3 research outputs found
ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΡΠ°ΡΠΈΠ»ΠΎΠΊΠΎΠΊΠΊΠΎΠ²ΠΎΠ³ΠΎ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³Π° ph20 ΠΈ Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³Π° ΡΠΈΠ½Π΅Π³Π½ΠΎΠΉΠ½ΠΎΠΉ ΠΏΠ°Π»ΠΎΡΠΊΠΈ ph57 ΠΏΡΠΈ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΡ ΠΈΠΌΠΏΡΠ΅Π³Π½Π°ΡΠΈΠΈ Π² ΠΎΡΡΠΎΠΏΠ΅Π΄ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ½ΡΠ΅ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ ΠΈΠ· ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°ΡΠ° (ΠΊΠΎΡΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΠΌΠ΅Π½ΡΠ°)
Background: The problem of bacterial colonization of implants used in medical practice continues to be relevant regardless of the material of the implant. Particular attention deserves polymeric implants, which are prepared ex tempore from polymethyl methacrylate, for example - duting orthopedic surgical interventions (so-called "bone cement"). The protection of such implants by antibiotic impregnation is subjected to multiple criticisms, therefore, as an alternative to antibiotics, lytic bacteriophages with a number of unique advantages can be used - however, no experimental studies have been published on the possibility of impregnating bacteriophages into polymethyl methacrylate and their antibacterial activity assessment under such conditions.Aims: to evaluate the possibility of physical placement of bacteriophages in polymethylmethacrylate and to characterize the lytic antibacterial effect of two different strains of bacteriophages when impregnated into polymer carrier ex tempore during the polymerization process in in vitro model.Materials and methods: Β First stage - Atomic force microscopy (AFM) of polymethyl methacrylate samples for medical purposes was used to determine the presence and size of caverns in polymethyl methacrylate after completion of its polymerization at various reaction Β temperatures (+6β¦+25Β°C and +18β¦+50Β°C).The second stage was performed in vitro and included an impregnation of two different bacteriophage strains (phage ph20 active against S. aureus and ph57 active against Ps. aeruginosa) into polymethyl methacrylate during the polymerization process, followed by determination of their antibacterial activity.Results: ACM showed the possibility of bacteriophages placement in the cavities of polymethyl methacrylate - the median of the section and the depth of cavities on the outer surface of the polymer sample polymerized at +18β¦+50Β°C were 100.0 and 40.0 nm, respectively, and on the surface of the transverse cleavage of the sample - 120.0 and 100.0 nm, respectively, which statistically did not differ from the geometric dimensions of the caverns of the sample polymerized at a temperature of +6β¦+25Β°C.The study of antibacterial activity showed that the ph20 bacteriophage impregnated in polymethyl methacrylate at +6β¦+25Β°C lost its effective titer within the first six days after the start of the experiment, while the phage ph57 retained an effective titer for at least 13 days.Conclusion: the study confirmed the possibility of bacteriophages impregnation into medical grade polymethyl methacrylate, maintaining the effective titer of the bacteriophage during phage emission into the external environment, which opens the way for the possible application of this method of bacteriophage delivery in clinical practice. It is also assumed that certain bacteriophages are susceptible to aggressive influences from the chemical components of "bone cement" and / or polymerization reaction products, which requires strict selection of bacteriophage strains that could be suitable for this method of delivery.ΠΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠ΅. ΠΡΠΎΠ±Π»Π΅ΠΌΠ° Π±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΊΠΎΠ»ΠΎΠ½ΠΈΠ·Π°ΡΠΈΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ
