human hepatocytes, using the precise method of mass LC-MS/MS analysis.
Methods. A suitable chromatographic method was developed for the profiling of Propoxazepam and its metabolites. Samples were analyzed using a Waters Vion high resolution LC-MS/MS instrument, and data were examined using Waters Unifi software to determine the identity of the most abundant metabolites. Following a 4-hour incubation with human hepatocytes, intact Propoxazepam molecule accounted for 96.0% of the profile. Its most abundant metabolite was the oxidize.
Results. Propoxazepam (3-hydroxyderivative), which accounted for approximately 2.5% of the total peak response in the 4-hour sample. Two minor components were also found, each accounting for < 10% of the total peak response. Glucuronic conjugates have not been found under the experimental conditions. All metabolites formed represented less than 10% of the total chromatographic peak response.
Coclusion. The data obtained indicate the absence of reactive electrophilic derivatives among the metabolites of Propoxazepam.
Key words: Propoxazepam, humanhepatocytes, metabolism, LC-MS/MS analysis.
© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2022
References
1. Golovenko N. Ya., Voloshchuk N. I., Andronati S. A., Taran I. V., Reder А. S., Pashynska О. S., Larionov V. B. Antinociception induced by a novel benzodiazepine receptor agonist and bradykinin receptor antagonist in rodent acute and chronic pain models. Eur. J. Biomed. Pharmacol. Sci. 2018, 5 (12), 79–88.
2. Golovenko M., Larionov V., Reder A., Valivodz I., Tsapenko Z. Sedative-hypnotic and muscle relaxant activities of propoxazepam in animal models and investigation on possible mechanisms. Drug Discovery. 2020, 14 (33), 155?162.
3. Desai A., Kherallah Y., Szabo C., Marawar R. Gabapentin or pregabalin induced myoclonus: A case series and literature review. J. Clin. Neurosci. 2019, V. 61, P. 225–234. https://doi.org/10.1016/j.jocn.2018.09.019
4. Golovenko N. Ya., Larionov V. B., Andronati S. A., Valivodz` I. P., Yurpalova T. A. Рharmacodynamic analysis of propoxazepam interaction with GABA-benzodiazepine-receptor-ionophore complex. Neurophysiol. 2018, 50 (1), 2–11. https://doi.org/10.1007/s11062-018-9711-9
5. Golovenko N. Ya., Larionov V. B., Reder A. S., Valivodz I. P. An effector analysis of the interaction of propoxazepam with antagonists of GABA and glycine receptors. Neurochem. J. 2017, 11 (4), 302–308. https://doi.org/10.1134/S1819712417040043
6. Golovenko M., Reder A., Andronati S., Larionov V. Evidence for the involvement of the GABA-ergic pathway in the anticonvulsant and antinociception activity of Propoxazepam in mice and rats. J. Pre-Clin. Clin. Res. 2019, 13 (3), 99?105. https://doi.org/10.26444/jpccr/110430
7. Dambach D. M., Andrews B. A., Moulin F. New technologies and screening strategies for hepatotoxicity: use of in vitro models. Toxicol. Pathol. 2005, V. 33, P. 17–26. https://doi.org/10.1080/01926230590522284
8. Xu J. J., Henstock P. V., Dunn M. C., Smith A. R., Chabot J. R., de Graaf D. Cellular imaging predictions of clinical drug-induced liver injury. Toxicol. Sci. 2008, V. 105, P. 97–105. https://doi.org/10.1093/toxsci/kfn109
9. Chu V., Einolf H. J., Evers R. In vitro and in vivo induction of cytochrome P450: a survey of the current practices and recommendations: a Pharmaceutical Research and Manufacturers of America perspective. Drug Metab. Dispos. 2009, V. 37, P. 1339–1354. https://doi.org/10.1124/dmd.109.027029
10. McGinnity D. F., Tucker J., Trigg S., Riley R. J. Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes. Drug Metab. Dispos. 2005, V. 33, P. 1700–1707. https://doi.org/10.1124/dmd.105.005884
11. Kikkawa R., Fujikawa M., Yamamoto T., Hamada Y., Yamada H., Horii I. In vivo hepatotoxicity study of rats in comparison with in vitro hepatotoxicity screening system. J. Toxicol. Sci. 2006, V. 31, 23–34. https://doi.org/10.2131/jts.31.23
12. Reder A. S. Dispersed substance 7-bromo-5-(o-chlorophenyl)-3-propiloxy-1,2-dihydro-3H-1,4-benzodiazepine-2-one (I) with at least 50% volume fraction of particles less than 30 ?m for use as anticonvulsive and analgesic drug. Patent UA 118626.
13. Andronati S. A. Pavlovsky V. I., Golovenko M. Ya., Reder A. S., Larionov V. B., Valivodz’ I. P. Synthesis and extraction efficiency from biological fluids of [214C]Propoxazepam: a potent analgesic with multifunctional mechanism of action. JCBPS, Section A. 2019, 9 (4), 323?333. https://doi.org/10.24214/jcbps.A.9.4.32333
14. Feng W.-Y., Wen J., Stauber K. In vitro Drug Metabolism Investigation of 7-Ethoxycoumarin in Human, Monkey, Dog and Rat Hepatocytes by High Resolution LC-MS/MS. Drug Metab. Lett. 2018, 12 (1), 33?53. https://doi.org/10.2174/1872312812666180418142056
15. Shuguang Ma, Raju Subramanian. Detecting and characterizing reactive metabolites by liquid chromatography/tandem mass spectrometry. J. Mass Spectrom. 2006, V. 41. P. 1121?1139. https://doi.org/10.1002/jms.1098
16. Golovenko N. Mechanisms of xenobiotic metabolism reactions in biological membranes. Kyiv: Nauk. dumka. 1984, 220 p. (In Russian).
