Influence of sodium desoxyribonucleate on anti-infectious protection and hematopoiesis in patients with polytrauma (randomized prospective, double-blind, placebo-controlled study)
https://doi.org/10.15789/1563-0625-IOS-1923
Abstract
The aim of the study was to evaluate the effect of sodium deoxyribonucleate on anti-infectious resistance and hematopoiesis in patients with polytraumas. A single-center study of sodium deoxyribonucleate effectiveness approved by the local Ethics Committee (protocol No. 4 05/18/2016), was conducted in 54 patients with polytrauma. The main group included 27 people, at the mean age of 39 (29-51) years old; ISS severity score, 26 (22-34). The comparison group comprised 27 people, mean age, 40 years old (26-53), mean ISS severity score was 25 points (20 to 29). The patients with randomly attributed even numbers were injected with 5 ml preparation from vials of even-numbered series, the patients with odd numbers were treated with preparation from the odd-numbered series. They were injected intramuscularly daily from day 1 to day 10 after the injury. Before treatment, as well as on days 8, 15 after injury, peripheral blood was examined for leukocyte, erythrocyte counts, hemoglobin, total protein, blood IL-6, CRP; proportion of CD117+ and CD34+ mononuclear cells, CD14+ monocytes, CD14+ granulocytes, HLA-DR+ mononuclear cells, defensin + granulocytes.
On the day +8, patients from the main group, against the comparison group showed an increase in lymphocytes, monocytes, CD117+ and CD34+ cell counts. Serum IL-6 and CRP were decreased in both groups of the patients to a similar degree. Terms of hospitalization in the main group were 32.8 days, against 39.6 in comparison group. The number of complications per 1 case was, respectively, 21 versus 39, thus being 1.8 times less than in comparison group. When developing complications, anemia (Hb < 90 g/l), or hypoproteinaemia (< 60 g/l) in the main group was, respectively, 2.5and 3.5-fold less than in the comparison group.
Treatment with sodium deoxyribonucleate in polytrauma may promote migration of blood precursors to the bloodstream, increase anti-infectious properties of leukocytes, reduce duration of anemia and hypoproteinemia, number of complications and decrease the terms of hospitalization.
About the Authors
L. P. PivovarovaSt. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Pivovarova Ludmila Pavlovna - PhD, MD (Мedicine), Head, Department of Laboratory Diagnostics.
192242, St. Petersburg, Budapest str., 3. Phone: 7 (812) 384-46-68, Fax: 7 (812) 384-46-46
Competing Interests: no conflict of interest
M. I. Gromov
St. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Gromov Mikhail Ivanovich - PhD, MD (Мedicine), Head, Efferent Therapy Department.
St. PetersburgCompeting Interests: no conflict of interest
A. N. Tulupov
St. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Tulupov Aleksandr Nikolaevich - PhD, MD (Мedicine), Professor, Head, Combined Injury Department.
St. Petersburg
Competing Interests: no conflict of interest
V. N. Lapshin
St. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Lapshin Vladimir Nikolaevich - PhD, MD (Мedicine), Professor, Head, Anesthesiology and Resuscitation Department.
St. Petersburg
Competing Interests: no conflict of interest
I. V. Osipova
St. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Osipova Irina Viktorovna - PhD (Мedicine), Senior Research Associate, Department of Laboratory Diagnostics.
St. Petersburg
Competing Interests: no conflict of interest
O. B. Ariskina
St. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Ariskina Olga Borisovna - PhD (Biology), Research Associate, Department of Laboratory Diagnostics.
St. Petersburg
Competing Interests: no conflict of interest
A. V. Nikitin
St. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Nikitin Aleksandr Valeryevich - Сombined Тrauma Physician.
St. PetersburgCompeting Interests: no conflict of interest
M. E. Malyshev
St. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Malyshev Mikhail Evgenievich - PhD, МD (Biology), Head, City Laboratory of Immunogenetics and Serodiagnosis.
St. Petersburg
Competing Interests: no conflict of interest
E. V. Markelova
St. Petersburg I. Dzhanelidze Research Institute of Emergency
Russian Federation
Markelova Elena Valeryevna - Clinical Laboratory Diagnostics Doctor.
