Aim: to investigate the factors of bacterial virulence of oral microbiotopes against the background of long-term experimental action of an opioid analgesic.
Materials and Methods:The study was performed on 72 white outbred rats, which were injected “Nalbuphine” with a gradual increase in dose for 12 weeks.
The microbial composition and virulence factors of bacteria in the microbiotopes of the oral cavity were studied.
Results: At the end of the 4th week of opioid exposure, the appearance of hemolytic escherichia was noted. At the end of the 8th week the appearance of
capsular bacteria Klebsiella was registered, as a virulence factor. The production of staphylococcal virulence factors – lecithinase, was noted. At the end of the
12th week of opioid use, the appearance of phycomycete fungi was noted, Gram-negative diplococci, Klebsiella, Hemolytic Escherichia coli and Pseudomonas
aureginosa. These changes indicated the development of dysbiotic changes, as well as the gradual formation of foci of the inflammatory process in the oral cavity.
   Conclusions: In the short-term stages of opioid exposure, changes in biocenoses were manifested in an increase in the contamination of certain types of
microorganisms. In the long-term effects of the opioid, the activation of bacterial elements of the microbiocenosis was revealed, which were characterized by
increased expression of virulence factors. At the later stages of opioid exposure, the predominance of gram-negative microflora and the activation of cytotoxic action against the background of suppressed activity of the body’s protective response were established.
KEY WORDS: experiment, oral cavity, microbiotopes, opioid, rats, microorganisms, virulence factors

УДК 611.314.17-018.25:615.212.7

УДК:611.84:611.16 ̸ .018.7.019

   Рогівка є важливим компонентом діоптричного апарату ока. Її унікальна структура забезпечує ідеальну прозорість та надає їй світлозаломлювальних властивостей. Актуальними проблемами теоретичної та практичної медицини сьогодення є опрацювання методів реконструкції окапри його травматичних ушкодженнях різного генезу. Серед яких, проникаючі травми та пошкодження очного яблука, які вимагають проведення реконструктивної хірургії з метою максимального відновлення уражених структур в тому числі і рогівки. Проте, частим ускладненням післяопераційної репаративної регенерації рогівки є формування у ній сполучнотканинного рубця, що значно знижує її оптичні властивості і якість бачення в цілому. Метою роботи було мікро- та субмікроскопічне дослідження структурної організації рубця рогівки після проникаючої механічної травми ока. Матеріалом для досліджень слугували зразки рогівки з ознаками рубцювання 19-ти пацієнтів після 12-ти місяців від моменту виник-нення проникаючої травми. За допомогою світлової мікроскопії вивчали поперечні зрізи рогівки, проводили електронно-мікроскопічні дослідження та вивчали кількісний аналіз змін товщини рогівки у парарубцевій та рубцевій зонах у динаміці. Результати та підсумок. Проведене морфологічне дослідження стану рогівки ока після проникаючих травм засвідчило вростання і проліферацію епітелію в строму рогівки у місцях розриву передньої пограничної мембрани та її гіпертрофію по краях дефекту. Серед клітинних елементів окрім кератоцитів з’являються не характерні для нормальної рогівки фібробласти, які відповідають за синтез волокнистих елементів та протеогліканів та міофібробласти, які, завдяки своїм контрактильним властивостям, забезпечують максимальне ущільнення рубця. Тому, репарація супроводжується певними проблемами у вигляді зниження прозорості, що пов'язано з дезорганізацією строми рогів-ки, а також виникнення оптичних аберацій, викликаних контракцією фіброзної тканини внаслідок її перебудови в місці сформованого рубця.
Ключові слова: очне яблуко, оболонки ока, патологія, поранення ока, травма ока, рогівка, регенерація, рубець.

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.