17. Whirl-Carrillo M., McDonagh E. M., Hebert J. M., Gong L., Sangkuhl K., Thorn C. F., Altman R. B., Klein T. E. Pharmacogenomics knowledge for personalized medicine. Clin. Pharmacol. Ther. 2012, 92 (4), 414?417. https://doi.org/10.1038/clpt.2012.96
18. Andronati S. A. Pavlovsky V. I., Golovenko M. Ya., Reder A. S., Larionov V. B., Valivodz’ I. P. Synthesis and extraction efficiency from biological fluids of [214C]Propoxazepam: a potent analgesic with multifunctional mechanism of action. JCBPS, Section A. 2019, 9 (4), 323?333. https://doi.org/10.24214/jcbps.A.9.4.32333
19. Valivodz I., Golovenko N., Larionov V. ADME properties and tentative identification of metabolites of propoxazepam in mice by radioactive carbon and UPLC-MS/MS methods. Abstracts of X International Scientific and Practical Conference. San Francisco, USA. 2020, P. 335?338.
20. Golovenko N. Y., Zinkovskii V. G., Bogatskii A. V., Sharbatyan P. A., Andronati S. A. Metabolism of phenazepam in the rat organism. Pharm. Chem. J. 1981, V. 14, P. 208?213. (In Russian). https://doi.org/10.1007/BF00777451
21. Testa B. Principles of drug metabolism. Burger’s Medicinal Chemistry, Drug Discovery, and Development. Seventh Edition, edited by Donald J. Abraham and David P. Rotella. 2010, P. 405?455. https://doi.org/10.1002/0471266949.bmc033.pub2
22. Bogatsky A. V., Zinkovsky V. G., Golovenko N. Ya. Metabolic pathways of 3H-5-bromo-2-chloro-2-amino-benzophenone in rats and mice (model of aromatic hydroxylation of phenazepam). Izvestia of the Academy of Sciences of the USSR. Ser. biological. 1983, V. 5, P. 770?776. (In Russian).
23. Bogatsky A. V., GolovenkoN. Ya., Andronati S. A., Kolomeichenko G. Yu., Zhilina Z. I. Participation of the redox chain of rat liver microsomes in the narrowing of the 1,4-benzodiazepine ring. Dokl. Academy of Sciences of the USSR. 1977, 234 (1), 215?218. (In Russian).
24. Golovenko N. Ya., Zinkovsky V. G., Andronati S. A., Yavorsky A. S. Mass spectrometric analysis of 2-aminobenzophenone derivatives and their metabolites. Bioorg. chem. 1986, V. 5, P. 686?694. (In Russian).
25. Mizuno K., Katoh M., Okumura H., Nakagawa N., Negishi T., Hashizume T., Nakajima M., Yokoi T. Metabolic Activation of Benzodiazepines by CYP3A4. Drug Metab. Dispos. 2009, 37 (2), 345–351. https://doi.org/10.1124/dmd.108.024521
26. Olsson R., Zettergren L. Anticonvulsant-induced liver damage. Am. J. Gastroenterol. 1988, V. 83, P. 576–577. https://doi.org/10.1590/S0074-02761988000500070
27. Kedderis G. L., Argenbright L. S., Miwa G. T. Covalent interaction of 5-nitroimidazoles with DNA and protein in vitro: mechanism of reductive activation. Chem. Res. Toxicol. 1989, 2 (3), P. 146–149. https://doi.org/10.1021/tx00009a004
28. Golovenko N. Ya., Kovalenko V. N., Larionov V. B., Reder A. S. Dose and time-dependent acute and sub-chronic oral toxicity study of propoxazepam in mice and rats. EAS J. Pharmacy Pharmacol. 2020, 8 (1), 1?7. https://doi.org/10.14419/ijpt.v8i1.29531
29. Golovenko M., Larionov V., Reder A. Investigation of safety profile of propoxazepam by Salmonella/Microsome test. Information, its impact on social and technical processes. Abstracts of VIII International Scientific and Practical Conference. SH SCW "NEW ROUTE" Haifa, Israel. 2020, P. 162?164.
- Details
- Hits: 1106
ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta Т. 15, No. 1, 2022
P. 23-42. Bibliography 125, Engl.
UDC: 519.8.612.007
https://doi.org/10.15407/biotech15.01.023
MATHEMATICAL MODELS OF HUMAN RESPIRATORY AND BLOOD CIRCULATORY SYSTEMS
N. I. Aralova 1, O. M. Klyuchko 2, V. I. Mashkin1, I. V. Mashkina 3, P. A. Radziejowski 4, M. P. Radziejowski 5
1 V. M. Glushkov Institute of Cybernetics of the National Academy of Sciences of Ukraine, Kyiv
2National Aviation University Kyiv, Ukraine
3Boris Grinhenko Kiyv University, Ukraine
4Kazimiera Milanowska College of Education and Therapy , Poznan, Poland
5Czestochowa University of Technology, Czestochowa, Poland
Aim. To analyze modern approaches to mathematical modeling of human respiratory and blood circulatory systems.
