[Morphological aspects of protective influence of carbonic enterosorbent and granulocyte colony stimulating factor on small intestine in case of Melphalan administration]

Background. High toxicity of anti-cancer drugs limits the efficacy of the treatment of malignant tumors. The most frequent side effects are the injury of highly proliferative cell and tissues: hematologic and gastrointestinal toxicity. Our previous study showed high myeloprotective activity of combination of carbonic enterosorbent and granulocyte colony stimulating factor. The objective of this investigation is to study the morphologic characteristic of small intestine in case of melphalan injection and pharmacocorrection with carbonic granulated enterosorbent C2 and filgrastim. Methods. Histologic structure of jejunum of healthy male inbred rats, after the melphalan injection (4 mg/kg) and its correction with enterosorption and filgrastim apart, and in combination was investigated. Results. Cytostatic melphalan caused the dilation of microcirculatory vessels and expressed perivasal edema leading to enlargement of intestinal villi. It was revealed a large amount of lymphocytes and histiocytes in stroma and signs of increasing secretory activity of glandular cells. Dystrophic changes of the epithelium were seen. The enteral sorptive therapy showed prominent improvement of morphologic characteristic of jejunum. But sighs of increased mucus production were still seen. The granulocyte colony stimulating factor has no effects on small intestine structures. The combination of carbonic enterosorbent and filgrastim improved the histologic picture maximally. Conclusion. Combination of enterosorption and granulocyte colony stimulating factor is a prospective approach to diminish the gastrointestinal toxicity of cytostatic therapy. Citation: Shevchuk OO. [Morphological aspects of protective influence of carbonic enterosorbent and granulocyte colony stimulating factor on small intestine in case of Melphalan administration]. Morphologia. 2015;9(3):117-21. Ukrainian

МЕТОДОЛОГІЧНІ АСПЕКТИ ЗАСТОСУВАННЯ РИНКОВОГО ПІДХОДУ ДО ОЦІНЮВАННЯ ВАРТОСТІ СТРАХОВИХ КОМПАНІЙ

Current changes in the structure of the insurance marketplace objectively determine the need for deep scientific analysis of the insurance business as the object of assessment. That is why our research aims at defining market value of insurance companies based on market approach with the analysis of strengths and weaknesses of this approach and systematization of internal and external factors that determine the insurer's value. We have found that market or comparative approach to company valuation is a combination of valuation methods based on a comparison of the object of assessment with the similar objects for which there is information about transaction prices or about market value of shares.The approach provides using three major methods, depending on the purpose, object and specific conditions of evaluation such as capital markets method, deals method, and sectoral factors method.To improve the process of evaluating the cost of the insurance company on the basis of sectoral factors method we suggest methodology for calculating the sectoral factor, which in addition to ranking companies by gross premiums, considering other equally important parameters that determine the attractiveness of insurance companies in terms of clients and investors: debt load, liquidity of insurance company, the level of payments, increase in premiums, increase in equity of insurer, membership in the international financial group (international insurance company), the level of reinsurance, credit rating of the insurance company from the international or domestic rating agency, the factor of financial stability (autonomy) of the insurer, its customer base. Thus, the methodology of sectoral factors estimation proposed in this study allows considering both external and internal factors that determine the value of the company and the specific features of insurance, which significantly improve the quality and reliability index of value, estimated by the market approach.Определена рыночная стоимость страховых компаний на основе использования рыночного подхода с анализом сильных и слабых сторон данного подхода, а также с систематизацией внутренних и внешних факторов, определяющих стоимость страховщика. Предложена методика расчета отраслевого коэффициента на основе определения привлекательности страховой компании для клиентов и инвесторов, которая учитывает факторы стоимости и особенности страховой деятельности, что позволяет существенно повысить качество и достоверность показателя стоимости, оцененного по рыночному подходу.Визначено ринкову вартість страхових компаній на основі використання ринкового підходу з аналізом сильних та слабких сторін цього підходу, а також із систематизацією внутрішніх і зовнішніх факторів, що визначають вартість страховика. Запропонована методика розрахунку галузевого коефіцієнта на основі визначення привабливості страхової компанії для клієнтів та інвесторів, яка враховує фактори вартості та особливості страхової діяльності, що дає змогу істотно підвищити якість та достовірність показника вартості, оціненого за ринковим підходом

