ДОСЛІДЖЕННЯ ВПЛИВУ ПОТЕНЦІЙНОГО ЛІКАРСЬКОГО ЗАСОБУ З ПРОТИЗАПАЛЬНОЮ ТА ПРОТИМІКРОБНОЮ АКТИВНІСТЮ НА СТРУКТУРНІ ЗМІНИ СЛИЗОВОЇ ОБОЛОНКИ ПІХВИ НА МОДЕЛІ ТРАВМАТИЧНОГО ВАГІНІТУ

The aim of the work. Exploring structural changes in the mucous membrane of the vagina of the rats after the simulation of traumatic vaginitis and the effect of the combined suppository with anti-inflammatory and antimicrobial activity. Materials and Methods. Animals reproduced the model of traumatic vaginitis, after which the investigated drugs were introduced into the vagina in the form of a suppository. The investigated potential medicinal product contained ibuprofen, clotrimazole and metronidazole in the form of suppositories. Neo-Penotran® (Comparative Preparation) in its composition had miconazole and metronidazole. Both drugs included an identical basis – witepsol. The study material was the samples of the vagina of the rats, which were selected for histological examination. Results and Discussion. In the simulation of traumatic vaginitis in rats, dystrophic changes in epithelial cells and a decrease in the thickness of the vaginal mucosa, vascular hyperemia, leukocyte infiltration, and, to a lesser extent, regeneration were observed. The introduction of the investigated potential medicinal product and the comparator product positively influenced the recovery processes of the vaginal mucus. The structural manifestations of the restorative process were proliferative changes in the epithelium and an increase in the density of fibroblasts in their own plate of the mucous membrane. A statistically significant increase in the thickness of the epithelium is established. Conclusions. A conclusion is made on the prevention of dystrophic vaginal changes in the use of the investigational medicinal product and the comparison product on the model of traumatic vaginitis, the tread effect on the epithelium of the vaginal mucosa and the anti-inflammatory effect of ibuprofen in combination with antimicrobial agents.Мета роботи. Дослідити структурні зміни слизової оболонки піхви щурів після моделювання травматичного вагініту та впливу комбінованих супозиторіїв з протизапальною та протимікробною активністю. Матеріали і методи. Тваринам відтворювали модель травматичного вагініту, після чого у піхву вводили досліджувані лікарські засоби у вигляді супозиторіїв. Досліджуваний потенційний лікарський засіб містив ібупрофен, клотримазол і метронідазол у вигляді супозиторіїв. До складу Нео-Пенотрану® (препарат порівняння) входили міконазол і метронідазол. Обидва лікарські засоби включали ідентичну основу – вітепсол. Матеріалом дослідження були зразки піхви щурів, які було відібрано для гістологічного дослідження. Результати й обговорення. При моделюванні травматичного вагініту в щурів спостерігали дистрофічні зміни епітеліоцитів і зменшення товщини слизової оболонки піхви, гіперемію судин, інфільтрацію лейкоцитів, меншою мірою регенерації. Введення досліджуваного потенційного лікарського засобу та препарату порівняння позитивно вплинуло на відновні процеси слизової оболонки піхви. Структурними проявами відновного процесу були проліферативні зміни в епітелії та збільшення щільності фібробластів у власній пластинці слизової оболонки. Встановлено статистично значуще збільшення товщини епітелію. Висновки. Зроблено висновок про запобігання дистрофічним змінам піхви при застосуванні досліджуваного лікарського засобу та препарату порівняння на моделі травматичного вагініту, протекторну дію щодо епітелію слизової оболонки піхви та протизапальну дію ібупрофену в комплексі з протимікробними засобами

Electrophysiologic research of surgically restored median nerve (experimental study).

