2,130 research outputs found
Imperfection of the system of the etalons attestation system
Π Π°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΡΠΎΠ±Π»Π΅ΠΌΡ, Π²ΠΎΠ·Π½ΠΈΠΊΠ°ΡΡΠΈΠ΅ Π½Π° ΠΏΡΡΠΈ ΠΊ ΡΡΠ²Π΅ΡΠΆΠ΄Π΅Π½ΠΈΡ ΡΡΠ°Π»ΠΎΠ½ΠΎΠ²Examined of main problems arising on the way to confirmation of etalon
Spectroscopy of Helium Isotope 6He
The excited states of heavy helium isotope 6He were studied in stopped pion absorption in the reactions 9Be
Current achievements in modifying crop genes using CRISPR/Cas system
With the advent of the new genome editing tool of target-specifically customizable endonucleases, a huge variety of novel opportunities have become feasible. The crop improvement is one of the main applications of genome editing in plant science and plant biotechnology. The amount of publications referring to genome editing and CRISPR/Cas system based molecular tools application in crops is permanently growing. The aim of this study is the systematization and cataloging of these data. Earlier we published the first catalog of targeted crop genome modifications as of February 10, 2017. The current review is an update of the catalog; it covers research papers on crop genome modifications from February 10, 2017 to August 17, 2018, found by searching 47 crop names in the Scopus database. Over one year and a half, 377 articles mentioning CRISPR/Cas and crop names have been published, of which 131 articles describe an experimental application of this tool for editing 193 genes in 19 crops, including rice with the largest number of genes modified (109 genes). Editing 50 of 193 genes was aimed at crop improvement. The catalog presented here includes these 50 genes, specifying the cultivars, each gene and gene product function, modification type and delivery method used. The current full list of genes modified with CRISPR/Cas with the aim of crop improvement is 81 in 16 crops (for 5 years from August 2013 to August 2018). In this paper, we also summarize data on different modifications types in different crops and provide a brief review of some novel methods and approaches that have appeared in crop genome editing research over the reviewed period. Taken together, these data provide a clear view on current progress in crop genome modifications and traits improvement using CRISPR/Cas based genome editing technology
Characterization of a novel dioxomolybdenum complex by cyclic voltammetry
Metalloenzymes that carry a pterin-based molybdenum cofactor in their center catalyze numerous reactions in the human body and play a crucial role in its metabolism. Specifically, these enzymes promote redox reactions and oxygen transport in the body. Their absence may cause many problems leading to disability or even death in early childhood. Therefore, model compounds need to be synthesized and analyzed to investigate the reactivity, redox potential, and geometry of these cofactors. This study focused on electrode processes and determined the redox potentials of the new bis-(4-mercapto-5-(p-tolyl)-3H-1,2-dithiole-3-thione)-dioxomolybdenum complex by cyclic voltammetry. The 4-mercapto-5-(p-tolyl)-3H-1,2-dithiole-3-thione ligand underwent irreversible oxidation and reduction at thiol and thione functional groups. The new dioxomolybdenum complex showed a quasi-reversible two-stage electrode process
