44 research outputs found
Risk Factors and Characteristics of Adverse Reactions Associated with the Use of Beta-Lactam Antibiotics in Older Patients
The frequency of adverse drug reactions (ADRs) in older patients is approximately 11.0%, according to scientific literature. Antibiotics are the third largest group (19.5%) of medicinal products in terms of ADR frequency in geriatric patients. Beta-lactam antibiotics are the empiric treatment of choice for older outpatients and inpatients with community-acquired pneumonia. The mortality in this group of patients accounts for 85% of the overall mortality from community-acquired pneumonia. The aim of the study was to analyse scientific data on risk factors and characteristics of adverse drug reactions associated with the use of beta-lactam antibiotics in older patients. Specificity of ADRs to beta-lactam antibiotics in this group of patients is due to age-related changes in pharmacokinetics and pharmacodynamics as well as polymorbidity and polypharmacy. The analysis of scientific literature demonstrated that there have not been so many pharmacoepidemiological studies in this group of patients, and their results have been inconsistent. The frequency, causes, and clinical manifestations of ADRs in geriatric patients are diverse and differ considerably from those in younger patients. Of the most widely used antibiotics, ceftriaxone and cefaclor exhibited a statistically lower risk of ADRs in older patients than in younger patients. AtΒ the same time, ceftriaxone was associated with a relatively higher frequency of serious ADRs in older patients as compared to younger patients, whereas the frequency of serious ADRs was lower with cefaclor. The likelihood of nephrotoxic, neurotoxic, and hepatotoxic ADRs associated with the use of beta-lactam antibiotics is becoming more and more obvious but it is still underestimated in clinical and geriatric practice. Safety monitoring, therapeutic drug monitoring with due consideration of ADR risk factors in older patients, and inclusion of older patients in clinical trials of antimicrobial drugs, would improve efficacy and safety of antibiotic treatment
First results of the Kourovka Planet Search: discovery of transiting exoplanet candidates in the first three target fields
We present the first results of our search for transiting exoplanet
candidates as part of the Kourovka Planet Search (KPS) project. The primary
objective of the project is to search for new hot Jupiters which transit their
host stars, mainly in the Galactic plane, in the magnitude range of 11 to
14 mag. Our observations were performed with the telescope of the MASTER
robotic network, installed at the Kourovka astronomical observatory of the Ural
Federal University (Russia), and the Rowe-Ackermann Schmidt Astrograph,
installed at the private Acton Sky Portal Observatory (USA). As test
observations, we observed three celestial fields of size deg
during the period from 2012 to 2015. As a result, we discovered four transiting
exoplanet candidates among the 39000 stars of the input catalogue. In this
paper, we provide the description of the project and analyse additional
photometric, spectral, and speckle interferometric observations of the
discovered transiting exoplanet candidates. Three of the four transiting
exoplanet candidates are most likely astrophysical false positives, while the
nature of the fourth (most promising) candidate remains to be ascertained.
Also, we propose an alternative observing strategy that could increase the
project's exoplanet haul.Comment: 11 pages, 16 figures; Accepted for publication in Monthly Notices of
the Royal Astronomical Society 201
Nephrotoxicity Biomarkers: Role and Significance in the Diagnosis of Drug-Induced Kidney Injury
