ABSTRACT
The aim: A comprehensive analysis of anxiety as an emotional state and pathopsychological symptom in the situation of a massive humanitarian catastrophe in wartime
Materials and methods: A systematic search was conducted up to April 2022 in the following databases: Google Scholar, PubMed, DOAJ, and CORE. Three reviewers independently assessed full-text articles according to a predefined aim. We used a quantitative and qualitative approach to infer. The range of mental reactions to the intensive stress with a pooled prevalence of anxiety was estimated. Anxiety as an independent structural psychological phenomenon or incorporated into more complicated mental states, including mental disorders, was assessed.
Conclusions: The anxiety features as an expected mental reaction to the threatening environment are established, the analysis of anxiety development trajectories was shown, and the basic principles of psychological care in anxiety states are considered. The criteria of pathological anxiety, the characteristic of the anxiety symptom as a structural element of psychiatric diseases, and the modern methods of treatment of anxiety disorders are presented. Many specialists in the different areas work with anxious people and patients with anxiety disorders in the Ukrainian current situation, so it was concluded that understanding and being aware of the differentiation of anxiety states will improve psychological care and, if necessary, will lead to providing of a full spectrum of specialized medical care

UDC: 61:612.4:615.9.616.4:616-09

Snakebite envenoming is a common but neglected public health problem worldwide, especially in tropical countries. Annual mortality as a result of snakebites exceeds 138,000. It is believed that this problem is underestimated, and in many countries, individual cases of bites are not subject to proper fixation. The purpose of the study is the analytical and quantitative assessment of the structural components of the rats' adrenal glands under exposure to the venom of Vipers Vipera berus berus and Vipera berus nikolskii. Experimental studies were carried out on white, non-linear male rats. Vipera berus berus and Vipera berus nikolskii viper venom were obtained from V. N. Karazin Kharkiv National University. The freeze-dried native venom was stored at
-20 °C and dissolved in saline immediately before the experiment. The animals were divided into three groups (control and 2 experimental groups) of 10 individuals each. Experimental rats were injected intraperitoneally in a physiological solution with a semi-lethal dose (LD50) (1.576 mg/g-1) of Vipera berus berus and Vipera berus nikolskii venoms. Animals of the control group were injected intraperitoneally with only a physiological solution. Rats were removed from the experiment 24 hours after exposure to the poison and anesthetised by cervical dislocation. Statistical analysis of the area
of the microcirculatory channel and the nuclear-cytoplasmic index was performed using Fiji: ImageJ program and processed in Excel. Administration of the venom of the vipers Vipera berus berus and Vipera berus nikolskii to rats was accompanied by a significant increase in the area of the microcirculatory bed relative to the control group (2.9 times for Vipera berus berus and 6.5 times for Vipera berus nikolskii). Exposure to Vipera berus berus viper venom was associated with a significant decrease in the nuclearcytoplasmic index in rats of the experimental group compared to the control group (13 % and 42 %, respectively), which is evidence of a decrease in the area of the nuclei of endocrinocytes of the adrenal cortex. This indicator in rats under the administration of Vipera berus nikolskii venom was even lower and amounted to 12 %. According to the statistical analysis of the quantitative assessment of the state of the cortical substance of the adrenal glands, it is worth noting the similar effect of the poisons of both types of snakes at the cellular level. At the same time, at the tissue level, the effect of Vipera berus nikolskii venom is more pronounced than that of Vipera berus berus - this is evidenced by the higher degree of disruption of the structure of the hemomicrocirculatory channel in the adrenal cortex of animals from the group that was affected by this venom. It led to an increase in the area of vessels due to their expansion and ruptures of their walls and haemorrhages into the surrounding parenchyma and stroma.

Over the last decade, there has been an increase in illegal drug use and uncontrolled opioid abuse in patients with chronic pain, which is associated with unintentional trauma and is a major risk factor for tolerance and withdrawal, leading to overdose and death [1-5]. The attention of scientists in various fields of medicine is focused on the study of changes in organs and systems under the influence of drugs, in particular, both in clinical and experimental
areas [6-9]. In clinical studies it is indicated that when exposed to opioids there are signs of immunosuppression, which cause an increased risk of infectious diseases and the development of inflammation [5, 10, 11]. Toxic effects of drugs are manifested in all organs and systems, which
may have an indirect or direct effect on the organs of the oral cavity [6, 12-15]. The question of the role of bacterial flora in the etiology and initiation of periodontal disease is certainly actively studied as the improvement of microbiological methods and the accumulation of research results [16-19]. Today,
one of the main hypotheses remains that dental plaque microorganisms are a determining factor in the development and progression of the inflammatory process in the periodontium, which provoke the inflammatory process and directly affect the microbial status of the oral cavity [20- 23].There is also evidence that the role of microorganisms in the development of periodontitis is unclear, although some bacterial pathogens alone or as part of microbial groups may be particularly important [24]. Therefore, in order to prevent the development of periodontal disease and the occurrence of infectious foci in the oral cavity caused by bacterial biopellicle, it is important to determine the etiology and pathogenesis of this pathology in experimental animal models in order to further extrapolate these data to the clinic [25]. However, the relationship between the species and quantitative composition of the microbiota of tooth surface in the gingival margin and the development and progression of inflammation in the gingival mucosa under action of the opioid are controversial and needs further study using modern methods of microbiological research in the experiment.