Methods. Comprehensive review of scientific literature sources extracted from domestic and international resources databases.
Results. Historical information and modern data concerning mathematical modeling of human functional respiratory and blood circulatory systems were summarized and analyzed in present ¬review; current trends in approaches to the construction of these models were revealed.
Conclusions. Currently, two main approaches to the mathematical modeling of respiratory and blood circulatory systems exist. One of them is the construction of models of the mechanics of respiration and blood circulation. They are based on the models of mechanics of solid deformable body, thermomechanics, hydromechanics, and continuum mechanics. This approach uses complex mathematical apparatus, including Navier-Stokes equation, which makes it possible to obtain a number of theoretical results, but it is hardly usable for real problems solutions at present time. The second approach is based on the model of F. Grodins, who represented the process of breathing as a controlled dynamic system, described by ordinary differential equations, in which the process control is carried out according to the feedback principle. There is a significant number of modifications of this model, which made it possible to simulate various disturbing influences, such as physical activity, hypoxia and hyperemia, and to predict parameters characterizing functional respiratory system under these disturbing influences.
Key words: mathematical model of respiratory system, mathematical model of blood circulatory system, hypoxic state, theoretical analysis.
© Інститут біохімії ім. О. В. Палладіна НАН України, 2022
References
1. Voropaeva O. F., Shokin Yu. I. Numerical modeling in medicine. Some Statements of Problems and Results of Calculations. Computing technologies. 2012, 17 (4), 29–55. (In Russian).
2. Regier S. A. Lectures on biological mechanics. Moskva: MGU. 1980. (In Russian). ISBN: 978-3-319-41075-3
3. Bailey N. T. G. The mathematical approach to biology and medicine. John Wiley and Sons. London–New York–Sydney. 1967, 296 p. https://doi.org/10.1002/bimj.19690110325
4. Caro C. G., Pedley T. J., Schroter R. C., Seed W. A. The mechanics of the circulation 2nd edition. Cambridge University Press. 2011, 524 p. https://doi.org/10.1017/CBO9781139013406
5. Pedley T. J. The Fluid Mechanics of Large Blood Vessels Cambridge University Press. 1980, 446 p. https://doi.org/10.1017/CBO9780511896996
6. Marchuk G. I. Mathematical models in immunology. Springer. 351 p. ISBN-13:? 978-0387909011
7. Remizov A. N. Medical and biological physics. Moskva: Higher school. 1987, 638 p. (In Russian). ISBN 978-5-9704-5943-0
8. Reznichenko G. Yu. Lectures on mathematical models in biology. RHD. 2011, 560 p. (In Russian). ISBN 978-5-93972-847-8
9. Makarov I. M. Informatics and medicine. Moskva: Science. 1997, 208 p. (In Russian).
10. Computer models and progress in medicine. Ed. O. M. Belotserkovsky, A. S. Kholodov. Moskva: Science. 2001, 300 p. (In Russian). ISBN 5-02-008371-2
11. Medicine in the mirror of informatics. Ed. O. M. Belotserkovsky, A. S. Kholodov. Moskva: Science. 2008, 242 p. (In Russian).
12. Begun P. I., Afonini P. N. Modeling in biomechanics. Moskva: Higher school. 2004, 389 p. (In Russian). ISBN 5-06-004798-9
13. Smolyaninov V. V. Mathematical models of biological tissues. Moskva: Science. 1980, 368 p. (In Russian).
14. Romanovsky Yu. M., Stepanov N. V., Chernavsky D. S. Mathematical biophysics. Moskva: Science. 1984, 304 p. (In Russian).
15. Systems computer biology. Ed. N A. Kolchanova, S. S. Goncharova, V. A. Likhoshvaya, V. A. Ivanisenko. Novosibirsk: Publishing House of the SO RAN. 2008, 769 p. (In Russian). ISBN 978-5-7692-0871-3
16. Circulatory system and arterial hypertension: Biophysical and genetic-physiological mechanisms, mathematical and computer research. Ed. L. N. Ivanova, A. M. Blokhin, A. L. Markel. Novosibirsk: Publishing House of the SO RAN. 2008, 252 p. (In Russian). ISBN 978-5-7692-1021-1
17. Sudakov K. V., Andrianov V. V., Vagin Yu. I., Kiselev I. I. Human physiology. Atlas of dynamic schemes. Moskva: GEOTAR-Media. 2009, 416 p. (In Russian). ISBN 978-5-9704-3234-1
18. Fundamental Medical and Engineering Investigations on Protective Artificial Respiration. A Collection of Papers from the DFG funded Research Program PAR (Notes on Numerical Fluids Mechanics and Multidisciplinary Desig. V. 116). Eds. M. Klaas, E. Koch, W. Schr?der. Springer-Verlag. 2011, 186 p. https://doi.org/10.1007/978-3-642-20326-8
19. Petrov I. B. Mathematical modeling in medicine and biology based on models of continuum mechanics. Proceedings of the Moscow Institute of Physics and Technology. 2009, 1 (1), 5–16. (In Russian).
20. Keener J., Sneyd J. Mathematical physiology. Springer. 2001, 766 p. https://doi.org/10.1007/978-0-387-75847-3
21. Anokhin P. K. Fundamental questions of the general theory of functional systems. Principles of systemic organization of functions. Moskva: Nauka. 1973, 258 p. (In Russian).