Crop genes modified using CRISPR/Cas system
The CRISPR/Cas system is the most promising among genome editing tools. It can provide the development of modified nontransgenic plants with the possibility of simultaneous multiple targeted mutations. The purpose of this review is to analyze published papers describing the utilization of the CRISPR/Cas system for crop gene modification in order to assess the potential of this technology as a new plant breeding technique. The search for βCRISPR & crop nameβ within article titles, abstracts and keywords in the Scopus database was carried out for 45 crops. Among a total of 206 search results, only 88 have been recognized as original articles describing editing crop genes with the CRISPR/Cas system. A total of 145 target genes of 15 crops are described in these 88 articles, including rice with the largest number of genes modified (78 genes). In these studies, the ability to get transgene-free modified plants was widely demonstrated. However, in most cases research was aimed at the approbation of the technology or was to elucidate target gene function, while modification of just 37 target genes was related with crop improvement. We present here a catalogue of these genes. In most of these cases, modifications resulted in knockout of the genes such as negative growth and development regulators or negative regulators of plant resistance. In most cases, the phenotype of modified plants was assessed, and the presence of desired changes was shown. However, since the estimated number of βnegative regulatorsβ is limited in plant genomes, the CRISPR-directed gene knockout has a restricted potential for crop improvement. Intensive application of the CRISPR/Cas system for more complicate modifications such as replacement of defect alleles by functional ones or insertion of a desired gene is required (so far reports about such modifications are very rare in crops). In addition, to provide a basis for broad practical application of CRISPR/Cas-based genome editing, more cultivars of crop species should be involved in ongoing studies. Just a few genotypes of crop species have been used for gene modifications thus far. Nevertheless, in spite of the restrictions mentioned, essential success hasΒ been achieved over a short period (3.5 years since the first publications on CRISPR/Cas application in plants)
Anthropometric approach to the diagnosis of mandibular asymmetry