In the experiment the possibility of providing effective regeneration of the injured median nerve in conditions of creation “protected” suture with intact ulnar nerve was studied. Experimental animals were divided into 4 groups: 1) complete neurotomy of the median nerve; 2) complete neurotomy of the median nerve with neurorrhaphy; 3) complete neurotomy of the median nerve and anastomosis creation between the median and the ulnar nerves in the distal site; 4) complete neurotomy of the median nerve and its neurorrhaphy with the anastomosis between the median and the ulnar nerves in the distal site. The histological study was carried out to identify the level of the nerve regeneration, state of the nerve distal segment and electrical conductivity of the surgically restored nerve on day 30 after the trauma. Morphometric and electrophysiological examinations showed that anastomosis creation allows to prevent atrophy and elimination of distal segment of median nerve and activate regenerative process in the injured nerve. The electrical conductivity of the nerve improved. An increased M-response of the forearm muscles was observed in groups with the anastomosis between the median and the ulnar nerves (the level of M-response recovery in the group 2 – 27,1%, group 3 – 18, 9%, group 4 – 84,6%). According to the study results we have made a conclusion that reinnervation of the muscles at an early stage of the median and the ulnar nerves regeneration was realized with the participation of high-threshold myelin nerve fibers

Granulocyte colony-stimulating factor induces the migration of non-resident cells to intracerebral hemorrhage

The aim of the study is to determine the effect of granulocyte colony-stimulating factor (rHuG-CSF) on the migration of non-resident cells into the region of intracerebral hemorrhage (ICH), which can potentially be considered as mesenchymal stem cells. Materials and methods. In the experiment, unilateral ICH was simulated in rats by injection of autologous blood into the right hemisphere. Immunohistochemical method was used to study perihematomal area on day 1, 3, 10, 30, and 60 after ICH modeling. The appearance of cells expressing CD44, CD68, and CD146 markers was evaluated on a 3-point scale after penetrating trauma (PT) of the brain, ICH, and ICH with the growth factor injection (ICH/rHuG-CSF). Results. In contrast to PT, ICH intensified the infiltration of CD44+ cells in the perihematomal area of the brain and caused the appearance of CD68+ and CD146+ cells in hemorrhage. The specific density of CD44+ cells was decreased on day 60 after ICH, and the effect of rHuG-CSF consisted in reducing the density of CD44+ cells on days 30 and 60. The appearance of CD68+ and CD146+ cells in the perihematomal area was seen after 10 days and further their detection was rare, while after the rHuG-CSF injection, the infiltration by cells with a similar immunophenotype was detected on day 3 ICH with a tendency to accumulate. Conclusions. Infiltration by cells expressing CD44, CD68, and CD146 into the perihematomal area of the rat brain was heterogeneous as to the time after brain injury. The appearance of cells with specified immunophenotype could be associated with hematoma elimination, angiogenesis processes, and other mechanisms of the perihematomal brain region remodeling, in which mesenchymal stem cells were involved. rHuG-CSF modulated the migration of CD68+ and CD146+ cells, which consisted in their earlier and more intense migration to the damaged area of the brain after ICH

FEATURES OF USING ORTHOPEDIC IMPLANTS ON AN EXPERIMENTAL MODEL OF SENSITIZATION TO NICKEL (NI)

Introduction. The theme of metal hypersensitivity (MHS) reactions is among the most controversial and complex issues in orthopedic and trauma practice. MHS diagnoses are diagnostically challenging because they are exclusionary diagnoses. It is currently uncertain which biomarkers can reliably predict a potential pathological response to implants. The aim of this research is to investigate hypersensitivity reactions to orthopedic implants containing nickel (Ni). Materials and methods. This research was conducted on female Wistar rats in accordance with the standards of bioethical principles. To obtain conclusive results, the animals were divided into two experimental groups: with prior sensitization to Freund's adjuvant containing Ni and without it. Nickel plates with a total surface area of 24 mm2 were implanted in the rats under general anesthesia. Five months after the intervention, the animals were removed from the experiment, and histological examination of the obtained samples was conducted. Extracted implants were examined using electron microscopy to assess the implant surface. The local elemental composition of the implants was analyzed using an energy-dispersive spectrometer. Results. Under the experimental conditions, it was demonstrated that after 5 months following the operation, a dense connective tissue capsule with an inflammatory infiltrate in the capsule lumen had formed around the implants in the rats. This suggests a possible manifestation of hypersensitivity reactions to implants containing Ni. Electron microscopy of the surface of the extracted implants revealed corrosion phenomena in all the samples. The degree of corrosion was more pronounced in the group of animals with prior sensitization to Ni, and distant particles of Ni were detected, which can be characterized as the beginning of implant degradation. Conclusions. A connective tissue capsule forms around the implants, and it was found to be 34.8% denser in animals sensitized to Ni prior to implantation, which may indicate tissue reactions with signs of hypersensitivity. Further research will provide a deeper understanding of the fundamental inflammatory and immunological reactions to metals present in implants. This, in turn, will facilitate the identification of clinically useful applications necessary for the development of diagnostic or prognostic tests for patients with metal implants