22. Anokhin P. K. Essays on the physiology of functional systems. Moskva: Medicine. 1975, 447 p. (In Russian).
23. Meerson F. Z., Golubeva L. Yu., Dvoryantsev S. N., Khatkevich A. N. Adaptation to hypoxia, unlike adaptation to stress, fails to protect the isolated heart from reperfusion after total ischemia (An NMR study). Bull. Exp. Biol. Med. 1995, 120 (5), 1103–1106. https://doi.org/10.1007/BF02445476
24. Meerson F. Z., Pshennikova M. G. Adaptation to stressed situations and physical loadings. Moskva: Medicina. 1988, 256 p. (In Russian). ISBN 5-225-00115-7
25. Onopchuk Yu. N., Beloshitsky P. V., Aralova N. I. To the question of the reliability of functional organism systems. Kibernetika i vy?islitelna? tehnika. 1999, Is. 122, P. 72–82. (In Russian).
26. Beloshitsky P. V., Onopchuk Yu. M., Aralova N. I. Mathematical methods for the investigation of the problem of organism functioning reliability at extreme high mountains conditions Physiol. J. 2003, 49 (3), 47–54. (In Russian). ISSN 0201-8489
27. Aralova N. I., Klyuchko O. M., Mashkin V. I., Mashkina I. V. Software for the reliability investigation of operator professional activity for “human-machine” systems. Electronics and control systems. 2017, V. 1, P. 107–115. https://doi.org/10.18372/1990-5548.51.11712
28. Balanter B. I. Introduction to mathematical modeling of pathological processes. Moskva: Medicine. 1980, 262 p.
29. Bobryakova I. L. The sensitivity of the mathematical model and the optimality of the regulation of the functional respiratory system. Diss. Candidate of Physics and Mathematics Sciences. Kyiv. 2000, 179 p. (In Russian).
30. Aralova N. I. Mathematical models of functional respiratory system for solving the applied problems in occupational medicine and sports. Saarbr?cken: LAP LAMBERT Academic Publishing GmbH & Co, KG. 2019, 368 p. (In Russian). ISBN 978-613-4-97998-6
31. Onopchuk Yu. N. On one general scheme of regulation of external respiration regimes, minute volume of blood and tissue blood flow in response to oxygen demand. Cybernetics. 1980, V. 6, P. 110–115.
32. Khanin M. A. Extreme principles in biology and medicine. Moskva: Nauka. 1978, 256 p. (In Russian).
33. Poon Chi-Sang, Ji Xin-Bao. Resolution of pulmonary ventilation-perfusion distribution recovered by enforced smoothing. Proc. 15th Annu. Northhest. Bioeng.Conf., Boston, Mass., March 27–28, 1989. New York (N. Y.). 1989, V. 3, P. 135–136. https://doi.org /10.1109/NEBC.1989.36737
34. De Lazzaria C., Darowski M., Ferraria G., Clementea F., Guaragnoa M. Computer simulation of haemodynamic parameters changes with left ventricle assist device and mechanical ventilation. Computers in Biology and Medicine. 2000, 30 (2), 55–69. https://doi.org/10.1016/S0010-4825(99)00026-8
35. H?m?lainen J. J. Optimal arterial resistance for normal and failing heart. Proc. Annu. Int. Conf. IEEE Eng. 1991. https://doi.org/10.1109/IEMBS.1991.684884
36. Karam Elie H. Modelling of cardiac growth and hypertrophy: regulating factors. Ann. Biomed. Eng. 1993, 21 (3), 309–310. https://doi.org/10.1007/BF02368187
37. Dietmar P. F. M?ller: Introduction to Transportation Analysis, Modeling and Simulation - Computational Foundations and Multimodal Applications. Simulation Foundations, Methods and Applications. Springer. 2014, P. 1–334. ISBN 978-1-4471-5636-9
38. Sherman T. F., Popel A. S., Koller A., Johnson P. C. The cost of departure from optimal radii in microvascular networks. J. Theor. Biol. 1989, 136 (6), 245–265. https://doi.org/10.1016/S0022-5193(89)80162-6
39. Bukharov I. B. Optimal structural and functional organization of circulatory and external respiration systems. Mathematical modeling. 2005, 17 (9), 3–26. (In Russian).
40. Fursova I. V. Extreme principles in mathematical biology. Advances in modern biology. 2003, 123 (2), 115–117. (In Russian).
41. Mezentseva L. V., Pertsov S. S. Mathematical modeling in biomedicine. Bulletin of new medical technologies. 2013, XX (1), 11–14. (In Russian). https://doi.org/10.24411/issn.2075-4094
42. Grodins F. Theory of regulation and biological systems. Moskva: Mir. 1966, 315 p. (In Russian).
43. Lyubimov G. A., Steklov V. A. Models of the human lungs and the study of the mechanics of breathing with their help. Proceedings of the Mathematical Institute. 1998, V. 223, P. 196–206. (In Russian).
44. Kholodov A. S. Some dynamical models of external breathing and blood circulation regarding to their interaction and substances transfer. Computational Models and Medical Progress. 2001, P. 127–163.