St. Petersburg
Competing Interests: no conflict of interest
References
1. Bagnenko S.F., Pivovarova L.P., Osipova I.V., Malyshev M.E., Ariskina O.B. The state of granulocytopoiesis in patients with severe sepsis that developed after combined mechanical trauma. Infektsii v khirurgii = Infections in Surgery, 2013, no. 1, pp. 44-48. (In Russ.)
2. Bagnenko S.F., Pivovarova L.P., Osipova I.V., Malyshev M.E., Ariskina O.B. Post-traumatic anemia in patients with severe mechanical injury. Skoraya meditsinskaya pomoshch = Emergency Medical Care, 2013, Vol. 14, no. 4, pp. 41-46. (In Russ.)
3. Besednova N.N., Zaporozhets T.S. The effect of prokaryotes deoxyribonucleic acid on humoral and cellular factors of innate and adaptive vertebrate immunity. Tikhookeanskiy meditsinskiy zhurnal = Pacific Medical Journal, 2009, no. 3, pp. 8-12. (In Russ.)
4. Budikhina A.S., Pinegin B.V. α-Defensins – antimicrobial peptides of neutrophils: properties and functions. Immunologiya = Immunology, 2008, no. 5, pp. 317-320. (In Russ.)
5. Gromov M.I., Pivovarova L.P. The use of the immunomodulator derinat in the treatment of surgical patients with severe sepsis. Fundamentalnyye issledovaniya = Fundamental Research, 2012, no. 7, pp. 289-295. (In Russ.)
6. Zemskov A.M., Zemskov V.M., Petrov A.V., Nikitin A.V. To the mechanism of stimulation of immunogenesis by sodium nucleinate. Immunologiya = Immunology, 1981, no. 1, pp. 52-55. (In Russ.)
7. Ivchenko D.R., Pivovarova L.P., Tulupov A.N. Immunoprophylaxis of post-traumatic pleural empyema. Skoraya meditsinskaya pomoshch = Emergency Medical Care, 2004, Vol. 5, no. 1, pp. 159-160. (In Russ.)
8. Kaplina E.N., Weinberg Yu.P. Derinat is a natural immunomodulator for children and adults. Ed. 3rd, fix and add.]. Moscow: Scientific Book, 2007. 240 p.
9. Kokryakov V.N., Kovalchuk L.V., Aleshina G.M., Shamova O.V. Cationic antimicrobial peptides as molecular factors of immunity:multifunctionality. Zhurnal mikrobiologii epidemiologii i immunologii = Journal of Microbiology Epidemiology and Immunology, 2006, no. 2, pp. 98-105. (In Russ.)
10. Lebedev V.F., Gavrilin S.V., Kirov M.Yu., Neymark M.I. , Levit A.L., Malkova O.G., Ostanin A.A., Chernykh E.R., Streltsova E.I., Kon E.M., Nikolenko A.V., Lebedev M.F., Chernyshkova M.V., Vashchenkov V.V., Rud A.A. The results of a multicenter prospective controlled study of the effectiveness of the drug recombinant human interleukin-2 (roncoleukin) in the complex intensive care of severe sepsis. Intensivnaya terapiya = Intensive Care, 2007, no. 3, pp. 20-31. (In Russ.)
11. Malyshev M.E., Sadulayev D.Sh., Ariskina O.B., Popenko L.N. Bacterial translocation into the systemic circulation in patients with combined trauma. Vestnik Avitsenny = Bulletin of Avicenna, 2012. Vol. 53, no. 4, pp. 53-56. (In Russ.)
12. Polovinkina V.S., Markov E.Yu. The structure and immunoadjuvant properties of CpG-DNA. Meditsinskaya immunologiya = Medical Immunology (Russia), 2010, Vol. 12, no. 6, pp. 469-476. (In Russ.) doi: 10.15789/1563-0625-2010-6-469-476.
13. Rusinova T.V. The mechanism of influence of nucleic acid preparations on the production of pro-inflammatory cytokines in vitro in the norm and in the infectious process. Sovremennyye problemy nauki i obrazovaniya = Modern Problems of Science and Education, 2016, no. 3, pp. 11-14. (In Russ.)