The research aimed to conduct a comparative analysis of the academic components of Pharmacy education programs of higher education institutions in Ukraine and EU countries and to study their development experience. The research objects were the Pharmacy education programs presented at the official websites of higher education institutions of Ukraine, Poland, Italy, Sweden, and Germany. Analytical-comparative, content, systematic, meta-analysis, logical, decomposition, and modeling research methods were used. There were established similar and different academic elements relevant to the title, structure, content, and workload hours in higher education institutions of Ukraine and EU countries. It determined the criteria of the originality and specific direction of the Pharmacy education programs, which indicates the peculiarities of specialists' training of a certain degree level and qualification. The importance of the vector of European integration processes in higher education institutions in Ukraine concerning the modeling and development of students’ learning process by the Pharmacy specialty has been proven. The research results can be a guide for making changes and annexes to the structure and content of the Pharmacy education programs in higher education institutions of Ukraine for maximal convergence and harmonization of the education system with the EU countries within the framework of the Bologna Agreement, intending to create a single European area of higher education.

Keywords: Pharmacy education, Curriculum, Education programs, Academic component, Learning process, Higher education institution

УДК: 547.792.9+547.859+547.874+547.789.6):615.074:615.211-099

Перспективними анальгетиками, що водночас виявляють протизапальні властивості, є похідні 5,7-діацил-3-Н(алкіл)-6-арил-5Н-[1,2,4]тріазоло[3,4-b][1,3,4]тіадіазину.

Мета. Оцінити дозозалежність знеболювального ефекту сполуки IFT_247, участь опіоїдергічної складової в механізмі дії цієї сполуки, її вплив на поведінкові реакції у тесті відкритого поля та визначити гостру токсичність.

Матеріали і методи. Об'єктом дослідження обрано сполуку IFT_247. У дослідженні використано 80 білих безпородних мишей самців. Дослідження соматичного болю проводили з використанням тесту "Гаряча пластина". Як конкурентний блокатор опіоїдних рецепторів використовували налоксон, а як препарат порівняння  - метамізол натрію. Поведінкові реакції досліджували в тесті "відкрите поле". Гостру токсичність визначали in vivo за методом В.Б. Прозоровського. Результати обробляли за допомоги програми STATISTICA 10.0.

Результати й обговорення. Найменша з випробуваних доз сполуки IFT_247 5 мг/кг спричинила слабкий знеболювальний ефект на рівні тенденції (приріст 34,9%). Збільшення дози до 15 мг/кг спричинило більший ефект (приріст 68,1%, p<0,01). Ефект дози 25 мг був найбільшим (приріст 149,6%, p<0,001), а підвищення дози до 35 мг/кг не посилювало його (приріст 135,9%, p<0,001). Отже, аналгетична дія сполуки IFT_247 залежить від дози, а максимальною ефективною можна вважати дозу 25 мг/кг і саме її взято для наступних експериментів. Аналіз даних вивчення опіоїдергічного механізму сполуки IFT_247 демонструє, що блокатор опіоїдних рецепторів налоксон не вплинув на її знеболювальний ефект. Ця сполука per se збільшила ЛП облизування задньої лапи в середньому на 54%. На тлі дії налоксону ЛП ноцицептивної реакції зріс на 72,8%, відмінності з показником групи досліджуваної сполуки per se відрізняються на рівні тенденції. Для порівняння аналогічний експеримент виконано з класичним анальгетиком-антипіретиком метамізолом натрію. Середній приріст ЛП ноцицептивної реакції за його використання per se становив 306,3%, а за попередньої блокади опіоїдних рецепторів налоксоном - 204,4%, тобто зменшувався в середньому на третину, а медіана фінального латентного часу зменшилася в 2 рази при майже однаковому вихідному значенні. Отже, опіоїдергічний механізм, очевидно, не бере участі в аналгетичній дії сполуки IFT_247, проте тонкий нейрохімічний механізм аналгетичного ефекту сполуки IFT_247 потребує поглибленого з'ясування. У тесті відкритого поля не виявлено суттєвого впливу сполуки IFT_247 на поведінку мишей. Єдиною значущою відмінністю було збільшення кількості болюсів (p<0,05), проте решта показників емоційних реакцій та їх вегетативного супроводу (грумінг, уринації) не відрізнялися від контрольних значень. Таким чином, досліджувана сполука не спричиняє ані стимулюючого, ані пригнічуючого впливу на ЦНС. При визначенні гострої токсичності сполуки IFT_247 доза 2000 мг/кг не викликала летального ефекту в жодної миші. Дози 2500 і 3980 мг/кг спричинили загибель 1 тварини, а доза 5010 мг/кг виявилася летальною для всіх мишей. На підставі цих результатів розраховано ЛД50, що дорівнює 2840±340 мг/кг. Отже, за результатами сполука IFT_247 належить до малотоксичних речовин (500 мг/кг < ЛД50 < 5000 мг/кг, IV клас токсичності за класифікацією Нoge та Sterner).