Β Π²Β ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅ ΠΈΠΌΠΏΠ»Π°Π½ΡΠ°ΡΠΎΠ² ΠΈΠ· ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»ΠΎΠ² ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠ°Π΅Ρ ΠΎΡΡΠ°Π²Π°ΡΡΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ, Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎ ΠΎΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π΄Π»Ρ ΠΈΡ
ΠΈΠ·Π³ΠΎΡΠΎΠ²Π»Π΅Π½ΠΈΡ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π°. ΠΡΠ΄Π΅Π»ΡΠ½ΠΎΠ³ΠΎ Π²Π½ΠΈΠΌΠ°Π½ΠΈΡ Π·Π°ΡΠ»ΡΠΆΠΈΠ²Π°ΡΡ ΠΈΠΌΠΏΠ»Π°Π½ΡΠΈΡΡΠ΅ΠΌΡΠ΅Β Π²Β ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ½ΡΠ΅ ΠΈΠΌΠΏΠ»Π°Π½ΡΠ°ΡΡ, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΈΠ·Π³ΠΎΡΠΎΠ²Π»ΡΡΡ exΒ tempore (ΠΏΠΎ ΠΌΠ΅ΡΠ΅ Π½Π°Π΄ΠΎΠ±Π½ΠΎΡΡΠΈ) ΠΈΠ· ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°ΡΠ°, Π½Π°ΠΏΡΠΈΠΌΠ΅Ρ ΠΏΡΠΈ ΠΎΡΡΠΎΠΏΠ΅Π΄ΠΈΡΠ΅ΡΠΊΠΈΡ
Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π²ΠΌΠ΅ΡΠ°ΡΠ΅Π»ΡΡΡΠ²Π°Ρ
(ΡΠ°ΠΊ Π½Π°Π·ΡΠ²Π°Π΅ΠΌΡΠΉ ΠΊΠΎΡΡΠ½ΡΠΉ ΡΠ΅ΠΌΠ΅Π½Ρ). ΠΠ°ΡΠΈΡΠ° ΡΠ°ΠΊΠΈΡ
ΠΈΠΌΠΏΠ»Π°Π½ΡΠ°ΡΠΎΠ² ΠΏΡΡΠ΅ΠΌ ΠΈΠΌΠΏΡΠ΅Π³Π½Π°ΡΠΈΠΈΒ Π²Β Π½ΠΈΡ
Π°Π½ΡΠΈΠ±ΠΈΠΎΡΠΈΠΊΠΎΠ² ΠΏΠΎΠ΄Π²Π΅ΡΠ³Π°Π΅ΡΡΡ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΊΡΠΈΡΠΈΠΊΠ΅, ΠΏΠΎΡΡΠΎΠΌΡΒ Π²Β ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ Π°Π»ΡΡΠ΅ΡΠ½Π°ΡΠΈΠ²Ρ Π°Π½ΡΠΈΠ±ΠΈΠΎΡΠΈΠΊΠ°ΠΌ ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Ρ Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΈ, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΠ΅ ΡΡΠ΄ΠΎΠΌ ΡΠ½ΠΈΠΊΠ°Π»ΡΠ½ΡΡ
ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ², ΠΎΠ΄Π½Π°ΠΊΠΎ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ
ΡΠ°Π±ΠΎΡ ΠΏΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΈΠΌΠΏΡΠ΅Π³Π½Π°ΡΠΈΠΈ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ²Β Π²Β ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°ΡΒ ΠΈΒ Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈΒ Π²Β ΡΠ°ΠΊΠΈΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
Β Π²Β Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ΅ Π½Π΅ ΠΎΠΏΡΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½ΠΎ.Β Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΒ β ΠΈΠ·ΡΡΠΈΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠΈΠ·ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ°Π·ΠΌΠ΅ΡΠ΅Π½ΠΈΡ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ²Β Π²Β ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°ΡΠ΅Β ΠΈ Π²Β ΠΌΠΎΠ΄Π΅Π»ΠΈΒ inΒ vitroΒ ΠΎΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°ΡΡ Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΠΉ ΡΡΡΠ΅ΠΊΡ Π΄Π²ΡΡ
ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΡΠ°ΠΌΠΌΠΎΠ² Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ² ΠΏΡΠΈ ΠΈΡ
ΠΈΠΌΠΏΡΠ΅Π³Π½Π°ΡΠΈΠΈΒ Π²Β ΠΈΠ·Π³ΠΎΡΠ°Π²Π»ΠΈΠ²Π°Π΅ΠΌΡΠΉ exΒ tempore ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠ½ΡΠΉ Π½ΠΎΡΠΈΡΠ΅Π»Ρ Π½Π° ΡΡΠ°ΠΏΠ΅ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ·Π°ΡΠΈΠΈ.Β ΠΠ΅ΡΠΎΠ΄Ρ. ΠΠ΅ΡΠ²ΡΠΌ ΡΡΠ°ΠΏΠΎΠΌ Π±ΡΠ»Π° ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π°Β Π°ΡΠΎΠΌΠ½ΠΎ-ΡΠΈΠ»ΠΎΠ²Π°Ρ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΡ (ΠΠ‘Π) ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°ΡΠ° ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠ³ΠΎ Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΡ Π΄Π»Ρ Π²ΡΡΡΠ½Π΅Π½ΠΈΡ Π½Π°Π»ΠΈΡΠΈΡΒ ΠΈΒ ΡΠ°Π·ΠΌΠ΅ΡΠΎΠ² ΠΊΠ°Π²Π΅ΡΠ½, ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π²ΡΠΈΡ