Toxicological and morphological aspects of nano-TiO2 and nano-TiO2-Ag acute action on the liver of mice

Aim. To study the toxic effect of TiO2 and TiO2-Ag nanopowders on the morphology and elemental composition of the laboratory mice liver. Materials and methods. The study used a model of acute intoxication on laboratory animals. Mice were injected intraperitoneally with TiO2 and TiO2-Ag nanopowders at 4000 mg/kg, 7000 mg/kg, or 10000 mg/kg doses. During two weeks, the animals were observed, lethality was assessed, the accumulation of nanopowder in the organ and the morphology of liver tissues were investigated. The content of titanium and silver in liver samples was determined by optical emission spectroscopy with inductively coupled plasma. Liver tissue micropreparations were examined using an Olympus BX51 light microscope. Also, the micropreparations of the liver were examined by scanning electron microscopy (SEM) using the Tescan Mira 3 device, and the elemental composition was determined using an energy dispersive spectrometer Oxford instrument, X-max 80 mm2. Results. The dependence of the mice lethality on the nanopowders dose was revealed; mortality was higher when exposed to nano-TiO2-Ag compared to nano-TiO2. Average lethal doses were calculated using probit analysis. For nano-TiO2, the LD50 is 4783.30 mg/kg; for nano-TiO2-Ag – 724.44 mg/kg. The accumulation of titanium, titanium, and silver in the liver after exposure to nano-TiO2 and nano-TiO2-Ag was established. In general, there was a tendency to increase the content of titanium in the skin tissue with an increase in the administered dose of nanopowders. Morphological changes in the liver were studied by histological methods. The most characteristic morphological signs of the toxic effect of nano-TiO2 on tissue were dystrophic changes at the level of 67.7 % (cytoplasmic vacuolization in hepatocytes), and when exposed to nano-TiO2-Ag – initial necrotic changes at the level of 70 % (hepatocytes with nuclear pyknosis). It is worth noting that the toxic effect of nano-TiO2 and nano-TiO2-Ag is much less often manifested by focal necrosis and inflammatory reactions (focal infiltration), in some cases, there were adaptive changes that provoked an increase in the number of binuclear hepatocytes. In case of detection agglomerates of a foreign object (crystalline inclusions) were obtained, which were examined spectrally and showed a high content of titanium (Ti). SEM morphometry showed that the size of nanoparticles and their agglomerates ranged from 80 nm to 20 μm. Conclusions. The lethality of mice was higher when the composition of nano-TiO2-Ag was introduced compared to nano-TiO2. Based on the calculated average lethal doses, both nanopowders were assigned to the 3rd class (moderately dangerous) of the danger of chemical substances according to the classification of GOST 12.1.007-76. It was established that with an increase in the injected dose in the tissue of the products of laboratory mice, the accumulation of titanium (under the action of nano-TiO2) and titanium and silver (under the action of nano-TiO2-Ag) increases. Characteristic microscopic signs of the toxic effect of TiO2 and TiO2-Ag nanopowders after intraperitoneal injection in laboratory bags are dystrophic changes in hepatocytes, necrosis of parenchymal disease, while inflammatory reactions occur less often. SEM and the method of elemental mapping of titanium confirmed the presence of TiO2 nanoparticles and their agglomerates in skin tissue when TiO2 nanopowder was administered