45. Simakov S. S., Kholodov A. S. Computational study of oxygen concentration in human blood under low frequency disturbances. Mathematical Models and Computer Simulations. Springer. 2009, 1 (2), 283. https://doi.org/10.1134/S2070048209020112
46. Ben-Tal A. Simplified models for gas exchange in the human lungs. J. Theor. Biol. 2006, V. 238, P. 474–495. https://doi.org/10.1016/j.jtbi.2005.06.005
47. Benallal H., Beck K. C., Jonson B. D., Busso T. Evaluation of cardiac output from a tidally ventilated homogeneous lung model. Eur. J. Appl. Physiol. 2005, V. 95, P. 153–162. https://doi.org/10.1007/s00421-005-1376-6
48. Kuwahara F., Sano Y., Liu J., Nakayama A. A. Porois Media Approach for Bifurcating Flow aqnd Mass Transfer in a Human Lung. J. Heat Transfer. 2009, (131) 10. https://doi.org/10.1115/1.3180699
49. Weibel E. R. Morphometry of the human lungs. Moskva: Medicine. 1970, 175 p. (In Russian).
50. Misyura A. G. Modeling the mechanisms of alveolar ventilation disorders. Cybernetics and computer technology. 1987, V. 74, P. 51–55. (In Russian).
51. Reis A. H., Miguel A. F., Aydin M. Constructal theory of flow architecture of the lungs. J. Med. Physics. 2004, V. 31, P. 1135–1140. https://doi.org/10.1118/1.1705443
52. Trusov P. V., Zaitseva N. V., Tsinker M. Yu. Modeling of human breath: conceptual and mathematical statements. Math. Biol. Bioinf. 2016, 11 (1), 64–80. https://doi.org/10.17537/2016.11.64
53. Dyachenko A. I. Study of a one-component model of lung mechanics. Medical biomechanics. 1986, V. 1, P. 147–152. (In Russian).
54. Chen X. B., Leong S. C., Lee H. P., Chong V. F., Wang D. Y. Aerodynamic effects of inferior turbinate surgery on nasal airflow--a computational fluid dynamics model. Rhinology. 2010, 48 (4), 394–400. https://doi.org/10.4193/Rhino09.196
55. Doorly D. J., Taylor D. J., Gambaruto A. M., Schroter R. C., Tolley N. Nasal Architecture form and flow. Phil. Trans. R. Soc. A. 2008, V. 386, P. 3225–3246. https://doi.org/10.1098/rsta.2008.0083
56. Fomin V. M., Vetlutsky V. M., Ganimedov V. L., Muchnaya M. I., Shepelenko V. I., Melnikov M. N., Savina A. A. Investigation of air flow in the human nasal cavity. Prikl. Mechanics Tech. Physics. 2010, 51 (2), 107–115. (In Russian). https://doi.org/10.1007/s10808-010-0033-y
57. Jiayao Yuan. Alveolar Tissue Fibers and Surfactant Effects on Lung Mechanics – Model Development and Validation on ARDS and IPF Patients January 2021IEEE. Open J. Engineering in Medicine and Biology PP. 1999, V. 1. https://doi.org/10.1109/OJEMB.2021.3053841
58. Gattinoni L., Chiumello D., Rossi S. COVID-19 pneumonia: ARDS or not? Crit. Care. 2020, 24 (1), 154. https://doi.org/10.1186/s13054-020-02880-z
59. Popovi? N., Naumovi? M., Roganovi? S. Basics of mathematical modeling of pulmonary ventilation mechanics and gas exchange. In: Badnjevic A. (eds) CMBEBIH 2017. IFMBE Proceedings. Springer, Singapore. 2017, V. 62. https://doi.org/10.1007/978-981-10-4166-2_55
60. Khoo M. C. K. Physiological Control Systems. IEEE Press series on biomedical engineering. Wiley. 1999, 344 p. ISBN-13: 978-0780334083, ISBN-10: 0780334086
61. Timischl-Teschl S., Batzel J., Kappel F. Modeling the Control of the Human Cardiovascular-Respiratory System: An Optimal Control Approach with Application to the Transition to Non-Rem Sleep. Mathematical Biosciences and Engineering. 2004. http://math.asu.edu/~mbe.