The article describes the possibilities of clinical and x-ray diagnostics of mandibular asymmetry. In 61.5% of cases, the asymmetry of the lower jaw is accompanied by complaints from patients about the presence of articular sounds, mild pain when opening the mouth. Asymmetry of the lower jaw is more often determined in female individuals aged 19 to 46 years.Π ΡΡΠ°ΡΡΠ΅ ΠΎΠΏΠΈΡΠ°Π½Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΈ ΡΠ΅Π½ΡΠ³Π΅Π½ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π°ΡΠΈΠΌΠΌΠ΅ΡΡΠΈΠΈ Π½ΠΈΠΆΠ½Π΅ΠΉ ΡΠ΅Π»ΡΡΡΠΈ. Π 61,5% ΡΠ»ΡΡΠ°Π΅Π² Π°ΡΠΈΠΌΠΌΠ΅ΡΡΠΈΡ Π½ΠΈΠΆΠ½Π΅ΠΉ ΡΠ΅Π»ΡΡΡΠΈ ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°Π΅ΡΡΡ ΠΆΠ°Π»ΠΎΠ±Π°ΠΌΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π½Π° Π½Π°Π»ΠΈΡΠΈΠ΅ ΡΡΡΡΠ°Π²Π½ΡΡ
Π·Π²ΡΠΊΠΎΠ², Π½Π΅ΡΠΈΠ»ΡΠ½ΠΎΠΉ Π±ΠΎΠ»ΠΈ ΠΏΡΠΈ ΠΎΡΠΊΡΡΠ²Π°Π½ΠΈΠΈ ΡΡΠ°. ΠΡΠΈΠΌΠΌΠ΅ΡΡΠΈΡ Π½ΠΈΠΆΠ½Π΅ΠΉ ΡΠ΅Π»ΡΡΡΠΈ ΡΠ°ΡΠ΅ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° Ρ Π»ΠΈΡ ΠΆΠ΅Π½ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΠ»Π° Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ ΠΎΡ 19 Π΄ΠΎ 46 Π»Π΅
Neuropsychological Tests in Researches of Executive Functions in Adults With Attention β Deficit / Hyperactivity Syndrome
Π¦Π΅Π»ΡΡ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΎΠ±Π·ΠΎΡΠ° ΡΠ²Π»ΡΠ΅ΡΡΡ Π°Π½Π°Π»ΠΈΠ· ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π‘ΠΠΠ Ρ Π²Π·ΡΠΎΡΠ»ΡΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ². ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΠΊΠ°Π·ΡΠ²Π°ΡΡ Π½Π°ΡΡΡΠ΅Π½ΠΈΠ΅ ΠΈΡΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΡΡΠ½ΠΊΡΠΈΠΉ Ρ Π΄Π΅ΡΠ΅ΠΉ Ρ Π‘ΠΠΠ, ΠΎΠ΄Π½Π°ΠΊΠΎ Π½Π΅ ΡΠ°ΠΊ ΠΌΠ½ΠΎΠ³ΠΎ ΡΠ°Π±ΠΎΡ ΠΏΠΎΡΠ²ΡΡΠ΅Π½ΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΠΈΡΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΡΡΠ½ΠΊΡΠΈΠΉ Ρ Π²Π·ΡΠΎΡΠ»ΡΡ
. ΠΠΎΠΌΠΈΠΌΠΎ ΡΡΠΎΠ³ΠΎ, Π² ΠΎΡΠ΅Π½ΠΊΠ΅ ΠΈ ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠΈ ΠΈΡΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΡΡΠ½ΠΊΡΠΈΠΉ ΠΎΡΡΡΡΡΡΠ²ΡΡΡ Π½Π΅ΠΉΡΠΎΠΏΡΠΈΡ
ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ°ΡΠΊΠ΅ΡΡ.The aim of this review is to analyze diagnostic tools for ADHD in adult patients. There are large body of literature on executive functions impairment in ADHD children; however a lack of researches is account to the study of executive functions in adults. Furthermore, there are no neuropsychological markers in the assessment and measurement of executive functions
STUDY UNIFORM DISTRIBUTION OF ELEMENTS IN THE OXIDE DISPERSIVE STRENGTHENED STEEL
The distribution of elements in the oxide dispersive strengthened steel at the outputted proton beam into the atmosphere is study. TheΒ experiments were performed on an analytical nuclear-physical complex "Sokol" is study. For the analysis of the samples obtainedΒ were used vacuum arc melting of steel industry 08Cr18Ni10Ti into which the hardening particles ZrO2 stabilized Y2O3, with a size ofΒ 0.1 β 0.5 microns. Mathematical processing of spectral data obtained by mass composition of basic elements and doping impuritiesΒ studied oxide dispersive strengthened steel. The uniformity of the distribution of elements was studied on entire surface of theΒ sample
ΠΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»ΠΈΠ·ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΡΡ ΡΠΈΡΡΠ΅ΠΈΠ½ΠΎΠ²ΡΡ ΠΏΡΠΎΡΠ΅Π°Π· ΠΏΠ»Π°Π·ΠΌΡ, ΠΌΠΎΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΡ ΠΈ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΡ Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠΎΠ² ΠΊΡΠΎΠ²ΠΈ ΠΏΡΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΠΠ»ΡΡΠ³Π΅ΠΉΠΌΠ΅ΡΠ°
Aim. To study the level of activity of lysosomal cysteine proteases (cathepsins H, B, L) in blood plasma andΒ fractionated leukocytes (polymorphonuclear and mononuclear) in patients with Alzheimerβs disease in comparisonΒ with similar indicators in persons without signs of neurodegeneration as a possible marker of Alzheimerβs diseaseΒ development and diagnosis.Materials and methods. The spectrofluorimetric study of cathepsins B, L, H activity level in plasma andΒ fractionated leukocytes was conducted in 22 patients diagnosed with Alzheimerβs disease in comparison with theΒ same indicators in 22 patients matched by sex, age and associated diseases with patients of the observation group,Β but having no signs of neurodegeneration.Results. The activity of all three enzymes, and especially cathepsin H, increased significantly in blood plasma.Β A significant increase is also noted in the activity of cathepsins H, B, and L in homogenates of fractionatedΒ leukocytes. AtΒ the same time, in both polymorphonuclear and mononuclear leukocytes the greatest degree of changes is demonstratedΒ by the activity of cathepsin B, and the least is the activity of cathepsin L. Given the available data on an increasedΒ cathepsin B activity in the cerebrospinal fluid of patients with Alzheimerβs disease, we can assume a correlationΒ between the state of lysosomal proteases activity in the Central nervous system and in the peripheral blood cells.Conclusion. Alzheimerβs disease is associated with increased activity of cysteine cathepsins in plasma,Β polymorphonuclear and mononuclear leukocytes of peripheral blood, which can be considered as one of theΒ possible markers of development and diagnosis of the disease.Β Β Π¦Π΅Π»Ρ. ΠΠ·ΡΡΠΈΡΡ ΡΡΠΎΠ²Π΅Π½Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»ΠΈΠ·ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΡΡ
ΡΠΈΡΡΠ΅ΠΈΠ½ΠΎΠ²ΡΡ
ΠΏΡΠΎΡΠ΅ΠΈΠ½Π°Π· (ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½ΠΎΠ² H, B, L) Π² ΠΏΠ»Π°Π·ΠΌΠ΅Β ΠΊΡΠΎΠ²ΠΈ ΠΈ ΡΡΠ°ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠ°Ρ
(ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΡ
ΠΈ ΠΌΠΎΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΡ
) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π±ΠΎΠ»Π΅Π·Π½ΡΡΒ ΠΠ»ΡΡΠ³Π΅ΠΉΠΌΠ΅ΡΠ° Π² ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ Ρ Π°Π½Π°Π»ΠΎΠ³ΠΈΡΠ½ΡΠΌΠΈ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΡΠΌΠΈ Ρ Π»ΠΈΡ, Π½Π΅ ΠΈΠΌΠ΅ΡΡΠΈΡ
