The derivative of 1,3-oxazole-4-yl-phosphonic acid (OVP-1) has the vasodilatory activity and is studied as a potential antihypertensive agent. The toxicological assessment plays an important role in the preclinical study of new drugs.Aim. To study the acute toxicity of OVP-1 in intraperitoneal administration and determine its average lethal dose. Materials and methods. The intraperitoneal route of administration was chosen as it provides the systemic action of drugs. The experiment was conducted on female and male of white non-linear mice. Five experimental groups of animals corresponded to such dose levels of OVP-1 as 1000 mg/kg, 3000 mg/kg, 3500 mg/kg, 4000 mg/kg, and 4500 mg/kg. The solution of 1,3-oxazole-4-yl-phosphonic acid derivative and the blank solution (the mixture of Tween-80 and water for injection in the ratio of 1 : 10) was injected once in the abdominal cavity of mice. They were monitored for their mortality, behavior, and clinical characteristics over the following 14 days. LD 50 of OVP-1 was determined by the number of dead animals before autopsy.Results and discussion. As a result of the experiment the peculiarities of the toxic effect of 1,3-oxazole-4-ylphosphonic acid derivative on the organism of the experimental mice have been studied. Based on clinical observations there were no changes in the behavior and appearance of mice for 14 days. However, taking into account the rare cases of tachypnea, piloerection and catalepsy, it can be assumed that OVP-1 in toxic doses can affect the central nervous system, the autonomic system, and there is a probability of occurrence of cardio-pulmonary insufficiency.Conclusions. It has been determined that LD 50 of OVP-1 derivative in intraperitoneal administration to mice of both sexes is 3350.67 ± 54.62 mg/kg and belongs to the toxicity class VI -relatively harmless compounds, which makes this compound promising for further preclinical pharmacological studies. Дослідження гострої токсичності похідного 1,3-оксазол-4-іл-фосфонової кислоти при внутрішньоочеревинному введенніISSN 2415-8844 (Online) ISSN 1562-7241 (Print) И. В. Ниженковская, Е. В. Седько, А. В. Головченко, О. И. Головченко Исследование острой токсичности производного 1,3-оксазол-4-ил-фосфоновой кислоты при внутрибрюшинном введенииПроизводное 1,3-оксазол-4-ил-фосфоновой кислоты (ОВП-1) имеет вазодилатирующую активность и изучается в качестве потенциального антигипертензивного средства. Важную роль в доклиническом изучении новых лекарственных средств имеет их токсикологическая оценка.Цель работы -исследовать острую токсичность ОВП-1 при внутрибрюшинном введении и определить его среднелетальную дозу.Материалы и методы. Внутрибрюшинный путь введения был выбран как тот, который обеспечивает системное действие лекарственных средств. Эксперимент проводили на самках и самцах белых нелинейных мышей. 5 подопытных групп животных соответствовали уровням доз ОВП-1 -1000 мг/кг, 3000 мг/кг, 3500 мг/кг, 4000 мг/кг, 4500 мг/кг. Введение раствора производного 1,3-оксазол-4-ил-фосфоновой кислоты и контрольного р...

The purpose of this study was to identify what effect the entrepreneurship technology-driven environment has on the selfdirected learning skills of graduate pharmaceutists. This was quasiexperimental research using quantitative and qualitative instruments to collect and process data. The graduate students majoring in Pharmacy were sampled to form the experimental and control groups. The selfdirected learning skills scale, the integrated achievement test, and a retained knowledge test in Chemistry, the entrepreneurial potential selfassessment questionnaire, the questionnaire on computer literacy, and a semi-structured interview were the measurement instruments for the study. The IBM SPSS Statistics software and effect size calculator for t-test were used to process statistical data yielded from measurements. The results suggested that a technology-mediated learning environment combining the professionalism-related online course with an online collaboration-based entrepreneurship project fosters self-directed learning skills bringing substantial educational and professional benefits like developed entrepreneurial skills, computer skills, and better academic performance to the students majoring in Pharmacy. Measurements results of the variables showed that the participants of the experimental group who received project-based online training in entrepreneurship showed ≈20% improvement in self-directed learning skills, entrepreneurial potential, computer literacy, and academic achievements. The intervention model was also perceived positively by the participants. It is recommended that the teachers were trained in Marketing before the delivery of the course.