62. Milhorn H. T., Benton H., Ross H., Guyton A. C. A mathematical model of the human respiratory control system. Biophys. J. 1965, V. 5, P. 27–46. https://doi.org/10.1016/S0006-3495(65)86701-7
63. Batzel J., Fink M., Schneditz D., eds. Proceedings of the Workshop on Cardiovascular-Respiratory Control Modeling, University of Graz, Austria, June 14–16. 2001, 366 p. ISBN: 978-3-642-32882-4
64. Guyton A. C., Hall J. E. Medicinska fiziologija.Zagreb. 2012, 186 p. ISBN 978-953-176-785-9
65. Hernandez A. M., Ma?anas M. A., Costa-Castello R. Learning Respiratory System Function in BME Studies by Means of a Virtual Laboratory: RespiLab. IEEE Transactions on Education. 2008, 51 (1), 24–34. https://doi.org/10.1109/TE.2007.893355
66. Hernandez A. M., Herrera G. P., Ma?anas M. A., Costa-Castello R. Cardiolab: A Virtual Laboratory for the analysis of Human Circulatory System. 2009, 51 (1), 24–34.https://doi.org/10.1109/TE.2007.893355
67. Ben-Tal A., Tawhai M. H. Integrative approaches for modeling regulation and function of the respiratory system. WIREs Syst. Biol. Med. 2013, V. 5, P. 687–699. https://doi.org/10.1002/wsbm.1244
68. MacIntyre N. R. Respiratory System Simulations and Modeling. Respir. Care. 2004, 49 (4), 401–408. PMID: 15030613
69. Cheng L., Ivanova O., Fan H. H., Khoo M. C. An integrative model of respiratory and cardiovascular control in sleep-disordered breathing, Respir. Physiol. Neurobiol. 2010, V. 174, P. 4–28, https://doi.org/10.1016/j.resp.2010.06.001
70. O'Connor R., Segers L. S., Morris K. F., Nuding S. C., Pitts T., Bolser D. C., Davenport P. W., Lindsey B. G. A joint computational respiratory neural network-biomechanical model for breathing and airway defensive behaviors. Frontiers in Physiology. 2012, V. 3, P. 264. https://doi.org/10.3389/fphys.2012.00264
71. Ben-Tal A., Smith J. C. Control of breathing: two types of delays studied in an integrated model of the respiratory system. Respir. Physiol. Neurobiol. 2010, V. 170, P. 103–112. https://doi.org/10.1016/j.resp.2009.10.008
72. Lu K., Clark J. W. Jr., Ghorbel F. H., Ware D. L. Whole-body gas exchange in human predicted by a cardiopulmonary mode. Cardiovascular Engineering. 2003, 8 (3), 1–19. https://doi.org/10.1016/j.jtbi.2007.12.018
73. Molkov Y. I., Shevtsova N. A., Park C., Ben-Tal A., Smith J. C., Rubin J. E., Rybak I. A. A Closed-Loop Model of the Respiratory System: Focus on Hypercapnia and Active Expiration. PLoS ONE. 2014, 9 (10), e109894. https://doi.org/10.1371/journal.pone.0109894
74. Molkov Y. I., Bacak B. J., Dick T. E., Rybak I. A. Control of breathing by interacting pontine and pulmonary feedback loops. Frontiers in Neural Circuits. 2013, 7 (16), 342–357. https://doi.org/10.3389/fncir.2013.00016
75. Srinivas P., Rao P. D. P. Steady state and stability analysis of respiratory control system using LabView. Int. J. Control Theory and Computer Modelling (IJCTCM). 2012, 2 (6). https://doi.org/10.5121/ijctcm.2012.2602
76. Kappel F. Modeling the Dynamics of the Cardiovascular-respiratory System (CVRS) in Humans, a Survey. Math. Model. Nat. Phenom. 2012, 7 (5), 65–77.
https://doi.org/10.1051/mmnp/20127506
77. Lee R. M., Chiu H. L. Mathematical Model of Interactive Respiration/Cardiovascular Composite System, Int. Conference on Trends in Mechanical and Industrial Engineering (ICTMIE’2011). Bangkok. 2011, P. 55–67.
78. Maury B. The Respiratory System in Equations. Springer. 2013, P. 300, 978–8847052130. (hal-00929739). https://doi.org/10.1007/978-88-470-5214-7
79. Simakov S. S. Modern methods of mathematical modeling: of blood flow using reduced order methods. Computer Research and Modeling. 2018, 10 (5), 581–604. https://doi.org/10.20537/2076-7633-2018-10-5-581-604
80. Abakumov M. V., Gavrilyuk K. V., Esikova N. B., Koshelev V. B., Lukshin A. B., Mukhin S. I., Sosnin N. V., Tishkin V. F., Favorsky A. P. Mathematical model of hemodynamics cardiovascular system. Differencial Equations. 1997, 33 (7), 892–898. (In Russian).
81. Abakumov M. V., Ashmetkov I. V., Esikova N. B., Koshelev V. B., Mukhin S. I., Sosnin N. V., Tishkin V. F., Favorskii A. P., Khrulenko A. B. Strategy of mathematical cardiovascular system modeling. Matematicheskoe modelirovanie. 2000, 12 (2), 106–117. (In Russian).
82. Simakov S. S. Modern methods of mathematical modeling of blood flow using reduced order methods. Computer Research and Modeling. 2018, 10 (5), 581–604 https://doi.org/10.20537/2076-7633-2018-10-5-581-604
83. Mukhin S. I., Menyailova M. A., Sosnin N. V., Favorsky A. P. Analytical study of stationary hemodynamic flows in an elastic tube, taking into account friction. Dif. equations. 2007, 43 (7), 987–992. (In Russian). https://doi.org/10.1134/S0012266107070142
84. Kiselev I. N., Semisalov B. V., Biberdorf E. A., Sharipov R. N., Blokhin A. M., Kolpakov F. A. Modular modeling of the human cardiovascular system. Mathematical Biology and Bioinformatics. 2012, 7 (2), 703–736. (In Russian). https://doi.org/10.17537/2012.7.703
85. Kolpakov F. A., Sharapov R. N., Evshin E. S. Computer modeling of the circulatory system. The circulatory system and arterial hypertension. Biophysical and genetic-physiological mechanisms, mathematical and computer modeling. Ed. L. N. Ivanova, A. M. Blokhin. A. L. Markel. Novosibirsk: Publishing House of the SO RAN. 2008, P. 135–204. (In Russian).
