The article presents data on structural and functional changes of the mucous membrane of the uterine tube in the dynamics of two-, four-and six-week exposure to nalbuphine. The material of the study were sexually mature rats-females of the line "Wistar" in the amount of 26 animals weighing 180-220 g, aged 3.5-4 months. Animals were injected with nalbuphine intramuscularly, daily, once a day, at the one-time interval. Histological preparations were prepared according to the conventional method. The animals were kept in a vivarium, the work was carried out following the "Rules of work using experimental animals". Before sampling, the animals were primed with an intraperitoneal injection of thiopental (at a rate of 25 mg/kg), then an anterior abdominal wall was opened, followed by removal of the fallopian tube. During the experimental research, changes in the structure of the mucous membrane of the fallopian tube were established. The first signs were found within 2 weeks of the experimental effect of nalbuphine: swelling of the mucous membrane of the fallopian tube, slight smoothing of the folds and local desquamation of the epithelium, moderate infiltration of lymphocytes of the mucous membrane. Vascular microcirculatory vessels of the mucous membrane are slightly expanded. After 4 weeks of the experiment, degenerative and inflammatory changes in the uterine tube wall and manifested by swelling and polymorphocellular infiltration of the membranes of the wall of the test organ wall, an increase in the number of altered epitheliocytes, vessels are hyperemic, overflowing with aggregated erythrocytes, sometimes containing neutrophilic granulocytes and lymphocytes. After 6 weeks of administration of nalbuphine, destructive changes in the cells of the mucous membrane of the fallopian tube and the links of its hemomicrocirculatory bed accrue, manifested by desquamation of the epithelium of the mucous membrane, infiltration of the mucous membrane by lymphocytes, there is an expansion of the lumen of the vessels of the microcirculatory bed and filling the lumen of the blood plasma, there are lashes of different heights, the characteristic grouping of them into conglomerates.

The use of opioids is an effective method of treatment for severe and acute pain; however, when they used inappropriately, in addition to their powerful pain-relieving properties, opioids cause significant side effects. The initial changes in the human body caused by the use of narcotic substances (opiates) are detected in the oral cavity, in particular, in the salivary glands. The earliest manifestations of pathological changes in the oral cavity are caries, stomatitis, gingivitis, periodontitis and xerostomia. Based on the results of our research and the study of the effect of opioids on other organs, we can conclude that long-term use of opioids has a significant negative effect on the structure of the submandibular gland and homeostasis of the oral cavity as a whole. The presence of a number of unsolved questions regarding the problems of structural reconstruction of the salivary glands during the use of narcotic agents, as well as the possibility of selecting the most effective methods of treatment and prevention of salivary gland diseases determined the choice of this research topic. Materials and methods. The research was performed on 15 mature, white, male rats with body weight 200–220 g, aged 4.5–6 months, which were kept under standard conditions at the vivarium of the Danylo Halytsky Lviv National Medical University. Animals were divided into two groups: experimental and control. In the experimental group, animals (10 rats) were daily administered an opioid analgesic (nalbuphine) intramuscularly according to the following schedule: 1st week – 8 mg/kg, 2nd week – 15 mg/kg, 3rd week – 20 mg/kg, 4th week – 25 mg/kg, V week – 30 mg/kg. Controls were 5 rats that were injected with 0.9% sodium chloride solution in a volume of 1 ml for 5 weeks. We used the histological method to conduct the research. Results. Damage to the organs of the oral cavity and the submandibular gland, in particular, is an element of comorbid pathology caused by long-term use of opioids. During the 5-week administration of the opioid, we observed irreversible destructive changes in the structural organization of the submandibular gland, which was characterized by the dilation of the vessels of the microcirculation, dystrophic and necrotic changes of the final serous and mucous secretory acini, necrosis of serocytes. Such pathological processes in the structural organization of the submandibular gland can cause an imbalance in the quantitative and qualitative composition of saliva and, as a result, a violation of the homeostasis of the oral cavity and the upper parts of the gastrointestinal tract. Conclusions. The results of the research demonstrate the negative impact of long-term opioid exposure on the structural organization of the submandibular gland and are similar to changes in other organs and body systems during long-term opioid exposure. The damage to microcirculation vessels is the starting and primary mechanisms in this process with the subsequent increase of irreversible destructive changes of the submandibular gland. The data of the scientific work have a wide practical and theoretical significance for morphologists, pathomorphologists and dentists in the aspect of developing new methods of diagnosis, prevention and treatment of salivary gland pathology in patients with opiomania and make it possible to establish safe terms of use of «nalbuphine».