14. Seleznev S.A., Bagnenko S.F., Shapot Yu.B., Kurygin A.A. Traumatic disease and its complications]. St. Petersburg: Polytechnic, 2004. 414 p.
15. Filatov O.Yu., Kashaeva O.V., Bugrimov D.Yu., Klimovich A.A. Morphophysiological principles of the immunological action of eukaryotic DNA. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2013, Vol. 7 (16), no. 4, pp. 385-390. (In Russ.)
16. Tsibin Yu.N. A multivariate assessment of the severity of traumatic shock in a clinic. Vestnik khirurgii im. I.I. Grekova = Grekov’s Bulletin of Surgery, 1980, Vol. 125, no. 9, pp. 62-67. (In Russ.)
17. Baker S.P., O’Neill B. The injury severity score: update. J. Trauma, 1976, Vol. 16, no. 11, pp. 882-885.
18. Ballas Z.K. Modulation of NK cell activity by CpG oligodeoxynucleotides. Immunologic Research, 2007, Vol. 39, no. 1-3, pp. 15-21.
19. Edling C.E., Hallberg B. c-Kit – a hematopoietic cell essential receptor tyrosine kinase. Int. J. Biochem. Cell Biol., 2007, Vol. 39, no. 11, pp. 1995-1998.
20. Goerdt S., Orfanos C.E. Other functions, other genes: alternative activation of antigen-presenting cells. Immunity, 1999, no. 10, pp. 137-142.
21. Goldfarb Y., Levi B., Sorski L., Frenkel D., Ben-Eliyahu S. СpG-C immunotherapeutic efficacy is jeopardized by ongoing exposure to stress: Potential implications for clinical use. Brain Behav. Immun., 2011. Vol. 25, no. 1, pp. 67-76.
22. Lee M.L. Strand V. Intravenous immunoglobulins in clinical practice. Marcel Dekker. New York, Basel, Hong Kong, 1997. 509 p.
23. Liu J., Rybakina E.G., Korneva E.A. Noda M. Effects of Derinat on ischemia-reperfusion-induced pressure ulcer mouse model. J. Pharmacol. Sci., 2018, Vol. 138, no. 2, pp. 123-130.
24. Schetter C., Vollmer J. Toll-like receptors involved in the response to microbial pathogens: development of agonists for Toll-like receptor 9. Curr. Opin. Drug Discov. Dev., 2004, Vol. 7, no. 2, pp. 204-210.
25. Vollmer J., Krieg A.M. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv. Drug Deliv. Rev., 2009, Vol. 61, no. 3, pp. 195-204.
26. Vollmer J., Weeratna R.D., Jurk M., Samulowitz U., Mccluskie M.J., Payette P., Davis H.L., Schetter C., Krieg A.M. Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation. Immunology, 2004, Vol. 113, no. 2, pp. 212-223.
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21. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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24. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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25. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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26. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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28. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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29. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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30. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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31. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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33. ВЛИЯНИЕ ДЕЗОКСИРИБОНУКЛЕАТА НАТРИЯ НА ПРОТИВОИНФЕКЦИОННУЮ ЗАЩИТУ И КРОВЕТВОРЕНИЕ У ПОСТРАДАВШИХ С ПОЛИТРАВМОЙ (РАНДОМИЗИРОВАННОЕ ПРОСПЕКТИВНОЕ ДВОЙНОЕ СЛЕПОЕ ПЛАЦЕБО КОНТРОЛИРУЕМОЕ ИССЛЕДОВАНИЕ) | |
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For citations:
Pivovarova L.P., Gromov M.I., Tulupov A.N., Lapshin V.N., Osipova I.V., Ariskina O.B., Nikitin A.V., Malyshev M.E., Markelova E.V. Influence of sodium desoxyribonucleate on anti-infectious protection and hematopoiesis in patients with polytrauma (randomized prospective, double-blind, placebo-controlled study). Medical Immunology (Russia). 2020;22(4):729-740. (In Russ.) https://doi.org/10.15789/1563-0625-IOS-1923