Correction of bone marrow failure in patients with polytrauma by injection of native DNA fragments (randomized prospective double-blind placebo-controlled study)

Volume 6, Issue 3, June 2021     |     PP. 242-259      |     PDF (361 K)    |     Pub. Date: June 8, 2021
DOI: 10.54647/cm32508    95 Downloads     5163 Views  

Author(s)

Ludmila Pavlovna Pivovarova, Laboratory Diagnostics Department, Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Saint-Petersburg, Russia
Mikhail Ivanovich Gromov, Department of Efferent Therapy, Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Saint-Petersburg, Russia
Aleksandr Nikolaevich Tulupov, Department of Concomitant Injury, Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Saint-Petersburg, Russia
Vladimir Nikolaevich Lapshin, Department of Anesthesiology and Reanimatology, Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Saint-Petersburg, Russia
Aleksandr Valeryevich Nikitin, Department of Concomitant Injury, Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Saint-Petersburg, Russia
Irina Viktorovna Osipova, Laboratory Diagnostics Department, Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Saint-Petersburg, Russia
Olga Borisovna Ariskina, Laboratory Diagnostics Department, Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, Saint-Petersburg, Russia

Abstract
A single-center efficacy study of sodium deoxyribonucleate in 54 patients with polytrauma was conducted. The main/control group consisted of 27/27 patients (21/20 males), aged 39(29;51)/40(26;53) years with the Injury Severity Score of 26(22;34)/25(20;29). Sodium deoxyribonucleate is hydrophilic fragments of native DNA. Randomization: the patients as-signed with even numbers were given the study drug of an even batch, those assigned with odd numbers received the drug of an odd batch. Every vial in one batch contained 75 mg sodium deoxyribonucleate, vials of the other batch contained only a solvent. Intramuscular injections were given daily for 10 days starting from the post-injury day. Blood tests assessing red and main population of white cells, CD117+ and CD34+mononuclears, CD14+monocytes and CD14+granulocytes, HLA-DR+ mononuclears, defensin+ neutrophilic granulocytes (NG), IL-6, CRP were made before first injection, on post-injury Days 8 and 15. Hb and TP were regularly assessed. On post-injury Day 8 counts (^109/L) of lymphocytes (2.36±0.19/1.83±0.18; р=0.048), monocytes (0.89±0.007/0.69±0.007; р=0.049), CD117+ (0.81±0.07/0.44±0.07; р=0.000) and CD34+mononuclears (0.83±0.07/0.65±0.05; р=0.042) increased in patients of the main group as compared to the controls. On post-injury Day 15 the achieved monocyte count increase retained (0.65±0.07/0.46±0.05; р=0.033), while counts of CD14+monocytes (0.38±0.03/0.24±0.02; р=0.041), HLA-DR+ mononuclears (1.34±0.12/1.04±0.08; р=0.044) and defensin+NG (42.0%±2.4%/ 34.3%±3.7%; р=0.044) increased in patients of the main group as compared to the control one. In both groups the concentrations of IL-6, pg/mL (Day 1 - 115±14/134±14; р=0.343; Day 8 - 51±7/74±9; р=0.049; Day 15 - 25±3/29±5; р=0.496) and СRP, mg/L (Day 1 - 69±6/84±8; р=0.141; Day 8 - 82±13/82±12; р=1.000; Day 15 - 21±4/35±7; р=0.090) equally decreased. The study drug had a positive effect in reducing a hospital stay from 39.6 to 32.8 days, decreasing the number of complications in 1.8 times, and the duration of anemia and hypoproteinemia in 2.5 and 2.4 times respectively.

Keywords
polytrauma, bone marrow failure, hematopoiesis, hypoproteinemia, anemia, complications, sodium deoxyribonucleate

Cite this paper
Ludmila Pavlovna Pivovarova, Mikhail Ivanovich Gromov, Aleksandr Nikolaevich Tulupov, Vladimir Nikolaevich Lapshin, Aleksandr Valeryevich Nikitin, Irina Viktorovna Osipova, Olga Borisovna Ariskina, Correction of bone marrow failure in patients with polytrauma by injection of native DNA fragments (randomized prospective double-blind placebo-controlled study) , SCIREA Journal of Clinical Medicine. Volume 6, Issue 3, June 2021 | PP. 242-259. 10.54647/cm32508

