10 research outputs found
Π ΠΎΠ»Ρ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΡ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΡΠΈΡΡΠ΅ΠΌΡ ΡΠΈΠ±ΡΠΈΠ½ΠΎΠ»ΠΈΠ·Π° Π² ΠΎΡΠ΅Π½ΠΊΠ΅ ΡΡΠΆΠ΅ΡΡΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΠΌΠ°Π»ΡΡ ΡΠΎΡΡΠ΄ΠΎΠ² Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°
Background: Small vessel disease (SVD) is a common brain disease causing about 40% of all dementias and about 25% of ischemic strokes, which makes important the study of its pathophysiology and the search for its biomarkers. A number of studies have shown a significant role of endothelial dysfunction and nonspecific inflammation, as well as of some individual parameters of hemostasis disorders in the development of SVD.
Aim: To identify the role of the laboratory markers of fibrinolytic system in the assessment of the severity of white matter lesions in patients with SVD.
Materials and methods: This single center cross-sectional non-controlled observational study included 117 patients with dyscirculatory encephalopathy (chronic brain ischemia), with a mean ( SD) age of 57.7 11.5 years. Laboratory tests of the fibrinolytic system, endothelial dysfunction, markers of inflammation and for an integral assessment of plasma hemostasis were performed in all patients, including XIIa-dependent fibrinolysis, levels of plasminogen, alpha2-antiplasmin, plasminogen activator inhibitor 1 (PAI-1), fibrinogen, von Willebrand factor (vWF) and activity of blood coagulation factor VIII (FVIII), highly sensitive C-reactive protein and parameters of the thrombodynamics assay. In all the patients, brain magnetic resonance imaging was performed with the assessment of the white matter lesions by the Fazecas scale.
Results: Depending on the identified neuroimaging SVD markers (assessed with the Fazecas scale), the patients were divided into the SVD group (n = 54) and no-SVD group (n = 63). Those with SVD were older than those without (65 9 vs 51 10 years; p 0.001), had higher prevalence of arterial hypertension (p 0.001), diabetes mellitus (p = 0.029) and past thrombotic events (p 0.001). The SVD patients, compared to those without SVD, had a higher time of XIIa-dependent fibrinolysis (7.6 2.9 vs 6.5 1.7 min, p = 0.032), higher alpha2-antiplasmin levels (111 [95117] vs 105 [95111]%, p = 0.016) and higher clot density (D) (22789 [2056726411] vs 20627 [1832422650] U, p 0.001), although the parameters were within the reference ranges. As far as the thrombodynamics is concerned, the SVD group had higher values for all test parameters, as well as higher levels of the inflammation and endothelial dysfunction markers. Increased time of XIIa-dependent fibrinolysis was associated with higher probability of periventricular and subcortical leukoareosis grade 2 by the Fazecas scale (odds ratio 1.31 [1.071.60], p = 0.009), including an increase in the size and number of gliosis areas. Higher plasminogen levels were associated with a lower probability of leukoareosis by the Fazecas scale (odds ratio 0.97 [0.950.98], p 0.001).
Conclusion: The severity of fibrinolytic and hemostatic abnormalities correlates with the severity of brain SVD, thus forming the hypofibrinolytic and prothrombotic status of the patients with this disorder.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ. ΠΠΎΠ»Π΅Π·Π½Ρ ΠΌΠ°Π»ΡΡ
ΡΠΎΡΡΠ΄ΠΎΠ² (ΠΠΠ‘) ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°, Π²ΡΠ·ΡΠ²Π°ΡΡΠ΅Π΅ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΎΠΊΠΎΠ»ΠΎ 40% Π²ΡΠ΅Ρ
Π΄Π΅ΠΌΠ΅Π½ΡΠΈΠΉ ΠΈ 25% ΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΠ½ΡΡΠ»ΡΡΠΎΠ², ΡΡΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅Ρ Π²Π°ΠΆΠ½ΠΎΡΡΡ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π° ΠΈ ΠΏΠΎΠΈΡΠΊΠ° Π±ΠΈΠΎΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ². Π ΡΡΠ΄Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎΠΊΠ°Π·Π°Π½Π° Π²Π°ΠΆΠ½Π°Ρ ΡΠΎΠ»Ρ ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΠΈ ΠΈ Π½Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π²ΠΎΡΠΏΠ°Π»Π΅Π½ΠΈΡ, Π° ΡΠ°ΠΊΠΆΠ΅ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΠΎΡΠ΄Π΅Π»ΡΠ½ΡΡ
ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΎΠ² Π½Π°ΡΡΡΠ΅Π½ΠΈΡ Π³Π΅ΠΌΠΎΡΡΠ°Π·Π° Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΠΠΠ‘.