Theoretical ground for adsorptive therapy of anthracyclines cardiotoxicity

Anthracyclines play an important role in treatment of variety types of cancer due to their high effectiveness and broad spectrum of activity. However, a major limitation of their use is the dose-limiting cardiotoxicity. The inability to predict and prevent anthracycline cardiotoxicity is in part due to the fact that the molecular and cellular mechanisms remain controversial and incompletely understood. This review focuses on the biochemical basis of the anthracyclines toxic cardiac effects and pharmacological measures to their treatment and preventing. We describe the theoretical substantiation of the enterosorption abilities for diminishing of cardiac damage

Key links in pathogenesis of respiratory failure in COVID-19 and pharmacological correction

Summary. COVID-19 pandemic became a game-changer player in the whole world. The severe course of disease manifests with clinical signs of viral pneumonia with an advanced respiratory failure, which can later lead to the development of acute respiratory distress syndrome (ARDS) and fatal consequences. Correct understanding of the key pathophysiological determinants of complications and hypoxemia will contribute to the most rational pharmacotherapy. The aim of the study – to analyze and systematize data on the pathogenesis of ARDS in coronavirus disease and its pharmacological correction. Understanding the key links will make possible not only to identify certain aspects of the treatment, but also to prevent the development of complications. Materials and Methods. Publications of foreign and Ukrainian specialists were analyzed, including databases Medscape/PubMed. Results. An analysis of the key links in the pathogenesis of ARDS, induced by C|OVID-19, the role of the cytokine storm in the progression of the disease and development of arterial hypoxemia and respiratory failure was carried out. An overview of the development and "evolution" of approaches to the treatment of the disease was conducted, starting from attempts to use chloroquine derivatives at the beginning of pandemic to etiotropic treatment with antiviral drugs (such as remdesivir, the combination of lopinavir/ritonavir and paxlovid); biosimilars – monoclonal antibodies and their combinations; prevention and treatment of thrombosis and microthrombosis, which may develop as a result of endothelial dysfunction in such patients, especially in the presence of comorbid pathology (for example, hypertension, diabetes mellitus, obesity). The latest recommendations and American and European protocols for the treatment of coronavirus disease are summarized. Conclusions. The review of the most popular and available medicines and pharmacotherapy for COVID 19 was performed. It indicates the necessity and rationality of finding new, more efficient and less toxic drugs to fight the infection and its complication

Enterosorption as a method to decrease the systemic toxicity of cisplatin

A perspective adsorptive method to minimize systemic toxic effects of chemotherapy is enterosorption (ES). However, the capabilities of this method are far from being completely studied. The question remains opened — should ES be initiated in the first hours on completing cytostatic infusion without the risk of their anticancer activity to be decreased. Aim: to analyze ES influence on anticancer activity and toxic reactions of cisplatin (CP) upon the use of carbon enterosorbent in 1 h after intravenous administration of cytostatic. Methods: CP at the dose of 1 mg/kg body weigh (BW) was administered to Guerin carcinoma-bearing rats each second day for two weeks. Enterosorbents on the basis of highly activated carbon fibers were administered by per os daily 1 h after CP injection. 3 days after the last CP administration the rats were weighted and blood under ether narcosis has been taken for biochemical examination. Tumors and innate organs were isolated, weighted, and fixed in 4% buffered formalin for morphologic examination. Results: In rats administered with CP at the background of ES, BW loss was in 1.6 times lower than in animals after CP session. Relative kidney weight in CP-treated rats was 33.9% higher than in normal ones (p ≤ 0.05). No significant differences were detected between relative kidney weights in the CP + ES-treated and intact animals. Introduction of ES allowed prevent an 30% increase of creatinin content observed in blood plasma after CP treatment (р ≤ 0.05). Urea content was 1.7 times lower in blood plasma of CP + ES-treated rats than after CP treatment. CP caused significant toxic injuries in kidneys, liver, and spleen tissues. Morphologic structure of organs in rats treated with CP at the background of ES was affected at much lower degree. In tumors, large areas of newly formed connective tissue and blood vessels have been fixed after the CP+ES action instead of large necrotic area observed after CP treatment. ES caused insignificant suppression of Guerin carcinoma growth and had additional impact to inhibitory action of CP. Conclusion: Active carbon enterosorbents which are administrated just 1 h after CP administration possesses detoxicating potential sufficient for significant elimination of toxic effect of the cytostatic at the background of complete preservation of its antitumor activity