Assessing the efficacy of various treatment regimens for patients with endocrine ophthalmopathy associated with Graves’ disease

Purpose: To assess the efficacy of various treatment regimens for patients with EO associated with Graves’ disease based on the retrospective analysis of clinical data, thyroid-stimulating hormone (TSH) receptor autoantibodies (TSHR-Ab) titers and orbital ultrasound imaging findings. Material and Methods: We retrospectively reviewed the medical records (including clinical and laboratory data and findings of ultrasound imaging of retrobulbar adipose tissue) of 155 patients with EO associated with Graves’ disease and either euthyroidism (in the presence of antithyroid therapy) or postoperative compensated hypothyroidism that underwent treatment at Komisarenko Institute for Endocrinology and Metabolism between 2009 and 2019. The duration of EO ranged from 8 months to 36 months. Patients with EO associated with Graves’ disease were medically treated in the presence of stable euthyroidism. Patients were divided into 4 groups based on the glucocorticoid treatment scheme. Group 1 of 15 patients received prednisolone tablets per os; group 2 of 68 patients, intravenous methylprednisolone (MP) pulse therapy only; group 3 of 32 patients, intravenous MP pulse therapy plus vitamin D3; and group 4 of 40 patients, intravenous MP pulse therapy 8 to 12 months after thyroidectomy. Results: As soon as 3 months after treatment initiation, there was an improvement in condition of patients in all groups as assessed by clinical examination, followed by further improvement by 6 months and 12 months. The best results were obtained in patients of group 4, with a statistically significant improvement in clinical condition (p < 0.05). Retrobulbar adipose tissue thickness as assessed by orbital ultrasound at baseline and at 6 months and 12 months was statistically significantly greater in patients of all the four groups than controls (p < 0.05). At 6 months, serum TSHR-Ab levels in groups 1, 2 and 3 significantly decreased compared to baseline, with no significant difference between these groups, whereas serum TSHR-Ab level in group 4 was significantly higher than in other groups both at baseline and at 6 months. At 12 months, serum TSHR-Ab level in group 4 was significantly lower (р < 0.05) than in other groups (2.41 ± 0.81 mU/L versus 5.97 ± 1.71 mU/L for group 1, 5.49 ± 1.27 mU/L for group 2, and 6.17 ± 1.18 mU/L for group 3). Conclusion: Patients with EO associated with Graves’ disease in group 4 (intravenous MP pulse therapy after thyroidectomy) showed a significantly better (р < 0.05) treatment outcome than patients in other groups. Ultrasound imaging of retrobulbar adipose tissue thickness is inadequately informative for assessing treatment efficacy

Research of fluoride ions with the electrode “ECOM-F”

The influence of pH and series of interfering ions on the fluoride-selective electrode “ECОМ-F” function have been investigated. The optimal composition of background solution including the citric buffer, strong indifferent electrolyte and masking agent for interfering ions has been selected

Correlation analysis of electroneuromyographic, functional-anatomical and morphometric indicators of regeneration of the injured sciatic nerve

Objective. To study the electrophysiological, functional-anatomical and morphometric indicators of the sciatic nerve regeneration after complete transection and connection of the nerve stumps with epineural sutures and adhesives. Materials and methods. The experiments were carried out on white outbred male rats. The efficiency of sciatic nerve regeneration was investigated with the standard 4-6 epineural sutures and the use of polyethylene glycol hydrogel Duraseal or Tisseel fibrin glue with 2 fixation sutures. On the 14th, 30th and 60th days after the complete transection of the sciatic nerve and subsequent connection of the nerve stumps with epineural sutures, hydrogel or fibrin glue, limb function was assessed using SFI test and ENMG. The distal segment of the nerve was sampled for electron microscopic and morphometric studies. The density of the regenerated myelinated nerve fibers was studied and a correlation analysis was performed with the results of SFI test and ENMG. Results. The use of adhesives provides a similar result of connecting the transected sciatic nerve, as in standard neurorrhaphy, and regeneration of myelinated nerve fibers in the distal nerve. The regeneration density of myelinated nerve fibers significantly increased on the 30 th and 60th days in the groups in which Duraseal hydrogel and Tisseel fibrin glue were used, without a statistically significant difference in ENMG parameters (M-response amplitude, nerve conduction velocity, latency period) and the result of SFI test. The amplitude of M-response on the 30th day was statistically significantly lower after the connection of nerve stumps with Tisseel fibrin glue in comparison with the Duraseal hydrogel, whereas on the 60th day there was no difference according to the results of electrophysiological studies. Conclusions. The efficiency of sciatic nerve regeneration after the combined connection exceeds the standard technique, and the results of pathophysiological assessments are more often correlated with morphometry data on the 30th day