Π¦Π΅Π»Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ ΡΠΎΠ»Ρ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΡΠΈΡΡΠ΅ΠΌΡ ΡΠΈΠ±ΡΠΈΠ½ΠΎΠ»ΠΈΠ·Π° Π² ΠΎΡΠ΅Π½ΠΊΠ΅ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΡΡΠΈ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΡ Π±Π΅Π»ΠΎΠ³ΠΎ Π²Π΅ΡΠ΅ΡΡΠ²Π° Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠ‘.
ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π ΡΠ°ΠΌΠΊΠ°Ρ
ΠΎΠ΄Π½ΠΎΡΠ΅Π½ΡΡΠΎΠ²ΠΎΠ³ΠΎ ΠΏΠΎΠΏΠ΅ΡΠ΅ΡΠ½ΠΎΠ³ΠΎ Π½Π΅ΠΊΠΎΠ½ΡΡΠΎΠ»ΠΈΡΡΠ΅ΠΌΠΎΠ³ΠΎ ΠΎΠ±ΡΠ΅ΡΠ²Π°ΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Ρ 117 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π΄ΠΈΡΡΠΈΡΠΊΡΠ»ΡΡΠΎΡΠ½ΠΎΠΉ ΡΠ½ΡΠ΅ΡΠ°Π»ΠΎΠΏΠ°ΡΠΈΠ΅ΠΉ (Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΈΡΠ΅ΠΌΠΈΡ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°) Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ 57,7 11,5 Π³ΠΎΠ΄Π°. ΠΡΠ΅ΠΌ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°ΠΌ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Ρ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎ ΠΎΡΠ΅Π½ΠΊΠ΅ ΡΠΈΡΡΠ΅ΠΌΡ ΡΠΈΠ±ΡΠΈΠ½ΠΎΠ»ΠΈΠ·Π°, Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΠΈ ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΡ, ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π²ΠΎΡΠΏΠ°Π»Π΅Π½ΠΈΡ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΠ½ΡΠ΅Π³ΡΠ°Π»ΡΠ½ΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠ΅ ΠΏΠ»Π°Π·ΠΌΠ΅Π½Π½ΠΎΠ³ΠΎ Π³Π΅ΠΌΠΎΡΡΠ°Π·Π°. ΠΠΏΡΠ΅Π΄Π΅Π»ΡΠ»ΠΈ XIIa-Π·Π°Π²ΠΈΡΠΈΠΌΡΠΉ ΡΠΈΠ±ΡΠΈΠ½ΠΎΠ»ΠΈΠ·, ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ ΠΏΠ»Π°Π·ΠΌΠΈΠ½ΠΎΠ³Π΅Π½Π°, Π°Π»ΡΡΠ°2-Π°Π½ΡΠΈΠΏΠ»Π°Π·ΠΌΠΈΠ½Π°, ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡΠ° ΠΏΠ»Π°Π·ΠΌΠΈΠ½ΠΎΠ³Π΅Π½Π° 1 (PAI-1), ΡΠΈΠ±ΡΠΈΠ½ΠΎΠ³Π΅Π½Π°, ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΠ½ ΠΠΈΠ»Π»Π΅Π±ΡΠ°Π½Π΄Π° (FW), Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠ²Π΅ΡΡΡΠ²Π°Π½ΠΈΡ ΠΊΡΠΎΠ²ΠΈ VIII (FVIII), ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ Π²ΡΡΠΎΠΊΠΎΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π‘-ΡΠ΅Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ° ΠΈ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΡ ΡΠ΅ΡΡΠ° ΡΡΠΎΠΌΠ±ΠΎΠ΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ. ΠΡΠ΅ΠΌ Π±ΠΎΠ»ΡΠ½ΡΠΌ Π²ΡΠΏΠΎΠ»Π½Π΅Π½Π° ΠΌΠ°Π³Π½ΠΈΡΠ½ΠΎ-ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΠ½Π°Ρ ΡΠΎΠΌΠΎΠ³ΡΠ°ΡΠΈΡ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π° Ρ ΠΎΡΠ΅Π½ΠΊΠΎΠΉ ΠΏΠΎΡΠ°ΠΆΠ΅Π½ΠΈΡ Π±Π΅Π»ΠΎΠ³ΠΎ Π²Π΅ΡΠ΅ΡΡΠ²Π° ΠΏΠΎ ΡΠΊΠ°Π»Π΅ Π€Π°Π·Π΅ΠΊΠ°ΡΠ°.
Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ Π½Π°Π»ΠΈΡΠΈΡ Π½Π΅ΠΉΡΠΎΠ²ΠΈΠ·ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΎΠ½Π½ΡΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΠΠΠ‘ (ΠΎΡΠ΅Π½ΠΊΠ° ΠΏΠΎ ΡΠΊΠ°Π»Π΅ Π€Π°Π·Π΅ΠΊΠ°ΡΠ°) ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΠ΅ Π±ΡΠ»ΠΈ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Ρ Π² Π³ΡΡΠΏΠΏΡ Ρ ΠΠΠ‘ (n = 54) ΠΈ Π² Π³ΡΡΠΏΠΏΡ Π±Π΅Π· ΠΠΠ‘ (n = 63). ΠΠ°ΡΠΈΠ΅Π½ΡΡ Ρ ΠΠΠ‘ Π±ΡΠ»ΠΈ ΡΡΠ°ΡΡΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π±Π΅Π· ΠΠΠ‘ (65 9 ΠΏΡΠΎΡΠΈΠ² 51 10 Π»Π΅Ρ; p 0,001), Ρ Π½ΠΈΡ
ΡΠ°ΡΠ΅ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠΎΠ²Π°Π»ΠΈ Π³ΠΈΠΏΠ΅ΡΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΡΡ Π±ΠΎΠ»Π΅Π·Π½Ρ (p 0,001), ΡΠ°Ρ
Π°ΡΠ½ΡΠΉ Π΄ΠΈΠ°Π±Π΅Ρ (p = 0,029) ΠΈ ΡΡΠΎΠΌΠ±ΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠΎΠ±ΡΡΠΈΡ (p 0,001) Π² Π°Π½Π°ΠΌΠ½Π΅Π·Π΅. Π Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠ‘ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°ΠΌΠΈ Π±Π΅Π· ΠΠΠ‘ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ Π±ΠΎΠ»Π΅Π΅ Π΄Π»ΠΈΠ½Π½ΠΎΠ΅ Π²ΡΠ΅ΠΌΡ XIIa-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΡΠΈΠ±ΡΠΈΠ½ΠΎΠ»ΠΈΠ·Π° (7,6 2,9 ΠΏΡΠΎΡΠΈΠ² 6,5 1,7 ΠΌΠΈΠ½; Ρ = 0,032), Ρ Π½ΠΈΡ
Π±ΡΠ»Π° Π²ΡΡΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ Π°Π»ΡΡΠ°2-Π°Π½ΡΠΈΠΏΠ»Π°Π·ΠΌΠΈΠ½Π° (111 [95117] ΠΏΡΠΎΡΠΈΠ² 105 [95111]%; Ρ = 0,016) ΠΈ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡ ΠΏΠ»ΠΎΡΠ½ΠΎΡΡΠΈ ΡΠ³ΡΡΡΠΊΠ° (D) (22789 [2056726411] ΠΏΡΠΎΡΠΈΠ² 20627 [1832422650] Ρ.Π΅.; Ρ 0,001), Ρ
ΠΎΡΡ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ Π½Π°Ρ
ΠΎΠ΄ΠΈΠ»ΠΈΡΡ Π² ΡΠ΅ΡΠ΅ΡΠ΅Π½ΡΠ½ΡΡ
ΠΈΠ½ΡΠ΅ΡΠ²Π°Π»Π°Ρ