References

[ 1 ] Tulupov A.N. Severe concomitant injury. [Tyazhelaya sochetannaya travma]. Saint-Petersburg: OOO «RA «Russkiy Yuvelir», 2015. [Rus]
[ 2 ] Kaplina E. N., Vaynberg Yu. P. Derinat is a natural immunomodulator for children and adults. 3rd ed., rev. and corr. [Derinat - prirodnyy immunomodulyator dlya detey i vzroslykh. 3-ye izd., per. i ispr.]. M.: “Nauchnaya kniga”, 2007. [Rus].
[ 3 ] Gromov M. I., Pivovarova L. P. Use of immunomodulator derinat in treatment of surgical patients with severe sepsis. Fundamental research, 2012; 7 (2): 289-295. [Rus]. URL: http://www.fundamental-research.ru/ru/article/view?id=30127 Epub 2020 Dec 17
[ 4 ] 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. https://www.sciencedirect.com/science/article/pii/S0169409X09000039?via%3Dihub
[ 5 ] Filatov O.Yu., Kashaeva O.V., Bugrimov D.Yu., Klimovich A.A. Morphophysiological principles of the immunological action of eukaryotic DNA. Russian Immunological Journal, 2013; 16(4): 385-390. [Rus]. elibrary.ru/download/elibrary_22390937_46334206.pdf
[ 6 ] Liu J., Rybakina E.G., Korneva E.A., Noda M. Effects of Derinat on ischemia-reperfusion-induced pressure ulcer mouse model. Journal of Pharmacological Sciences, 2018; 138(2): 123-130. https://www.sciencedirect.com/science/article/pii/S1347861318301804?via%3Dihub
[ 7 ] Baker S.P., O’Neill B., Haddon W., Long W.B. The Injury Severity Score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma, 1974; 14(3): 187-196. https://journals.lww.com/jtrauma/Citation/1976/11000/THE_INJURY_SEVERITY_SCORE__AN_UPDATE.6.aspx
[ 8 ] Tsybin Yu.N. A multivariate assessment of the severity of traumatic shock in a clinic. Grekov’s Bulletin of Surgery, 1980; 125(9): 62-67.
[ 9 ] Ganz T. Defensins: Antimicrobial peptides of innate immunity. Immunology, 2003; 3(9): 710-72. doi: 10.1038/nri1180
[ 10 ] Sechet E., Telford E.,  Bonamy C., Sansonetti Ph.J., Sperandio B. Natural molecules induce and synergize to boost expression of the human antimicrobial peptide β-defensin-3. PNAS, 2018; 115(42): E9869-E9878. doi: 10.1073/pnas.1805298115
[ 11 ] Edling C.E., Hallberg B. C-Kit- a hematopoietic cell essential receptor tyrosine kinase. Int J Biochem Cell Biol, 2007; 39: 1995-1998. https://www.sciencedirect.com/science/article/pii/S1357272507000167?via%3Dihub
[ 12 ] Maillard L., Sanfilippo S., Domenech C., Kasmi N., Petit L., Jacques S., Delezoide A., Guimiot F., Eladak S., Moison D., Nicolas N., Rouiller-Fabre V., Pozzi-Godin S., Mennesson B., Brival M., Letourneur F., Jaffredo T., Chomienne C., Souyri M. CD117hi expression identifies a human fetal hematopoietic stem cell population with high proliferation and self-renewal potential. Haematologica, 2020; 105(2): e43–e47. doi: 10.3324/haematol.2018.207811
[ 13 ] Malyshev ME, Pivovarova LP, Ariskina OB, Osipova IV. Post-traumatic anemia in patients with severe mechanical injury. Emergency Medical Aid, 2013; 14(4): 41-47. [Rus]. https://www.elibrary.ru/download/elibrary_18792944_50127236.pdf
[ 14 ] Bell E., Curry E.W., Megchelenbrink W., Jouneau L., Brochard V.,  Tomaz R.A.,  Mau K.H.T.,  Atlasi Y., de Souza R.A.,  Marks H.,  Stunnenberg H.G.,  Jouneau A., Azuara V.  Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency. Nat Commun, 2020;11(1):1112. doi: 10.1038/s41467-020-14916-7.
[ 15 ] Hanagata N. CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies Int J Nanomedicine, 2017; 12: 515-531. doi: 10.2147/IJN.S114477
[ 16 ] Polovinkina V.S., Markov E.Yu. The structure and immunoadjuvant properties of CpG-DNA. Medical Immunology, 2010; 12(6): 469-476. [Rus]. https://www.elibrary.ru/download/elibrary_15285474_53358590.pdf
[ 17 ] Goerdt S. Orfanos C.E. Other functions, other genes: alternative activation of antigen-presenting cells. Immunity, 1999; (10): 137–142. https://www.sciencedirect.com/science/article/pii/S107476130080014X?via%3Dihub
[ 18 ] Ballas Z.K. Modulation of NK cell activity by CpG oligodeoxynucleotides. Immunologic Research, 2007; 39(1–3): 15–21. https://www.ncbi.nlm.nih.gov/pubmed/17917052
[ 19 ] 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. Modern problems of science and education, 2016; (3): 11-14. [Rus]. https://www.science-education.ru/ru/article/view?id=24465