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Анотація. У статті розглянуто взаємозалежність дієвості механізму макроекономічного регулювання та зростання національної економіки, що підтверджується результатами регулювання, до яких можна віднести: стійке підвищення макроекономічних індикаторів, раціональне розпорядження фінансовими ресурсами, зростання добробуту населення, формування ресурсо-ефективної економіки та зміцнення економічного партнерства тощо. Збалансований взаємозв'язок між всіма ланками та сегментами механізму макроекономічного регулювання забезпечує високу його функціональність та адаптивність до трансформаційних змін, що є важливою умовою сучасних концепцій соціально-економічного розвитку. Таким чином, суттєві зміни в інституційному забезпечені стійкого зростання національної економіки в адаптивних умовах з урахуванням інноваційних концепцій впливають на удосконалення механізмів державного регулювання соціально-економічного розвитку. Вибір оптимальної моделі макроекономічного регулювання стійкого зростання національної економіки супроводжується визначенням стратегічної мети та відповідних завдань. Формування дієвого механізму макроекономічного регулювання зростанням базується на методологічних підходах та принципах, певним чином залежить від наявності соціально-економічних диспропорцій, а також потенціальних можливостей в їх подоланні. Ключові слова: механізм макроекономічного зростання, стійке зростання національної економіки, адаптивні умови, стратегія державного регулювання, якість економічного розвитку. Серія: Міжнародні економічні відносини та світове господарство ♦ MECHANISM OF MACROECONOMIC REGULATION OF SUSTAINABLE GROWTH OF THE NATIONAL ECONOMY IN ADAPTIVE CONDITIONS Summary. The article considers the interdependence of the mechanism of macroeconomic regulation and growth of the national economy, which is confirmed by the results of regulation, which include: steady increase of macroeconomic indicators, rational use of financial resources, growth of welfare, formation of resource-efficient economy and strengthening of economic partnership. A balanced relationship between all parts and segments of the mechanism of macroeconomic regulation ensures its high functionality and adaptability to transformational change, which is an important condition for modern concepts of socioeconomic development. Thus, significant changes in the institutional support for sustainable growth of the national economy in adaptive conditions, taking into account innovative concepts, affect the improvement of mechanisms of state regulation of socioeconomic development. The choice of the optimal model of macroeconomic regulation of sustainable growth of the national economy is accompanied by the definition of strategic goals and relevant objectives. The formation of an effective mechanism of macroeconomic regulation of growth is based on methodological approaches and principles, to some extent depends on the presence of socioeconomic imbalances, as well as potential opportunities to overcome them.

One of the promising chemical groups for the development of new antihypertensive medicines, the action of which is associated with the inhibition of phosphodiesterase III (PDE3) activity, are phosphorylated oxazole derivatives (OVPs). Purpose: To prove experimentally the presence of the OVPs antihypertensive effect associated with decreasing of PDE activity and to justify its molecular mechanism. Methods: An experimental study of the effect of OVPs on phosphodiesterase activity was performed on Wistar rats. Determination of PDE activity was performed by fluorimetric method using umbelliferon in blood serum and organs. The docking method was used to investigate the potential molecular mechanisms of the antihypertensive action of OVPs with PDE3. Results: The introduction of OVP-1 50 mg/kg, as a leader compound, led to the restoration of PDE activity in the aorta, heart and serum of rats with hypertension to the values observed in the intact group. This may indicate the possibility of the development of vasodilating action of OVPs by the influence of the latter on the increase in cGMP synthesis due to inhibition of PDE activity. The calculated results of molecular docking of ligands OVPs to the active site of PDE3 showed that all test compounds have a common type of complexation due to phosphonate groups, piperidine rings, side and terminal phenyl and methylphenyl groups. Conclusion: The analysis of the obtained results both in vivo and in silico showed that phosphorylated oxazole derivatives represent a new platform for further studies as phosphodiesterase III inhibitors with antihypertensive activity.