Prevention of myelosuppression by combined treatment with enterosorbent and granulocyte colony-stimulating factor

Hematotoxicity and its complication are the prominent limiting factors for rational treatment of malignancies. Granulocyte colony-stimulating factor (G-CSF) is used to increase granulocyte production. It has been shown previously that enterosorption causes prominent myeloprotective activity also. Still, no trial was performed to combine both of them. Aim: To study the influence of combination of enterosorption and pharmaceutical analogue of naturally occurring G-CSF (filgrastim) on bone marrow protection and the growth of grafted tumor in a case of injection of melphalan (Mel). Materials and Methods: Mel injections were used for promotion of bone marrow suppression in rats. Carbon granulated enterosorbent C2 (IEPOR) was used for providing of enteral sorption detoxifying therapy. Filgrastim was used to increase white blood cells (WBC) count. Results: The simultaneous usage of enterosorption and filgrastim had maximum effectiveness for restoring of all types of blood cells. WBC count was higher by 138.3% compared with the Mel group. The increase of platelets count by 98.5% was also observed. In the group (Mel + C2 + filgrastim) the absolute neutrophils count was twofold higher, in comparison with rats of Mel group. Conclusion: Simultaneous admi­nistration of G-CSF-analogue and carbonic enterosorbent C2 is a perspective approach for bone marrow protection, when the cytostatic drug melphalan is used. Such combination demonstrates prominent positive impact on restoring of all types of blood cells and had no influence on the antitumor efficacy. Key Words: myelotoxicity, melphalan, enterosorption, granulocyte colony-stimulating factor

Перший досвід застосування робот-асистованої хірургії в дитячому віці в Україні

У сучасному світі все більшої популярності набувають високотехнологічні оперативні втручання, серед них - роботична хірургія, зокрема в дитячому віці. Мета - описати перший досвід застосування роботичного обладнання в мініінвазивному лікуванні дітей з хірургічною патологією в одній з найбільших регіональних клінік України. Матеріали та методи. Прооперовано 13 дітей з різними нозологічними одиницями та різного віку (наймолодша дитина - 6 років). Результати. Під час аналізу результатів встановлено, що роботична хірургія має ряд переваг і може ширше застосовуватись у дитячій хірургії. Охарактеризовано необхідні умови для роботичних операцій. Висновки. Роботична хірургія має ряд переваг і може ширше застосовуватись у дитячій хірургії. У роботичній хірургії може розширюватися діапазон оперативних втручань та зменшуватися вік пацієнтів, які кваліфікуються до роботичних операцій. При інсталяції обладнання слід враховувати багатовекторність клініки. Дослідження виконано відповідно до принципів Гельсінської декларації. Протокол дослідження ухвалено Локальним етичним комітетом зазначеної в роботі установи. На проведення досліджень отримано інформовану згоду пацієнтів. Автори заявляють про відсутність конфлікту інтересів

Enterosorption combined with granulocyte colony stimulating factor decreases melphalan gonadal toxicity

Today due to improvements in cancer treatment there is an increasing number of long-term cancer survivors, many of whom suffer from infertility caused by malignancy itself and chemo- or radiotherapy. Also, anticancer therapy may cause myelosuppression. Presently granulocyte colony stimulating factor (G-CSF) is used for prevention and treatment of myelosuppression. Another treatment option used to decrease intoxication and ameliorate side effects of cancer therapy is sorption technology. The aim of our investigation was to study the efficiency of combined use of enterosorption and G-CSF to decrease gonadal toxicity of chemotherapy. Materials and Methods: Melphalan (L-PAM) injected i.v. at a single dose of 4 mg/kg to white inbred rats was used as gonadotoxic and myelosuppressing agent. Carbon enterosorbent C2 was administered by intragastric route as a suspension in saline at a dose of 5 ml per 1 kg of rats’ body weight (or 900 mg/kg of the dry mass of enterosorbent) daily for 3 days before and for 7 days after L-PAM injection. G-CSF was injected once a day for 4 days starting from the next day after L-PAM administration at a dose of 50 µg/kg. Histological preparations of testicular tissues were examined by light microscopy. Results: Our findings have shown that melphalan caused marked damage of testicular tissues and seminiferous, especially spermatogenic epithelium. The most expressed protection of the histological structure of testes was observed when enterosorbent and G-CSF were used in combination. Conclusion: Gonadal toxicity of chemotherapy could be efficiently decreased by the combined use of enterosorption and G-CSF

The influence of enterosorption on some haematological and biochemical indices of the normal rats after single injection of melphalan

Aim: One of the most prominent side effects of intensive cancer chemotherapy is bone marrow suppression which is an independent negative prognostic factor for the time to tumor progression. The aim of the study was to evaluate the myeloprotective possibilities of carbon enterosorbents in the case of usage of alkilating drug melphalan (L-PAM). Materials and Methods: L-PAM was injected intravenously to healthy inbred rats to cause the myelosuppression. 3 days before and 7 days after this, suspension of two types of carbon granulated enterosorbents were administered per os one time per day. On 8th day after L-PAM injection, the rats were weighted and blood and liver tissue were taken under Ketamine general anesthesia for biochemical examination. Peripheral blood smears were made also. Results: Melphalan at a dose of 3 mg/kg causes expressed myelotoxic reaction: leucopenia, decre­asing of erythrocytes, hemoglobin and platelets counts. Even on 8th day after single injection of this cytostatic we can detect expressed signs of oxidative stress like increasing of hydroperoxides, TBA-reactive substances, and decreasing of activity and level of main endogenic antioxidants — superoxide dismutase (SOD), catalase and reduced glutathione. L-PAM causes also the violation of kidney function such as increase of urea and creatinine level; and rising of endogenic intoxication with elevation of middle mass molecules level. In a dose of 3 mg/kg melphalan has no negative influence on liver function on 8th day of experiment. Enterosorption with carbon enterosorbents C1 (bulk density γ = 0.28 g/cm³, granules diameter 0.15–0.25 mm, BET pore surface 1719 m²/g, therapeutic dosage 1400 mg/kg) and C2 (bulk density γ = 0.18 g/cm³, granules diameter 0.15–0.25 mm, BET pore surface 2162 m²/g, therapeutic dosage 900 mg/kg) diminishes and mitigates negative side effects caused by single intravenous injection of melphalan. Carbon enterosorbent C2 have rather more expressed positive effect than C1 for practically all indices. The most important curative effect due to C2 administration is prominent myeloprotection of bone marrow of experimental animals. Conclusion: Carbon enterosorbent C2 is promising and perspective sorbent for prophylaxis and treatment of side effects of cytostatic chemotherapy including myelotoxicity, mucositis, kidney injuries, gonadotoxicity, etc. Key Words: L-PAM, myelosuppression, oxidative stress, carbon enterosorbents

Методы оценки рисков в страховой деятельности

Проаналізовано та систематизовано сучасні методи оцінювання ризику у страховій діяльності. Розглянуто деякі методи аналізу невизначеностей як інструментарій середньострокового прогнозування та планування діяльності страхових компаній. Виокремлено статистичні та аналітичні методи, методи експертних оцінок, що застосовуються у разі відсутності чи недостатності статистичної бази, а також деякі специфічні методи на перетині статистичних та експертних. Ефективність висновків та формування подальшої стратегії компанії безпосередньо залежить від правильності вибору методу аналізу та оцінки ризику і від якості сформованої статистичної бази.Some modern methods of risk assessment in insurance activities are analyzed and systematized. Some certain methods of uncertainty analysis as a tool of medium-term forecasting and planning of the insurance companies activities are considered. Statistical and analytical methods, expert evaluation methods, used in the case of the lack or insufficiency of the statistical base, as well as some specific methods at the intersection of statistics and expert methods are highlighted. The efficiency of the conclusions and company's strategy formation depends directly on the correctness of the choice of a risk evaluation method and the quality of the existing statistical framework.Проанализированы и систематизированы современные методы оценки риска в страховой деятельности. Рассмотрены отдельные методы анализа неопределенностей как инструментарий среднесрочного прогнозирования и планирования деятельности страховых компаний. Выделены статистические и аналитические методы, методы экспертных оценок, применяемые в случае отсутствия или недостаточности статистической базы, а также некоторые специфические методы на пересечении статистических и экспертных. Эффективность выводов и формирования дальнейшей стратегии компании напрямую зависит от правильности выбора метода анализа и оценки риска, а также от качества сформированной статистической базы