Correction: Model of excision of the lateral half of the spinal cord at the lower thoracic level for the needs of reconstructive neurosurgery and neurotransplantation

Corrections to the article: https://doi.org/10.25305/unj.234154 In the article by V.V. Medvedev et al., published in UNJ № 3 in 2021, the source number 92 from the reference list does not support the statement given in the appropriate place in the text. Instead, we offer the reader two other works that mention the presence of posterior median spinal artery in the adult rat - D. Mazensky et al. (2017) and O.U. Scremin (G. Paxinos, ed.; 2015, p. 1003, 1005). In most works on this topic (Z. Zhang et al., 2001; Y. Cao et al., 2015; P. Li et al., 2020) the dorsal median vein is considered as the median vessel of the posterior surface of the rat spinal cord, and as in humans, describe 2 parallel dorsal spinal arteries. At the same time, D. Mazensky et al. (2017), sharing the opinion of O.U. Scremin (2015), mention 3 dorsal spinal arteries of the rat, in particular the median one. Taking into account that, from our experience, damage to the median vessel of the posterior surface of the spinal cord is accompanied by its rapid edema and irrepversible deep deficit in the motor function of both hind limbs of the animal, we consider it necessary to draw the reader's attention to this feature of the anatomy of the spinal arteries of an adult rat. Medvediev VV, Abdallah IM, Draguntsova NG, Savosko SI, Vaslovych  VV, Tsymbaliuk VI, Voitenko NV. [Model of spinal cord lateral hemi-excision at the lower thoracic level for the tasks of reconstructive and experimental neurosurgery]. Ukr Neurosurg J [Internet]. 2021 Sep 27 [cited 2021 Oct 11];27(3):33-5. Available from: http://theunj.org/article/view/234154 Cao Y, Wu T, Yuan Z, Li D, Ni S, Hu J, Lu H. Three-dimensional imaging of microvasculature in the rat spinal cord following injury. Sci Rep. 2015 Jul 29;5:12643. doi: 10.1038/srep12643. PMID: 26220842; PMCID: PMC4518284. Li P, Xu Y, Cao Y, Wu T. 3D Digital Anatomic Angioarchitecture of the Rat Spinal Cord: A Synchrotron Radiation Micro-CT Study. Front Neuroanat. 2020 Jul 22;14:41. doi: 10.3389/fnana.2020.00041. PMID: 32792915; PMCID: PMC7387706. Mazensky D, Flesarova S, Sulla I. Arterial Blood Supply to the Spinal Cord in Animal Models of Spinal Cord Injury. A Review. Anat Rec (Hoboken). 2017 Dec;300(12):2091-2106. doi: 10.1002/ar.23694. Epub 2017 Oct 13. PMID: 28972696. Paxinos G, editor. The rat nervous system. 4th ed., London: Elsevier; 2015. Scremin OU. Capter 31, Cerebral Vascular System; p. 985‒1011. Zhang Z, Nonaka H, Nagayama T, Hatori T, Ihara F, Zhang L, Akima M. Circulatory disturbance of rat spinal cord induced by occluding ligation of the dorsal spinal vein. Acta Neuropathol. 2001 Oct;102(4):335-8. doi: 10.1007/s004010100377. PMID: 11603808