Drug-induced kidney injury (DIKI) accounts for 8 to 60% of episodes of acute kidney injury (AKI) among hospital patients. Early DIKI detection and timely adjustment of therapy will help reduce the kidney injury incidence and mortality. The aim of the study was to analyse scientific literature on the biomarkers used in DIKI diagnosis. The study revealed that the use of such kidney damage markers as serum creatinine, urinary output, urea nitrogen, sodium excretion, urinary sediment microscopy is limited because they do not give a full picture of the kidney injury degree and progression and do not allow for early AKI diagnosis. It was demonstrated that some of the most promising biomarkers are KIM-1, L-FABP, NAG, NGAL, cystatin C, clusterin, Ξ²2-microglobulin, ΠΠ‘Π -1, IGFBP7, and TIMP-2. However, recommendations for determination of these biomarkersβ urine or blood concentrations for AKI diagnosis are somewhat preliminary, because there have been insufficient clinical and preclinical studies to establish validity of such tests. No precise algorithms based on determination of the biomarkers levels in urea and/or blood serum have been developed for AKI risk assessment, diagnosis, monitoring, and treatment. Thus, further research is necessary to investigate different AKI biomarkers and improve experimental models (both in vivo and in vitro), which will support assessment of potential nephrotoxic properties of existing and new medicinal products
Evaluation of the Efficacy and Safety of Initial Empirical Antibiotic Therapy for Community-Acquired Pneumonia in Middle-Aged People
Ξ²-lactam antibiotics, including cephalosporins, are the drugs of choice for empirical antibiotic therapy (ABT) in patients with community-acquired pneumonia. Unreasonable and irrational use of antibiotics leads to an increased risk of adverse reactions, contributes to the growth of antibiotic resistance.The aim of the study was to analyse data on the efficacy and safety of initial empirical ABT using cephalosporins for community-acquired pneumonia in middle-aged patients of multidisciplinary hospitals in Moscow.Materials and methods: the authors analysed 177 archived medical records of the patients admitted to three multidisciplinary hospitals (I.V. Davydovsky City Clinical Hospital, City Clinical Hospital 52 and City Clinical Hospital 4) in Moscow from 2017 to 2019 and prescribed mono- and/or combination therapy including a cephalosporin antibiotic as a starting therapy for community-acquired pneumonia. The initial ABT was considered effective if a patientβs body temperature normalised within 48β72 h following initiation of treatment and safe if no adverse reactions developed during the period of inpatient treatment.Results: the combination of ceftriaxone and azithromycin was the most frequently prescribed ABT regimen; its effectiveness was 71.9%. Ceftriaxone monotherapy was the second in frequency of prescription; its effectiveness amounted to 77.2%. The third regimen included cefotaxime and azithromycin and was effective in 70% of cases. The patients who needed a change in initial ABT had a significantly higher incidence of developing severe community-acquired pneumonia and complications. The study results indicate that the structure of comorbidity did not affect the effectiveness of initial empirical ABT. Streptococcus pneumoniae was found to be the most common causative agent of community-acquired pneumonia in the studied population (44.8% of cases). Only 13% of the patients faced adverse reactions associated with the use of antibiotics as part of the initial empirical ABT; the most common were leukopenia and diarrhoea.Π‘onclusions: the results of the study indicate the feasibility of mono- and/or combination ABT including a cephalosporin antibiotic as a starting empirical therapy for community-acquired pneumonia due to its effectiveness and favourable safety profile
Antibiotic Dosing in Chronic Kidney Disease