ΡΡ ΠΏΠΎΡΠ»Π΅ Π·Π°Π²Π΅ΡΡΠ΅Π½ΠΈΡ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ·Π°ΡΠΈΠΈ ΠΏΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΠΎΠΌ Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡ ΡΠ΅Π°ΠΊΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠΌΠ΅ΡΠΈ (+6β¦+25 Β°CΒ ΠΈΒ +18β¦+50 Β°C). ΠΡΠΎΡΡΠΌ ΡΡΠ°ΠΏΠΎΠΌ inΒ vitro Π±ΡΠ»ΠΎ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΠΈΠΌΠΏΡΠ΅Π³Π½Π°ΡΠΈΡ Π΄Π²ΡΡ
ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΡΡΠ°ΠΌΠΌΠΎΠ² Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ² (ph20, Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎΒ Π²Β ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ StaphylococcusΒ aureus,Β ΠΈΒ ph57, Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎΒ Π²Β ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΈ PseudomonasΒ aeruginosa)Β Π²Β ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°Ρ Π½Π° ΡΡΠ°ΠΏΠ΅ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ·Π°ΡΠΈΠΈΒ ΡΒ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠΈΠΌ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ΠΌ ΠΈΡ
Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ.Β Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ.Β ΠΒ Ρ
ΠΎΠ΄Π΅ Π²ΡΠΏΠΎΠ»Π½Π΅Π½ΠΈΡ ΠΠ‘Π ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠ°Π·ΠΌΠ΅ΡΠ΅Π½ΠΈΡ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ²Β Π²Β ΠΊΠ°Π²Π΅ΡΠ½Π°Ρ
ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°ΡΠ°: ΠΌΠ΅Π΄ΠΈΠ°Π½Π° ΡΠ΅ΡΠ΅Π½ΠΈΡΒ ΠΈΒ Π³Π»ΡΠ±ΠΈΠ½Ρ ΠΊΠ°Π²Π΅ΡΠ½ Π½Π° Π²Π½Π΅ΡΠ½Π΅ΠΉ ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠΈ ΠΎΠ±ΡΠ°Π·ΡΠ°, ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠΈ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ΅ +18β¦+50 Β°C, ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 100,0Β ΠΈΒ 40,0Β Π½ΠΌ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ,Β Π°Β Π½Π° ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠΈ ΠΏΠΎΠΏΠ΅ΡΠ΅ΡΠ½ΠΎΠ³ΠΎ ΡΠΊΠΎΠ»Π° ΠΎΠ±ΡΠ°Π·ΡΠ°Β β 120,0Β ΠΈΒ 100,0Β Π½ΠΌ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ, ΡΡΠΎ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π½Π΅ ΠΎΡΠ»ΠΈΡΠ°Π»ΠΎΡΡ ΠΎΡ Π³Π΅ΠΎΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ°Π·ΠΌΠ΅ΡΠΎΠ² ΠΊΠ°Π²Π΅ΡΠ½ ΠΎΠ±ΡΠ°Π·ΡΠ°, ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ·ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠΈ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ΅ +6β¦+25 Β°C. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΎ, ΡΡΠΎ ΠΈΠΌΠΏΡΠ΅Π³Π½ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ ΠΏΡΠΈ +6β¦+25 Β°CΒ Π²Β ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°Ρ ΡΡΠ°ΡΠΈΠ»ΠΎΠΊΠΎΠΊΠΊΠΎΠ²ΡΠΉ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³Β ph20 ΡΡΡΠ°ΡΠΈΠ» ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΉ ΡΠΈΡΡ ΡΠΆΠ΅Β Π²Β ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΏΠ΅ΡΠ²ΡΡ
ΡΠ΅ΡΡΠΈ ΡΡΡΠΎΠΊΒ ΡΒ ΠΌΠΎΠΌΠ΅Π½ΡΠ° Π½Π°ΡΠ°Π»Π° ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°, ΡΠΎΠ³Π΄Π° ΠΊΠ°ΠΊ ΡΠΈΠ½Π΅Π³Π½ΠΎΠΉΠ½ΡΠΉ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³Β ph57 ΡΠΎΡ
ΡΠ°Π½ΡΠ» ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΉ ΡΠΈΡΡ ΠΊΠ°ΠΊ ΠΌΠΈΠ½ΠΈΠΌΡΠΌΒ Π²Β ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 13Β ΡΡΡ.Β ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅.Β ΠΒ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ Π±ΡΠ»Π° ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΈΠΌΠΏΡΠ΅Π³Π½Π°ΡΠΈΠΈ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ²Β Π²Β ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ»ΠΌΠ΅ΡΠ°ΠΊΡΠΈΠ»Π°Ρ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠ³ΠΎ Π½Π°Π·Π½Π°ΡΠ΅Π½ΠΈΡΒ ΡΒ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ΠΌ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΠΈΡΡΠ° Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³Π° ΠΏΡΠΈ Π΅Π³ΠΎ ΡΠΌΠΈΡΡΠΈΠΈ Π²ΠΎ Π²Π½Π΅ΡΠ½ΡΡ ΡΡΠ΅Π΄Ρ, ΡΡΠΎ ΠΎΡΠΊΡΡΠ²Π°Π΅Ρ ΠΏΡΡΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠ°ΠΊΠΎΠ³ΠΎ ΡΠΏΠΎΡΠΎΠ±Π° Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ²Β Π²Β ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅. Π’Π°ΠΊΠΆΠ΅ ΡΠ΄Π΅Π»Π°Π½Ρ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡΒ ΠΎΒ Π²Π΅ΡΠΎΡΡΠ½ΠΎΠΉ ΠΏΠΎΠ΄Π²Π΅ΡΠΆΠ΅Π½Π½ΠΎΡΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ² Π°Π³ΡΠ΅ΡΡΠΈΠ²Π½ΡΠΌ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡΠΌ ΡΠΎ ΡΡΠΎΡΠΎΠ½Ρ Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² Β«ΠΊΠΎΡΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΠΌΠ΅Π½ΡΠ°Β» ΠΈ/ΠΈΠ»ΠΈ ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ² ΡΠ΅Π°ΠΊΡΠΈΠΈ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΈΠ·Π°ΡΠΈΠΈ, ΡΡΠΎ ΡΡΠ΅Π±ΡΠ΅Ρ ΡΡΡΠΎΠ³ΠΎΠ³ΠΎ ΠΎΡΠ±ΠΎΡΠ° ΠΏΡΠΈΠ³ΠΎΠ΄Π½ΡΡ
Π΄Π»Ρ ΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠ³ΠΎ ΡΠΏΠΎΡΠΎΠ±Π° Π΄ΠΎΡΡΠ°Π²ΠΊΠΈ ΡΡΠ°ΠΌΠΌΠΎΠ² Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³ΠΎΠ²
Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations
Immature hematopoietic progenitors are a constant source for renewal of hemocyte populations and the basic component of the tissue and cell repair apparatus. A unique property of these cells of internalizing extracellular double-stranded DNA has been previously shown. The leukostimulatory effect demonstrated in our pioneering studies was considered to be due to the feature of this cell. In the present research, we have analyzed the effects of DNA genome reconstructor preparation (DNAgr), DNAmix, and human recombinant angiogenin on both hematopoietic stem cells and multipotent progenitors. Treatment with bone marrow cells of experimental mice with these preparations stimulates colony formation by hematopoietic stem cells and proliferation of multipotent descendants. The main lineage responsible for this is the granulocyte-macrophage hematopoietic lineage. Using fluorescent microscopy as well as FACS assay, co-localization of primitive c-Kit- and Sca-1-positive progenitors and the TAMRA-labeled double-stranded DNA has been shown. Human recombinant angiogenin was used as a reference agent. Cells with specific markers were quantified in intact bone marrow and colonies grown in the presence of inducers. Quantitative analysis revealed that a total of 14,000 fragment copies of 500 bp, which is 0.2% of the haploid genome, can be delivered into early progenitors. Extracellular double-stranded DNA fragments stimulated the colony formation in early hematopoietic progenitors from the bone marrow, which assumed their effect on cells in G0. The observed number of Sca1+/c-Kit+ cells in colonies testifies to the possibility of both symmetrical and asymmetrical division of the initial hematopoietic stem cell and its progeny
ΠΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΡΠ΅ ΠΈ ΠΏΡΠΎΡΠ΅ΠΊΡΠΈΠ²ΡΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΊΠ°Π½Π΄ΠΈΠ΄Π°ΡΠ½ΠΎΠΉ ΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΠΎΠΉ Π²Π°ΠΊΡΠΈΠ½Ρ ΠΏΡΠΎΡΠΈΠ² SARS-CoV-2
Background. In 2020, the pandemic caused by novel coronavirus infection has become one of the most critical global health challenges during the past century. The lack of a vaccine, as the most effective way to control the novel infection, has prompted the development of a large number of preventive products by the scientific community. We have developed a candidate vaccine (EpiVacCorona) against novel coronavirus infection caused by SARS-CoV-2 that is based on chemically synthesized peptides conjugated to a carrier protein and adsorbed on aluminum hydroxide and studied the specific activity of the developed vaccine.