Висновки. Сполука IFT_247 чинить дозозалежний знеболювальний ефект, максимально ефективною є доза 25 мг/кг. У механізмі аналгетичної дії сполуки не бере участі опіоїдергічний вплив. Дана сполука не викликає змін поведінки мишей у тесті відкритого поля та належить до IV класу токсичності - малотоксичні речовини.

Abstract

Derivatives of 5,7-diacyl-3-H(alkyl)-6-aryl-5H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazine.

Aim. To evaluate the dose dependence of the analgesic effect of the compound IFT_247, the participation of the opioidergic component in the mechanism of action of this compound, its influence on behavioral reactions in the open field test, and to determine acute toxicity.

Materials and Methods. The compound IFT_247 was chosen as the object of research. 80 white outbred male mice were used in the study. Research on somatic pain was conducted using the "Hot Plate" test. Naloxone was used as a competitive opioid receptor blocker, and metamizole sodium was used as a comparison drug. Behavioral responses were studied in the open field test. Acute toxicity was determined in vivo according to the method of V.B. Prozorovsky. The results were processed using the STATISTICA 10.0 program.

Results and Discussion. The lowest tested dose of compound IFT_247, 5 mg/kg, produced a weak analgesic effect at the trend level (34.9% increase). Increasing the dose to 15 mg/kg produced a greater effect (68.1% increase, p<0.01). The 25 mg dose effect was the largest (149.6% increase, p<0.001), and increasing the dose to 35 mg/kg did not increase it (135.9% increase, p<0.001). Therefore, the analgesic effect of the compound IFT_247 depends on the dose, and the maximum effective dose can be considered to be 25 mg/kg, it is this dose that was taken for the following experiments. Analysis of the data from the study of the opioidergic mechanism of the compound IFT_247 demonstrates that the opioid receptor blocker naloxone did not affect its analgesic effect. This compound per se increased hindpaw licking LP by an average of 54%. Against the background of the effect of naloxone, the LP of the nociceptive reaction increased by 72.8%, the differences with the indicator of the group of the studied compound per se differ at the level of the trend. For comparison, a similar experiment was performed with the classical analgesic-antipyretic sodium metamizole. The average increase in the LP nociceptive response during its use per se was 306.3%, and during the previous blockade of opioid receptors with naloxone - 204.4%, that is, it decreased on average by a third, and the median of the final latent time decreased by 2 times with almost the same initial value. Therefore, the opioidergic mechanism is not involved in the analgesic effect of the IFT_247 compound, however, the subtle neurochemical mechanism of the analgesic effect of the IFT_247 compound needs further clarification. In the open field test, no significant effect of the compound IFT_247 on the behavior of mice was found. The only significant difference was an increase in the number of boluses (p<0.05), however, the remaining indicators of emotional reactions and their vegetative accompaniment (grooming, urination) did not differ from the control values. Thus, the studied compound does not cause either a stimulating or depressing effect on the CNS. When determining the acute toxicity of the compound IFT_247, a dose of 2000 mg/kg did not cause a lethal effect in any mouse. Doses of 2500 and 3980 mg/kg caused the death of 1 animal, and a dose of 5010 mg/kg was lethal in all mice. Based on these results, the LD50 was calculated, which is 2840±340 mg/kg. Therefore, according to the results, the compound IFT_247 belongs to low-toxic substances (500 mg/kg < LD50 < 5000 mg/kg, toxicity class IV according to Noge and Sterner classification).

Conclusions. The IFT_247 compound exerts a dose-dependent analgesic effect, the maximum effective dose being 25 mg/kg. Opioidergic influence is not involved in the mechanism of analgesic action of the compound. This compound does not cause changes in the behavior of mice in the open field test and belongs to the IV toxicity class - low-toxic substances.