ΠΏΡΠΈΠ·Π½Π°ΠΊΠΎΠ² Π½Π΅ΠΉΡΠΎΠ΄Π΅Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠΈ,Β ΠΊΠ°ΠΊ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΠΉ ΠΌΠ°ΡΠΊΠ΅Ρ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΈ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π±ΠΎΠ»Π΅Π·Π½ΠΈ ΠΠ»ΡΡΠ³Π΅ΠΉΠΌΠ΅ΡΠ°.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠ»ΡΠΎΡΠΈΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½ΠΎΠ²Β B, L, H Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ ΠΈ ΡΡΠ°ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠ°Ρ
22 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π΄ΠΈΠ°Π³Π½ΠΎΠ·ΠΎΠΌ Β«ΠΠΎΠ»Π΅Π·Π½Ρ ΠΠ»ΡΡΠ³Π΅ΠΉΠΌΠ΅Ρа» в ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ Ρ Π°Π½Π°Π»ΠΎΠ³ΠΈΡΠ½ΡΠΌΠΈ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΡΠΌΠΈ 22 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΠΌΡΡ
ΠΏΠΎ ΠΏΠΎΠ»Ρ, Π²ΠΎΠ·ΡΠ°ΡΡΡ ΠΈ ΡΠΎΠΏΡΡΡΡΠ²ΡΡΡΠΈΠΌΒ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΠΌ Ρ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ°ΠΌΠΈ Π³ΡΡΠΏΠΏΡ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΡ, Π½ΠΎ Π½Π΅ ΠΈΠΌΠ΅ΡΡΠΈΡ
Β ΠΏΡΠΈΠ·Π½Π°ΠΊΠΎΠ² Π½Π΅ΠΉΡΠΎΠ΄Π΅Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎ ΠΏΠΎΠ²ΡΡΠ΅Π½Π° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π²ΡΠ΅Ρ
ΡΡΠ΅Ρ
ΡΠ΅ΡΠΌΠ΅Π½ΡΠΎΠ²,Β Π² Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠ΅ΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ β Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½Π° Π. Π Π³ΠΎΠΌΠΎΠ³Π΅Π½Π°ΡΠ°Ρ
ΡΡΠ°ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠΎΠ²Β ΡΠ°ΠΊΠΆΠ΅ ΠΎΡΠΌΠ΅ΡΠ°Π΅ΡΡΡ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎΠ΅ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½ΠΎΠ² Π, B, L, ΠΏΡΠΈ ΡΡΠΎΠΌ ΠΊΠ°ΠΊ Π²Β ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΡ
, ΡΠ°ΠΊ ΠΈ Π² ΠΌΠΎΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΡ
Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠ°Ρ
Π² Π½Π°ΠΈΠ±ΠΎΠ»ΡΡΠ΅ΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ ΠΈΠ·ΠΌΠ΅Π½ΡΠ΅ΡΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΒ ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½Π° Π, Π½Π°ΠΈΠΌΠ΅Π½ΡΡΠ΅ΠΉ βΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½Π° L. Π£ΡΠΈΡΡΠ²Π°Ρ ΠΈΠΌΠ΅ΡΡΠΈΠ΅ΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½Π°Β Π Π² ΡΠ΅ΡΠ΅Π±ΡΠΎΡΠΏΠΈΠ½Π°Π»ΡΠ½ΠΎΠΉ ΠΆΠΈΠ΄ΠΊΠΎΡΡΠΈ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π±ΠΎΠ»Π΅Π·Π½ΡΡ ΠΠ»ΡΡΠ³Π΅ΠΉΠΌΠ΅ΡΠ°, ΠΌΠΎΠΆΠ½ΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·ΡΒ ΠΌΠ΅ΠΆΠ΄Ρ ΡΠΎΡΡΠΎΡΠ½ΠΈΠ΅ΠΌ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π»ΠΈΠ·ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΡΡ
ΠΏΡΠΎΡΠ΅ΠΈΠ½Π°Π· Π² ΡΠ΅Π½ΡΡΠ°Π»ΡΠ½ΠΎΠΉ Π½Π΅ΡΠ²Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΠ΅ ΠΈ ΠΏΠ΅ΡΠΈΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
Β ΠΊΠ»Π΅ΡΠΊΠ°Ρ
ΠΊΡΠΎΠ²ΠΈ.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠ»Π΅Π·Π½Ρ ΠΠ»ΡΡΠ³Π΅ΠΉΠΌΠ΅ΡΠ° Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Π° Ρ Π½Π°ΡΠ°ΡΡΠ°Π½ΠΈΠ΅ΠΌ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠΈΡΡΠ΅ΠΈΠ½ΠΎΠ²ΡΡ
ΠΊΠ°ΡΠ΅ΠΏΡΠΈΠ½ΠΎΠ² Π²Β ΠΏΠ»Π°Π·ΠΌΠ΅, ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΡ
ΠΈ ΠΌΠΎΠ½ΠΎΡΠ΄Π΅ΡΠ½ΡΡ
Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠ°Ρ