Introduction. In the modern world, the problem of drug use, especially among the youth, is considered to be of utmost importance. Female body’s susceptibility to the development of drug addiction is considerably higher than that of the male body. The study of blood supply of the uterine tube is relevant since the morphological rebuilding of the mucous membrane of the uterine tube, considering its functions, plays an important role in the pathogenesis of several diseases of the female reproductive system. Under the effect of pathological factors, including opioids, vessels became the main target, and their structural changes are the basis for the development of the pathological process and determine the peculiarities of clinical symptoms. Methods. The study was carried out on 34 sexually mature white female rats (4,5-6,0 months) with the bodyweight of 180-220 g. Angioarchitectonics of the uterine tube of female white rats was studied in double-blinded, placebo-controlled studies with distribution into a control group (intact rats that were accepted as a relative norm, n=10), a placebo-controlled group (n=9) that received 0.9% saline for the duration of the experiment, and 3 experimental groups (n=5 each) that were subjected to long-term opioid effect. Results. After 2 weeks of Nalbuphine administration for female white laboratory rat, the minor expansion of arterioles and capillaries was observed, their diameter increased. Arteriolovenular coefficient augmented. After 4 weeks of Nalbuphine administration, arterioles were convoluted, loss of clear outlines, expansion of lumen, irregularity of vessels caliber, microvessels with microaneurysms, areas with hemorrhage and obliteration of capillaries were detected. After six-week administration of nalbuphine, the hemomicrocirculatory blood flow of the uterine tube wall was at the stage of decompensation, the capillary component was almost destroyed, arterioles were abruptly twisted and distorted, their lumen was uneven, venules were expanded and distorted, additional arteriolovenular anastomoses were opened, indices of trophic activity of the tissue increased considerably. Conclusions. The vasotropic effect after six-week administration of nalbuphine demonstrated severe damage to the uterine tube hemomicrocirculatory blood flow.

The aim is to investigate changes in the microbiota of dental biofilm at the end of the eighth, tenth and twelfth weeks of experimental opioid exposure. Materials and methods: The study was performed on 36 white outbred adult male rats, which were injected with the opioid analgesic nalbuphine in increasing doses (0,212 – 0,3 mg / kg) during 8, 10 and 12 weeks. Qualitative and quantitative composition of microbiota of dental biofilm was studied using statistical analysis. Results: After eight weeks of opioid exposure, changes in microbiocenosis of dental biofilm of rats were caused by a significant increase in saprophytic and opportunistic microbiota and an appearance of pathogenic species of indicator microbiota with potential periodontopathogenic action. At the end of the tenth week, a significant increase in the quantitative indicators of certain species of opportunistic microbiota and increase in the quantitative composition of pathogenic bacteria were determined. After twelve week of opioid exposure, a significant increase in the quantitative indicators of pathogenic microbiota of dental biofilm was detected. Conclusions: Changes in the qualitative and quantitative composition of the microbiocenosis of the dental biofilm at the end of 8, 10 and 12 weeks of opioid exposure were established, they were manifested by a significant increase in the quantitative indicators of certain species of opportunistic microorganisms and a significant increase in pathogenic microbiota in the dynamics, which led to the progression of dysbiotic changes and purulent-inflammatory process in the oral cavity of rats.

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