86. Semisalov B. P. Construction and analysis of a complex model of the human cardiovascular system, including biophysical and biochemical blocks. Bulletin of NGU. Maths. Mechanics. Informatics. 2010, 10 (1), 95–107. (In Russian). http://mi.mathnet.ru/rus/vngu/v10/i1/p95
87. Medvedev A. E., Samsonov V. I., Fomin V. M. Mathematical modeling of blood flow in vessels. The circulatory system and arterial hypertension. Biophysical and genetic-physiological mechanisms, mathematical and computer modeling. Ed. L. N. Ivanova, A. M. Blokhin, A. L. Markel. Novosibirsk: Publishing House of the SO RAN. 2008, P. 80–105. (In Russian). https://www.researchgate.net/publication/287284650_Mathematical_modeling_of_the_blood_flow_in_blood_vessels
88. Sung C., Kiris C., Kwak D., David T. Numerical Models of Human Circulatory System under Altered Gravity: Brain Circulation. AIAA Paper. 2004, No 1092, 12 p. https://doi.org/ 10.2514/6.2004-1092
89. Waters S. L., Alastruby J., Beard D. A., Bovendeerd P. H., Davies P. F., Jayaraman G., Jensen O. E., Lee J., Parker K. H., Popel A. S., Secomb T. W., Siebes M., Sherwin S. J., Shipley R. J., Smith N. P., van de Vosse F. N. Review. Theoretical models for coronary vascular biomechanics. Progree & Challenges. Progress in Biophysics and Molecular Biology. 2011, V. 104. P. 49–76. https://doi.org/10.1016/j.pbiomolbio.2010.10.001
90. Quarteroni A., Rozza G. Reduced order methods for modeling and computational reduction. Springer International Publishing. 2014, 334 p. ISBN: 978-3-319-02090-7
91. Formaggia L., Quarteroni A., Veneziani A. Cardiovascular mathematics. Springer, Heidelberg. 2009, V. 1, 552 p. ISBN: 978-88-470-1152-6
92. Blanco R. A., Feijoo R. A. A 3D-1D-0D computational model for the entire cardiovascular system. Computational Mechanics. Eds. E. Dvorking, M. Goldschmidt, M. Storti. 2010, V, XXIX, 5887–5911. ISSN 2591-3522
93. Xiao N., Alastruey-Arimon J., Figueroa C. A. A systematic comparison between 1D and 3D hemodynamics in compliant arterial models. Int. J. Numer. Method Biomed. Eng. 2014, 30 (2). 204–231. https://doi.org/10.1002/cnm.2598
94. Sazonov I., Khir A. W., Hacham W. S., Boileau E., Carson J. M., van Loon R., Ferguson C., Nithiarasu P. A novel method for non-invasively detecting the severity and location of aortic aneurisms. Biomechanics and Modeling in Mechanobiology. 2017, V. 16, P. 1225–1242. https://doi.org/10.1007/s10237-017-0884-8
95. Liu J., Yan Z., Pu Y., Shiu W. S., Wu J., Chen R., Leng X., Qin H., Liu X., Jia B., Song L., Wang Y., Miao Z., Wang Y., Liu L., Cai X. C. Functional assessment of cerebral artery stenosis: A pilot study based on computational fluid dynamics. J. Cereb. Blood Flow Metab. 2017, 37 (7), 2567–2576. https://doi.org/10.1177/0271678X16671321
96. Khe A. K., Cherevko A. A., Chupakhin A. P., Bobkova M. S., Krivoshapkin A. L., Orlov K. Yu. Haemodynamics of giant cerebral aneurysm: A comparison between the rigid-wall, one-way and two-way FSI models. J. Phys.: Conf. Ser. 2016, V. 722, P. 012042. https://doi.org/10.1088/1742-6596/722/1/012042
97. Donina Zh. A. Intersystem relationships of respiration and circulation. Human Physiology. 2011, 37 (2), 117–128. (In Russian). https://doi.org/10.1134/S0362119711020034
98. Gamilov T. D. Mathematical modeling of blood flow under mechanical effects on the vessels. Diss. Cand. Phys.-Math. Sciences. 05.13.18 mathematical modeling, numerical methods and software packages. Moscow, MIPT. 2017, 157 p. (In Russian).
99. Timischl S. A Global Model for the Cardiovascular and Respiratory System. Dissertation presented to the Faculty for Natural Sciences, Karl-Franzens University of Graz,in partial fulfillment of the requirements for the degree Doktor Rerum Naturalium. 1998, 115 p.
100. Khoo M. C. K. ARMA modeling of gas exchange during spontaneous breathing. Proc. 9th Annu. Conf. IEEE Eng. Med. and Biol. Soc., Boston, Mass., 1987, Nov. 13–16. New York. 1987, V. 4, P. 2060–2061.
101. Kolchynskaja A. Z., Dudarev V. P., Kerefov M. T. Secondary tissue hypoxia. Ed. Kolchinskaya A. Z. Kyiv, Nauk. dumka. 1983, 253 p. (In Russian).