ΠΏΠ΅ΡΠΈΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΡΠΎΠ²ΠΈ, ΡΡΠΎ ΠΌΠΎΠΆΠ΅Ρ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡΡΡΒ ΠΊΠ°ΠΊ ΠΎΠ΄ΠΈΠ½ ΠΈΠ· Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΡ
ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΈ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ
Π‘ΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½Π½ΡΠΌ ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·ΠΈΡΡΡΡΠΈΠΌ ΡΠΎΡΡΠ°Π²ΠΎΠΌ
Scientific relevance. The national and international human albumin preparations registered in the Russian Federation mainly differ in their excipient compositions. While all the international preparations of human albumin contain a mixture of sodium caprylate and N-acetyl-DL-tryptophan, the Russian ones contain only sodium caprylate. However, albumin stabilisation with sodium caprylate at high concentrations affects the ligand-binding properties of albumin. For this reason, as well as to achieve storage stability not only at temperatures of 2 Β°C to 8 Β°C but alsoΒ Β at room temperature, most international manufacturers have reduced the sodium caprylate content in albumin preparations and added N-acetyl-DL-tryptophan. This demonstrates the relevance of studying the quality of a new Russian human albumin preparation with a modified stabilising composition, including both sodium caprylate and N-acetyl-DL-tryptophan.Aim. The study aimed at comparing several quality attributes of the human albumin preparation with a modified stabilising composition with those of imported human albumin preparations.Materials and methods. The human albumin preparation with a modified stabilising composition was manufactured by fractionation from donor plasma meeting the requirements of monograph FS.3.3.2.0001.19 of the State Pharmacopoeia of the Russian Federation edition XIV. The quality control was in line with the monograph on human albumin (FS.3.3.2.0006.18), and statistical analysis was conducted in Microsoft Excel in accordance with the general chapter on statistical analysis (OFS.1.1.0013.15).Results. The study preparation complied with the requirements specified in monograph FS.3.3.2.0006.18. All the manufactured batches were clear, thermostable, sterile, and non-pyrogenic. The prekallikrein activator levels were low (below 1 IU/mL). The aluminium content varied from 30.36Β±10.39 Β΅g/L to 50.22Β±6.94 Β΅g/L. The study preparation contained sodium ions at a concentration from 127.44Β±10.46 mmol/L to 145.59Β±7.32 mmol/L and less than 0.01 mmol/g of potassium ions. The osmolarity exceeded 240 mOsm/L. The content of Ξ±- and Ξ²-globulinsΒ rangedΒ fromΒ 1.79Β±0.06%Β toΒ 2.24Β±0.20%.Β TheΒ studyΒ preparationΒ hadΒ aΒ pHΒ levelΒ of 6.9 to 7.2. The concentrations of polymers and aggregates did not exceed 0.5%.Conclusions. The quality attributes studied suggest that the human albumin preparation withΒ Β a modified stabilising composition is comparable to its international counterparts and that it meets Russian and European pharmacopoeial standards.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ. ΠΠ°ΡΡΠ±Π΅ΠΆΠ½ΡΠ΅ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°, Π·Π°ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ Π² Π ΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ Π€Π΅Π΄Π΅ΡΠ°ΡΠΈΠΈ, ΠΎΡΠ»ΠΈΡΠ°ΡΡΡΡ ΠΎΡ ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