Aims study of the immunogenicity and protectivity of the peptide candidate vaccine EpiVacCorona.
Methods. The work was performed using standard molecular biological, virological and histological methods.
Results. It was demonstrated that EpiVacCorona, when administered twice, spaced 14 days apart, to hamsters, ferrets, and non-human primates (african green monkeys, rhesus macaques) at a dose of 260 g, which is equal to one inoculation dose for humans, induces virus-specific antibodies in 100% of the animals. Experiments in hamsters showed this vaccine to be associated with the dose-dependent immunogenicity. The vaccine was shown to accelerate the elimination of the virus from the upper respiratory tract in ferrets and prevent the development of pneumonia in hamsters and non-human primates following a respiratory challenge with novel coronavirus.
Conclusions. The results of a preclinical specific activity study indicate that the use of EpiVacCorona has the potential for human vaccination.ΠΠ±ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠ΅. Π 2020 Π³. ΠΏΠ°Π½Π΄Π΅ΠΌΠΈΡ, Π²ΡΠ·Π²Π°Π½Π½Π°Ρ Π½ΠΎΠ²ΠΎΠΉ ΠΊΠΎΡΠΎΠ½Π°Π²ΠΈΡΡΡΠ½ΠΎΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠ΅ΠΉ, ΡΡΠ°Π»Π° ΠΎΠ΄Π½ΠΈΠΌ ΠΈΠ· ΡΠ°ΠΌΡΡ
ΡΠ΅ΡΡΠ΅Π·Π½ΡΡ
ΠΈΡΠΏΡΡΠ°Π½ΠΈΠΉ Π΄Π»Ρ Π³Π»ΠΎΠ±Π°Π»ΡΠ½ΠΎΠ³ΠΎ Π·Π΄ΡΠ°Π²ΠΎΠΎΡ
ΡΠ°Π½Π΅Π½ΠΈΡ Π·Π° ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π΅ ΡΡΠΎΠ»Π΅ΡΠΈΠ΅. ΠΡΡΡΡΡΡΠ²ΠΈΠ΅ Π²Π°ΠΊΡΠΈΠ½Ρ ΠΊΠ°ΠΊ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π΄Π΅ΠΉΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΡΠΏΠΎΡΠΎΠ±Π° Π±ΠΎΡΡΠ±Ρ ΠΏΡΠΎΡΠΈΠ² Π½ΠΎΠ²ΠΎΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΈ ΠΎΠ±ΡΡΠ»ΠΎΠ²ΠΈΠ»ΠΎ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΡ Π½Π°ΡΡΠ½ΡΠΌ ΡΠΎΠΎΠ±ΡΠ΅ΡΡΠ²ΠΎΠΌ Π±ΠΎΠ»ΡΡΠΎΠ³ΠΎ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ². ΠΠ°ΠΌΠΈ Π±ΡΠ»Π° ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π° ΠΊΠ°Π½Π΄ΠΈΠ΄Π°ΡΠ½Π°Ρ Π²Π°ΠΊΡΠΈΠ½Π° (ΠΠΏΠΈΠΠ°ΠΊΠΠΎΡΠΎΠ½Π°) ΠΏΡΠΎΡΠΈΠ² Π½ΠΎΠ²ΠΎΠΉ ΠΊΠΎΡΠΎΠ½Π°Π²ΠΈΡΡΡΠ½ΠΎΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΈ SARS-CoV-2 Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈ ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΏΠ΅ΠΏΡΠΈΠ΄ΠΎΠ², ΠΊΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π½Π° Π±Π΅Π»ΠΎΠΊ-Π½ΠΎΡΠΈΡΠ΅Π»Ρ ΠΈ Π°Π΄ΡΠΎΡΠ±ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π½Π° Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈΠ΄ Π°Π»ΡΠΌΠΈΠ½ΠΈΡ, ΠΈ ΠΈΠ·ΡΡΠ΅Π½Π° Π΅Π΅ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ.
Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΡΡ
ΠΈ ΠΏΡΠΎΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΡΠ²ΠΎΠΉΡΡΠ² ΠΊΠ°Π½Π΄ΠΈΠ΄Π°ΡΠ½ΠΎΠΉ ΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΠΎΠΉ Π²Π°ΠΊΡΠΈΠ½Ρ ΠΠΏΠΈΠΠ°ΠΊΠΠΎΡΠΎΠ½Π°.
ΠΠ΅ΡΠΎΠ΄Ρ. Π Π°Π±ΠΎΡΠ° Π±ΡΠ»Π° Π²ΡΠΏΠΎΠ»Π½Π΅Π½Π° ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
, Π²ΠΈΡΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ Π³ΠΈΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ².
Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΠΠΏΠΈΠΠ°ΠΊΠΠΎΡΠΎΠ½Π° ΠΏΡΠΈ Π΄Π²ΡΠΊΡΠ°ΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Ρ ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»ΠΎΠΌ Π² 14 Π΄Π½Π΅ΠΉ Ρ
ΠΎΠΌΡΠΊΠ°ΠΌ, Ρ
ΠΎΡΡΠΊΠ°ΠΌ ΠΈ Π½ΠΈΠ·ΡΠΈΠΌ ΠΏΡΠΈΠΌΠ°ΡΠ°ΠΌ (Π°ΡΡΠΈΠΊΠ°Π½ΡΠΊΠΈΠΌ Π·Π΅Π»Π΅Π½ΡΠΌ ΠΌΠ°ΡΡΡΡΠΊΠ°ΠΌ, ΠΌΠ°ΠΊΠ°ΠΊΠ°ΠΌ-ΡΠ΅Π·ΡΡΠ°ΠΌ) Π² Π΄ΠΎΠ·Π΅ 260 ΠΌΠΊΠ³, ΡΠ°Π²Π½ΠΎΠΉ ΠΎΠ΄Π½ΠΎΠΉ ΠΏΡΠΈΠ²ΠΈΠ²ΠΎΡΠ½ΠΎΠΉ Π΄ΠΎΠ·Π΅ Π΄Π»Ρ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°, Π²ΡΠ·ΡΠ²Π°Π΅Ρ ΠΈΠ½Π΄ΡΠΊΡΠΈΡ Π²ΠΈΡΡΡΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π°Π½ΡΠΈΡΠ΅Π» Ρ 100% ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
. Π ΠΎΠΏΡΡΠ°Ρ
Π½Π° Ρ
ΠΎΠΌΡΠΊΠ°Ρ
ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π²Π°ΠΊΡΠΈΠ½Π½ΡΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ Π΄ΠΎΠ·ΠΎΠ·Π°Π²ΠΈΡΠΈΠΌΠΎΠΉ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΡΡ, Π²Π°ΠΊΡΠΈΠ½Π° ΠΈΠ½Π΄ΡΡΠΈΡΡΠ΅Ρ ΡΡΠΊΠΎΡΠ΅Π½ΠΈΠ΅ ΡΠ»ΠΈΠΌΠΈΠ½Π°ΡΠΈΠΈ Π²ΠΈΡΡΡΠ° ΠΈΠ· Π²Π΅ΡΡ
Π½ΠΈΡ
Π΄ΡΡ
Π°ΡΠ΅Π»ΡΠ½ΡΡ
ΠΏΡΡΠ΅ΠΉ Ρ Ρ
ΠΎΡΡΠΊΠΎΠ² ΠΈ ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ°Π΅Ρ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΠΈΠΈ Ρ Ρ
ΠΎΠΌΡΠΊΠΎΠ² ΠΈ Π½ΠΈΠ·ΡΠΈΡ
ΠΏΡΠΈΠΌΠ°ΡΠΎΠ² ΠΏΠΎΡΠ»Π΅ ΡΠ΅ΡΠΏΠΈΡΠ°ΡΠΎΡΠ½ΠΎΠ³ΠΎ Π·Π°ΡΠ°ΠΆΠ΅Π½ΠΈΡ Π½ΠΎΠ²ΡΠΌ ΠΊΠΎΡΠΎΠ½Π°Π²ΠΈΡΡΡΠΎΠΌ.
ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΠΠΏΠΈΠΠ°ΠΊΠΠΎΡΠΎΠ½Π° Π΄Π»Ρ Π²Π°ΠΊΡΠΈΠ½Π°ΡΠΈΠΈ Π»ΡΠ΄Π΅ΠΉ