Infectious process is an important cause of morbidity and mortality among patients with chronic kidney disease. Prescription of antibacterial drugs should take into account the pharmacokinetic parameters of the medicine and the individual characteristics of the patient. Adequate antibiotic dosing is crucial for positive treatment outcome and minimisation of side effects. The aim of the study was to analyse scientific literature on factors affecting the dosing of antibacterials in patients with chronic kidney disease. Since most antibacterial medicines are eliminated by the kidneys, a decrease in glomerular filtration rate or kidney function should be followed by the dose adjustment in order to prevent the medicine accumulation and reduce the risk of side effects. Antibiotic dosing in such patients should be accompanied by kidney function assessment and be adjusted to ensure effective and safe treatment, as well as prevention of bacterial resistance. The review provides data on the dosing of some antibiotic groups (beta-lactams, aminoglycosides, fluoroquinolones) at different creatinine clearance rates. Extrarenal excretion of medicines does not usually require the dose adjustment in patients with chronic kidney disease
Retrospective Analysis of the Safety of Antibacterial Medicinal Products for Elderly Patients with Community-Acquired Lower Respiratory Tract Infections
Cephalosporins are the empirical antibiotic therapy (ABT) of choice for patients with community-acquired pneumonia (CAP). When treated with antibiotics, elderly patients, especially those with comorbidities, are at higher risk of developing adverse drug reactions (ADRs).The aim of the study was to analyse data on the safety and efficacy of initial empirical ABT with cephalosporins in elderly patients over 75 years old with CAP admitted to multidisciplinary hospitals in Moscow.Materials and methods. The retrospective study included 305 medical records of patients with CAP admitted to three multidisciplinary hospitals in Moscow in 2017β2019 and prescribed initial mono- and/or combination ABT including a cephalosporin. Initial ABT was considered effective if the body temperature normalised within 48β72 h from the start of treatment. It was considered safe if there were no ADRs during hospital stay.Results. Mostly, patients were prescribed ceftriaxone monotherapy or ceftriaxone and azithromycin combination therapy. These ABT regimens were effective in 69.07% and 78.10% of the cases, respectively. Patients with severe CAP needed their initial ABT adjusted significantly more often than those with non-severe CAP. The initial ABT was changed for a number of reasons, including ineffectiveness, ADRs, abscesses formed as a complication of CAP, sputum culture results enabling causal ABT, secondary hospital-acquired infections, and exacerbated chronic infections. All patients had comorbidities, and the most prevalent were arterial hypertension (83.9%), coronary heart disease (45.6%), chronic heart failure (44.9%), cerebrovascular disease (40.9%), atrial fibrillation (26.9%), diabetes mellitus (21.3%), and chronic obstructive pulmonary disease (19.0%). Initial ABT was significantly more often considered ineffective in patients with chronic heart failure and cerebrovascular disease. The most common causative agent of CAP in the study population was Streptococcus pneumoniae (31.9%). In 16% of patients, the authors identified ADRs associated with the antibiotics used as initial therapy. The most common were diarrhoea, anaemia, leucopenia, and hepatopathy. Ceftriaxone was associated with ADRs in 11% of patients.Conclusions. The study results suggest that initial mono- and/or combination ABT including a cephalosporin is effective and relatively safe; therefore, this treatment option is expedient for elderly patients with CAP. For this population, the safety of ABT may be improved through the wider use of existing markers of ADRs and the identification of new ones
ΠΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ ΡΡΠ΅Π΄ΡΡΠ² Ρ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ : ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ ΠΎΠΆΠΈΠ΄Π°Π΅ΠΌΠΎΠΉ ΠΏΠΎΠ»ΡΠ·Ρ ΠΊ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠΌΡ ΡΠΈΡΠΊΡ?
In terms of pharmacotherapy, pregnancy is a specific phase of life that is different from all the other phases of the life of medical, ethical and legal framework. The article examines the scientific, ethical and regulatory principles of inclusion of pregnant women in the clinical trials of drugs, the necessity for them is justified from the point of clinical pharmacology. The clinical value assessment studies regarding the expected benefits to the possible risks during the pharmacotherapy in pregnancy necessitates the development of this scientific direction.Π‘ ΡΠΎΡΠΊΠΈ Π·ΡΠ΅Π½ΠΈΡ ΡΠ°ΡΠΌΠ°ΠΊΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΡΡΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΡΠΎΠ±ΠΎΠΉ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΡΡ ΡΠ°Π·Ρ ΠΆΠΈΠ·Π½ΠΈ, ΠΊΠΎΡΠΎΡΠ°Ρ ΠΎΡΠ»ΠΈΡΠ°Π΅ΡΡΡ ΠΎΡ Π²ΡΠ΅Ρ
Π΄ΡΡΠ³ΠΈΡ
ΡΠ°Π· ΠΆΠΈΠ·Π½ΠΈ ΠΏΠΎ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΈΠΌ, ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΈ ΠΏΡΠ°Π²ΠΎΠ²ΡΠΌ ΠΎΡΠ½ΠΎΠ²Π°ΠΌ. Π ΡΡΠ°ΡΡΠ΅ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡΡΡ Π½Π°ΡΡΠ½ΡΠ΅, ΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠ΅ ΠΏΡΠΈΠ½ΡΠΈΠΏΡ Π²ΠΊΠ»ΡΡΠ΅Π½ΠΈΡ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΠΆΠ΅Π½ΡΠΈΠ½ Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΡΡΠ΅Π΄ΡΡΠ², ΠΎΠ±ΠΎΡΠ½ΠΎΠ²ΡΠ²Π°Π΅ΡΡΡ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΠΈΡ
ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Ρ ΠΏΠΎΠ·ΠΈΡΠΈΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΠΈ. ΠΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠ΅Π½Π½ΠΎΡΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎ ΠΎΡΠ΅Π½ΠΊΠ΅ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ ΠΎΠΆΠΈΠ΄Π°Π΅ΠΌΠΎΠΉ ΠΏΠΎΠ»ΡΠ·Ρ ΠΊ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠΌΡ ΡΠΈΡΠΊΡ ΠΏΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΡΠ°ΡΠΌΠ°ΠΊΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ Ρ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
Π΄ΠΈΠΊΡΡΠ΅Ρ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ Π΄Π°Π½Π½ΠΎΠ³ΠΎ Π½Π°ΡΡΠ½ΠΎΠ³ΠΎ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡ
ΠΠΎΠ²ΡΠ΅ Π°Π½ΡΠΈΠΊΠΎΠ½Π²ΡΠ»ΡΡΠ°Π½ΡΡ: ΠΏΡΠΎΠ±Π»Π΅ΠΌΡ Π²Π·Π°ΠΈΠΌΠΎΠ·Π°ΠΌΠ΅Π½ΡΠ΅ΠΌΠΎΡΡΠΈ ΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π²ΠΎΡΠΏΡΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½Π½ΡΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅
This article looks into interchangeability and therapeutic equivalence of innovator and generic anticonvulsants β the first-generation and new antiepileptic drugs (AEDs). The results of a number of clinical trials assessing therapeutic equivalence of generic AEDs support the opinion that these medicines could only be substituted provided an ultra-cautious approach is used, even if the case involves only one International Nonproprietary Name, including, but not limited to different dosage forms of one and the same product. The aim of the study was to analyse factors leading to incorrect assessment of therapeutic equivalence of new and generic anticonvulsant drugs, and to improve methodological approaches to conducting clinical trials of these products. The paper cites data from Russian and foreign sources which state that the substitution of AEDs in some patients in full remission may result in adverse reactions or relapse of seizures. The analysis of the experience of scientific, expert, and regulatory institutions made it possible to develop a course of actions to be used when substituting AEDs and conducting clinical trials that assess therapeutic equivalence of new and generic anticonvulsants. The proposed methodology will help minimise potential health risks brought about by various factors that result in incorrect assessment of AEDs therapeutic equivalence and interchangeability.Π‘ΡΠ°ΡΡΡ ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π° ΠΏΡΠΎΠ±Π»Π΅ΠΌΠ΅ Π²Π·Π°ΠΈΠΌΠΎΠ·Π°ΠΌΠ΅Π½ΡΠ΅ΠΌΠΎΡΡΠΈ ΠΈ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΊΠ²ΠΈΠ²Π°Π»Π΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΡ
ΠΈ Π²ΠΎΡΠΏΡΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½Π½ΡΡ
Π°Π½ΡΠΈΠΊΠΎΠ½Π²ΡΠ»ΡΡΠ°Π½ΡΠΎΠ² β ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠΏΠΈΠ»Π΅ΠΏΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² (ΠΠΠ) ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ ΠΏΠΎΠΊΠΎΠ»Π΅Π½ΠΈΡ ΠΈ Π½ΠΎΠ²ΡΡ
. Π ΡΡΠ΄Π΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΊΠ²ΠΈΠ²Π°Π»Π΅Π½ΡΠ½ΠΎΡΡΠΈ Π²ΠΎΡΠΏΡΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½Π½ΡΡ
ΠΠΠ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°Π΅ΡΡΡ Π²ΡΠ²ΠΎΠ΄ ΠΎ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΠΈ ΠΊΡΠ°ΠΉΠ½Π΅ ΠΎΡΡΠΎΡΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Π° ΠΊ ΠΎΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΈΡ
Π·Π°ΠΌΠ΅Π½Ρ Π΄Π°ΠΆΠ΅ Π² ΡΠ°ΠΌΠΊΠ°Ρ
ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΌΠ΅ΠΆΠ΄ΡΠ½Π°ΡΠΎΠ΄Π½ΠΎΠ³ΠΎ Π½Π΅ΠΏΠ°ΡΠ΅Π½ΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π½Π°ΠΈΠΌΠ΅Π½ΠΎΠ²Π°Π½ΠΈΡ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΠΌΠ΅ΠΆΠ΄Ρ ΡΠ°Π·Π½ΡΠΌΠΈ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠΌΠΈ ΡΠΎΡΠΌΠ°ΠΌΠΈ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°. Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β Π°Π½Π°Π»ΠΈΠ· ΡΠ°ΠΊΡΠΎΡΠΎΠ², ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠΈΡ
ΠΊ Π½Π΅ΠΏΡΠ°Π²ΠΈΠ»ΡΠ½ΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠ΅ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΊΠ²ΠΈΠ²Π°Π»Π΅Π½ΡΠ½ΠΎΡΡΠΈ Π½ΠΎΠ²ΡΡ
ΠΈ Π²ΠΎΡΠΏΡΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½Π½ΡΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΡΡΠ΄ΠΎΡΠΎΠΆΠ½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΈ ΡΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ² ΠΊ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΡΡΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ². ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ Π΄Π°Π½Π½ΡΠ΅ ΠΈΠ· ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΈ Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΡ
ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ², Π² ΠΊΠΎΡΠΎΡΡΡ
ΠΎΡΠΌΠ΅ΡΠ°Π΅ΡΡΡ, ΡΡΠΎ Π·Π°ΠΌΠ΅Π½Π° ΠΠΠ Ρ ΠΎΡΠ΄Π΅Π»ΡΠ½ΡΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΏΠΎΠ»Π½ΠΎΠΉ ΡΠ΅ΠΌΠΈΡΡΠΈΠ΅ΠΉ ΠΌΠΎΠΆΠ΅Ρ ΠΏΡΠΈΠ²Π΅ΡΡΠΈ ΠΊ ΡΠ°Π·Π²ΠΈΡΠΈΡ Π½Π΅ΠΆΠ΅Π»Π°ΡΠ΅Π»ΡΠ½ΡΡ
ΡΠ΅Π°ΠΊΡΠΈΠΉ ΠΈΠ»ΠΈ Π²ΠΎΠ·ΠΎΠ±Π½ΠΎΠ²Π»Π΅Π½ΠΈΡ ΡΡΠ΄ΠΎΡΠΎΠΆΠ½ΡΡ
ΠΏΡΠΈΠΏΠ°Π΄ΠΊΠΎΠ². ΠΠ° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΠΈΠ·ΡΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΎΠΏΡΡΠ° ΡΠ°Π±ΠΎΡΡ Π½Π°ΡΡΠ½ΡΡ
, ΡΠΊΡΠΏΠ΅ΡΡΠ½ΡΡ
ΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΡ
ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠΉ Π°Π²ΡΠΎΡΡ ΠΏΡΠ΅Π΄Π»Π°Π³Π°ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡ ΠΌΠ΅ΡΠΎΠΏΡΠΈΡΡΠΈΠΉ ΠΏΡΠΈ Π·Π°ΠΌΠ΅Π½Π΅ ΠΠΠ ΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΊΠ²ΠΈΠ²Π°Π»Π΅Π½ΡΠ½ΠΎΡΡΠΈ Π½ΠΎΠ²ΡΡ
ΠΈ Π²ΠΎΡΠΏΡΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½Π½ΡΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΡΡΠ΄ΠΎΡΠΎΠΆΠ½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ². ΠΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½ΠΎΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ»ΠΎΠ³ΠΈΠΈ Π±ΡΠ΄Π΅Ρ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΠΎΠ²Π°ΡΡ ΠΌΠΈΠ½ΠΈΠΌΠΈΠ·Π°ΡΠΈΠΈ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΡ
ΡΠΈΡΠΊΠΎΠ² Π΄Π»Ρ Π·Π΄ΠΎΡΠΎΠ²ΡΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΡ
ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΡΠ°ΠΊΡΠΎΡΠ°ΠΌΠΈ, ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΠΈΠΌΠΈ ΠΊ Π½Π΅ΠΏΡΠ°Π²ΠΈΠ»ΡΠ½ΠΎΠΉ ΠΎΡΠ΅Π½ΠΊΠ΅ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΊΠ²ΠΈΠ²Π°Π»Π΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΠΠ ΠΈ ΠΈΡ
Π²Π·Π°ΠΈΠΌΠΎΠ·Π°ΠΌΠ΅Π½ΡΠ΅ΠΌΠΎΡΡΠΈ