. Π§ΡΠΎ ΠΊΠ°ΡΠ°Π΅ΡΡΡ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΡΡΠΎΠΌΠ±ΠΎΠ΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ, Π² Π³ΡΡΠΏΠΏΠ΅ Ρ ΠΠΠ‘ Π½Π°Π±Π»ΡΠ΄Π°Π»ΠΈΡΡ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΈΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΏΠΎ Π²ΡΠ΅ΠΌ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠ°ΠΌ ΡΠ΅ΡΡΠ°, ΡΠ°ΠΊΠΆΠ΅ Π²ΡΡΠ²Π»Π΅Π½Ρ Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΈΠ΅ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² Π²ΠΎΡΠΏΠ°Π»Π΅Π½ΠΈΡ ΠΈ ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΠΈ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Ρ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ΠΌ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ XIIΠ°-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΡΠΈΠ±ΡΠΈΠ½ΠΎΠ»ΠΈΠ·Π° Π²ΠΎΠ·ΡΠ°ΡΡΠ°Π΅Ρ Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΡ 2-ΠΉ ΠΈ Π±ΠΎΠ»Π΅Π΅ ΡΡΠ°Π΄ΠΈΠΈ ΠΏΠ΅ΡΠΈΠ²Π΅Π½ΡΡΠΈΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ ΠΈ ΠΏΠΎΠ΄ΠΊΠΎΡΠΊΠΎΠ²ΠΎΠ³ΠΎ Π»Π΅ΠΉΠΊΠΎΠ°ΡΠ΅ΠΎΠ·Π° ΠΏΠΎ ΡΠΊΠ°Π»Π΅ Π€Π°Π·Π΅ΠΊΠ°ΡΠ° (ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ ΡΠ°Π½ΡΠΎΠ² (ΠΠ¨) 1,31 [1,071,60]; Ρ = 0,009), Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ ΡΠ°Π·ΠΌΠ΅ΡΠ° ΠΈ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΠΎΡΠ°Π³ΠΎΠ² Π³Π»ΠΈΠΎΠ·Π°, Π° ΠΏΡΠΈ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠΈ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΠΏΠ»Π°Π·ΠΌΠΈΠ½ΠΎΠ³Π΅Π½Π° Π²Π΅ΡΠΎΡΡΠ½ΠΎΡΡΡ Π»Π΅ΠΉΠΊΠΎΠ°ΡΠ΅ΠΎΠ·Π° ΠΏΠΎ ΡΠΊΠ°Π»Π΅ Π€Π°Π·Π΅ΠΊΠ°ΡΠ° ΡΠ½ΠΈΠΆΠ°Π΅ΡΡΡ (ΠΠ¨ 0,97 [0,950,98]; Ρ 0,001).
ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΡΡΡ Π½Π°ΡΡΡΠ΅Π½ΠΈΠΉ ΡΠΈΠ±ΡΠΈΠ½ΠΎΠ»ΠΈΠ·Π° ΠΈ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΎΠ² ΡΠΈΡΡΠ΅ΠΌΡ Π³Π΅ΠΌΠΎΡΡΠ°Π·Π° ΠΊΠΎΡΡΠ΅Π»ΠΈΡΡΠ΅Ρ Ρ ΡΡΠΆΠ΅ΡΡΡΡ ΠΠΠ‘ Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΌΠΎΠ·Π³Π°, ΡΠΎΡΠΌΠΈΡΡΡ Π³ΠΈΠΏΠΎΡΠΈΠ±ΡΠΈΠ½ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΈ ΠΏΡΠΎΡΡΠΎΠΌΠ±ΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΠ°ΡΡΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π΄Π°Π½Π½ΡΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ΠΌ