Π³Π»Π°Π²Π½ΡΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ ΠΏΠΎ ΡΠΎΡΡΠ°Π²Ρ Π²ΡΠΏΠΎΠΌΠΎΠ³Π°ΡΠ΅Π»ΡΠ½ΡΡ
Π²Π΅ΡΠ΅ΡΡΠ². ΠΡΠ΅ ΠΈΠ½ΠΎΡΡΡΠ°Π½Π½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° ΡΠΎΠ΄Π΅ΡΠΆΠ°Ρ ΡΠΌΠ΅ΡΡ Π²ΡΠΏΠΎΠΌΠΎΠ³Π°ΡΠ΅Π»ΡΠ½ΡΡ
Π²Π΅ΡΠ΅ΡΡΠ² β Π½Π°ΡΡΠΈΡ ΠΊΠ°ΠΏΡΠΈΠ»Π°ΡΠ° ΠΈ N-Π°ΡΠ΅ΡΠΈΠ»-DL-ΡΡΠΈΠΏΡΠΎΡΠ°Π½Π°; ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠ΅ β ΡΠΎΠ»ΡΠΊΠΎ Π½Π°ΡΡΠΈΡ ΠΊΠ°ΠΏΡΠΈΠ»Π°Ρ. ΠΠ΄Π½Π°ΠΊΠΎ ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΡ ΡΠ°ΡΡΠ²ΠΎΡΠ° Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° Π½Π°ΡΡΠΈΡ ΠΊΠ°ΠΏΡΠΈΠ»Π°ΡΠΎΠΌ Π² Π²ΡΡΠΎΠΊΠΈΡ
ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ
ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΡΡ
ΡΠ΄ΡΠ΅Π½ΠΈΡ Π΅Π³ΠΎ Π»ΠΈΠ³Π°Π½Π΄ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ
ΡΠ²ΠΎΠΉΡΡΠ². ΠΠΎ ΡΡΠΎΠΉ ΠΏΡΠΈΡΠΈΠ½Π΅, Π° ΡΠ°ΠΊΠΆΠ΅ Π΄Π»Ρ Π΄ΠΎΡΡΠΈΠΆΠ΅Π½ΠΈΡ ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΡΠΈ Ρ
ΡΠ°Π½Π΅Π½ΠΈΠΈ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ ΠΏΡΠΈ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ΅ ΠΎΡ 2 Π΄ΠΎ 8 Β°C, Π½ΠΎ ΠΈ ΠΏΡΠΈ ΠΊΠΎΠΌΠ½Π°ΡΠ½ΠΎΠΉ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ΅, Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎ Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΡ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΠΈΡΠ΅Π»Π΅ΠΉ ΠΈΠ·ΠΌΠ΅Π½ΠΈΠ»ΠΈ ΡΠΎΡΡΠ°Π² ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° ΠΏΡΡΠ΅ΠΌ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ Π½Π°ΡΡΠΈΡ ΠΊΠ°ΠΏΡΠΈΠ»Π°ΡΠ° ΠΈ Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ N-Π°ΡΠ΅ΡΠΈΠ»-DL-ΡΡΠΈΠΏΡΠΎΡΠ°Π½Π°. Π ΡΠ²ΡΠ·ΠΈ Ρ ΡΡΠΈΠΌ Π°ΠΊΡΡΠ°Π»ΡΠ½ΡΠΌ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΠΎΠ³ΠΎ ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½Π½ΡΠΌ ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·ΠΈΡΡΡΡΠΈΠΌ ΡΠΎΡΡΠ°Π²ΠΎΠΌ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠΌ ΠΎΠ±Π° ΡΠΊΠ°Π·Π°Π½Π½ΡΡ
ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ°.Π¦Π΅Π»Ρ. ΠΠ½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½Π½ΡΠΌ ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·ΠΈΡΡΡΡΠΈΠΌ ΡΠΎΡΡΠ°Π²ΠΎΠΌ Π² ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ Ρ Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΠΌΠΈ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠΌΠΈ ΡΡΠ΅Π΄ΡΡΠ²Π°ΠΌΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠΊΡΠΈΠ²Π½ΠΎΠΉ ΡΠ°ΡΠΌΠ°ΡΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΡΠ±ΡΡΠ°Π½ΡΠΈΠ΅ΠΉ Π΄Π»Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Ρ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½Π½ΡΠΌ ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·ΠΈΡΡΡΡΠΈΠΌ ΡΠΎΡΡΠ°Π²ΠΎΠΌ ΡΠ»ΡΠΆΠΈΠ»Π° ΠΏΠ»Π°Π·ΠΌΠ° ΠΊΡΠΎΠ²ΠΈ Π΄ΠΎΠ½ΠΎΡΠΎΠ², ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠ°Ρ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡΠΌ ΠΠΎΡΡΠ΄Π°ΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΏΠ΅ΠΈ Π ΠΎΡΡΠΈΠΉΡΠΊΠΎΠΉ Π€Π΅Π΄Π΅ΡΠ°ΡΠΈΠΈ XIV ΠΈΠ·Π΄. (ΠΠ€ Π Π€ XIV) Π€Π‘.3.3.2.0001.19. ΠΡΠ΅ΠΏΠ°ΡΠ°Ρ ΠΏΠΎΠ»ΡΡΠ°Π»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΡΠ°ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΏΠ»Π°Π·ΠΌΡ ΠΊΡΠΎΠ²ΠΈ. ΠΠΎΠ½ΡΡΠΎΠ»Ρ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ»ΠΈ Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡΠΌΠΈΒ Π€Π‘.3.3.2.0006.18.Β Π‘ΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΡΡ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΡ Microsoft Excel Π² ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠΈ Ρ ΠΠ€Π‘.1.1.0013.15.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΈΠ΅ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π½ΡΠΌ ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡΠΌΒ Π€Π‘.3.3.2.0006.18. Π Ρ
ΠΎΠ΄Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉΒ Β ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ,Β ΡΡΠΎ ΠΈΠ·Π³ΠΎΡΠΎΠ²Π»Π΅Π½Π½ΡΠ΅ ΡΠ΅ΡΠΈΠΈΒ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° Π±ΡΠ»ΠΈ ΠΏΡΠΎΠ·ΡΠ°ΡΠ½ΡΠΌΠΈ,Β ΡΠ΅ΡΠΌΠΎΡΡΠ°Π±ΠΈΠ»ΡΠ½ΡΠΌΠΈ, ΡΡΠ΅ΡΠΈΠ»ΡΠ½ΡΠΌΠΈΒ ΠΈ Π°ΠΏΠΈΡΠΎΠ³Π΅Π½Π½ΡΠΌΠΈ; ΠΈΠΌΠ΅Π»ΠΈ Π½ΠΈΠ·ΠΊΠΈΠΉ ΡΡΠΎΠ²Π΅Π½Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΎΡΠ° ΠΏΡΠ΅ΠΊΠ°Π»Π»ΠΈΠΊΡΠ΅ΠΈΠ½Π° β ΠΌΠ΅Π½Π΅Π΅ 1 ΠΠ/ΠΌΠ»; ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ Π°Π»ΡΠΌΠΈΠ½ΠΈΡ Π±ΡΠ»ΠΎ Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΠΎΡ 30,36Β±10,39 Π΄ΠΎΒ 50,22Β±6,94Β ΠΌΠΊΠ³/Π»;Β Π½Π°ΡΡΠΈΠΉ-ΠΈΠΎΠ½Π° β ΠΎΡ 127,44Β±10,46 Π΄ΠΎ 145,59Β±7,32 ΠΌΠΌΠΎΠ»Ρ/Π»; ΠΊΠ°Π»ΠΈΠΉ-ΠΈΠΎΠ½Π° β ΠΌΠ΅Π½Π΅Π΅ 0,01 ΠΌΠΌΠΎΠ»Ρ/Π³; ΠΎΡΠΌΠΎΠ»ΡΡΠ½ΠΎΡΡΡ β Π±ΠΎΠ»Π΅Π΅ 240 ΠΌΠΡΠΌ/Π». ΠΡΠ΅ΠΏΠ°ΡΠ°Ρ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π» ΠΎΡ 1,79Β±0,06 Π΄ΠΎ 2,24Β±0,20% ΠΏΡΠΈΠΌΠ΅ΡΠ΅ΠΉ Π΄ΡΡΠ³ΠΈΡ
Π±Π΅Π»ΠΊΠΎΠ²Β (Ξ±- ΠΈ Ξ²-Π³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ΠΎΠ²); ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Ρ ΡΠ Π±ΡΠ» Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΠΎΡ 6,9 Π΄ΠΎ 7,2;Β ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡ ΠΏΠΎΠ»ΠΈΠΌΠ΅ΡΠΎΠ²Β Β Β ΠΈ Π°Π³ΡΠ΅Π³Π°ΡΠΎΠ² Π½Π΅ ΠΏΡΠ΅Π²ΡΡΠ°Π»Π° 0,5%.ΠΡΠ²ΠΎΠ΄Ρ. ΠΠΎ ΠΈΠ·ΡΡΠ΅Π½Π½ΡΠΌ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΡΠΌ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ Π°Π»ΡΠ±ΡΠΌΠΈΠ½Π° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°Β ΡΒ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½Π½ΡΠΌ ΡΡΠ°Π±ΠΈΠ»ΠΈΠ·ΠΈΡΡΡΡΠΈΠΌ ΡΠΎΡΡΠ°Π²ΠΎΠΌ Π±ΡΠ» ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΠΌ Ρ Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΠΌΠΈ Π°Π½Π°Π»ΠΎΠ³Π°ΠΌΠΈ ΠΈ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΠΎΠ²Π°Π» ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΡΠΌ ΠΠ€ Π Π€ XIV ΠΈ ΠΠ²ΡΠΎΠΏΠ΅ΠΉΡΠΊΠΎΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠΏΠ΅ΠΈ
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