102. Albanese A., Cheng L., Ursino M., Chbat N. W. An integrated mathematical model of the human cardiopulmonary system: model development. Am. J. Physiol. Heart Circ. Physiol. 2016, 310 (7), H899?921. https://doi.org/10.1152/ajpheart.00230.2014
103. Cheng L., Albanese A., Ursino M., Chbat N. W. An integrated mathematical model of the human cardiopulmonary system: model validation under hypercapnia and hypoxia. Am. J. Physiol. Heart Circ. Physiol. 2016, 310 (7), H922?937. https://doi.org/10.1152/ajpheart.00923.2014
104. Topor Z. L., Pawlicki M., Remmers J. E. A computational model of the human respiratory control system: responses to hypoxia and hypercapnia. Ann. Biomed. Eng. 2004, 32 (11), 1530–1545. https://doi.org/10.1114/B:ABME.0000049037.65204.4c
105. Grodins F. S., Buell J., Bart A. J. Mathematical analysis and digital simulation of the respiratory control system. J. Appl. Physiol. 1967, 22 (2), 260–76. https://doi.org/10.1152/jappl.1967.22.2.260
106. Wolf M. B., Garner R. P. A mathematical model of human respiration at altitude. Ann. Biomed. Eng. 2007, 35 (11), 2003?2022. https://doi.org/10.1007/s10439-007-9361-3
107. Chiari L., Avanzolini G., Ursino M. A comprehensive simulator of the human respiratory system: validation with experimental and simulated data. Ann. Biomed. Eng. 1997, 25 (6), 985–999. PMID: 9395044 https://doi.org/10.1007/BF02684134
108. Fresiello L., Meyns B., Di Molfetta A., Ferrari G. A Model of the Cardiorespiratory Response to Aerobic Exercise in Healthy and Heart Failure Conditions. Front. Physiol. 2016, 8 (7), 189. https://doi.org/10.3389/fphys.2016.00189
109. Magosso E., Ursino M. Cardiovascular response to dynamic aerobic exercise: a mathematical model. Med. Biol. Eng. Comput. 2002, 40 (6), 660–674.https://doi.org/10.1007/BF02345305
110. Sarmiento C. A., Hern?ndez A. M., Serna L. Y., Ma?anas M. ?. An integrated mathematical model of the cardiovascular and respiratory response to exercise: model-building and comparison with reported models. Am. J. Physiol. Heart Circ. Physiol. 2021, 320 (4), H1235–H1260. https://doi.org/10.1152/ajpheart.00074.2020
111. Iconaru E. I., Georgescu L., Ciucurel C. A mathematical modelling analysis of the response of blood pressure and heart rate to submaximal exercise. Acta Cardiol. 2019, 74 (3), 198–205. https://doi.org/10.1080/00015385.2018.1478241
112. Magosso E., Ursino M. A mathematical model of CO2 effect on cardiovascular regulation. Am. J. Physiol. Heart Circ. Physiol. 2001, 281 (5), H2036?2052. https://doi.org/10.1152/ajpheart.2001.281.5.H2036
113. Ursino M., Magosso E., Avanzolini G. An integrated model of the human ventilatory control system: the response to hypoxia. Clin. Physiol. 2001, 21 (4), 465–477.https://doi.org/10.1046/j.1365-2281.2001.00350.x
114. Serna L. Y., Ma?anas M. A., Hern?ndez A. M., Rabinovich R. A. An Improved Dynamic Model for the Respiratory Response to Exercise. Front. Physiol. 2018, 7 (9), 69. https://doi.org/10.3389/fphys.2018.00069
115. Curcio L., D'Orsi L., De Gaetano A. Seven Mathematical Models of Hemorrhagic Shock. Comput. Math. Methods Med. 2021, Jun 3, 6640638. https://doi.org/10.1155/2021/6640638
116.Curcio L., D'Orsi L., Cibella F., Wagnert-Avraham L., Nachman D., De Gaetano A. A Simple Cardiovascular Model for the Study of Hemorrhagic Shock. Comput. Math. Methods Med. 2020, Dec 24, 7936895. https://doi.org/10.1155/2020/7936895
117. Curcio L., Cusimano V., D'Orsi L., Yokrattanasak J., Gaetano A. Comparison between two different cardiovascular models during a hemorrhagic shock scenario. Math. Biosci. Eng. 2020, 17 (5), 5027?5058. https://doi.org/10.3934/mbe.2020272
118. Lauer N. B., Kolchinskaya A. Z. About the oxygen organism regime Oxygen organism regime and its regulation. Kyiv: Nauk. dumka. 1966, P. 157–200. (In Russian).
119. Kolchinskaya A. Z. Oxygen regimes of organism of a child and a teenager. Kyiv: Nauk. dumka. 1973, 320 p. (In Russian).
120. Klyuchko O. M., Aralova N. I., Aralova A. A. Electronic automated work places for biological investigations Biotechnol. acta. 2019, 12 (2), 5?26. https://doi.org/10.15407/biotech12.02.005
121. Radziejowska M., Moiseyenko Y., Radziejowski P., Zych M. Oxygen Supply System Management in an Overweight Adult after 12 Months in Antarctica-Study Case. Int. J. Environ. Res. Public Health. 2021, 18 (8), 4077. https://doi.org/10.3390/ijerph18084077
122. Onopchuk Yu. N. Homeostasis of functional respiratory system as a result of intersystem and system-medium informational interaction. Bioecomedicine. Uniform information space. Ed. by V. I. Gritsenko. Kyiv. 2001, P. 59–84. (In Russian).
123. Onopchuk Yu. N. Homeostasis of the functional circulatory system as a result of intersystem and system-medium informational interaction. Bioecomedicine. Uniform information space. Ed. by V. I. Gritsenko. Kyiv. 2001, P. 85–104. (In Russian).
124. Polynkevich K. B., Onopchuk Yu. N. Conflict situations at regulating of the main function of organism respiratory system and mathematical models of their resolution. Cybernetics. 1986, V. 3, P. 100?104. Kyiv: Nauk. dumka. (In Russian). https://doi.org/10.1007/BF01069979
125. Onopchuck Y. N., Mysyura A. G. Methods of mathematical modeling and management in theoretical investigations and solutions of applied tasks of sportive medicine and physiology. Sportivna medicina. 2008, No. 1. (In Russian).