Reparative Regeneration Research Articles

ОЦЕНКА КЛИНИКО-БИОХИМИЧЕСКОГО АНАЛИЗА КРОВИ СОБАК С УЧЕТОМ ПРИМЕНЕНИЯ ОСТЕОБИОКОМПОЗИТА ДЛЯ УСКОРЕНИЯ КОНСОЛИДАЦИИ

To date, it is quite important to prevent antibacterial contamination, osteoconductivity and osteoinductivity of the processes of reparative regeneration of bone tissue with the help of coatings for implants, as well as a variety of pharmacological drugs administered systemically or pointwise into the fracture zone. This is necessary to prevent degenerative-dystrophic changes in the osteoarticular system (false joint, arthrosis, resorption, sequestration, slow consolidation, non-fusion, osteoporosis, reduced vascularization), acute and chronic infectious lesions, joint blockage, deformity of tubular bones and disability. This article reflects the studies of clinical and biochemical blood analysis of three groups of animals (dogs) using the developed biocomposite injected into the intramedullary canal with a simulated transverse fracture of the middle third of the radius diaphysis. The components of the composite are used as: a matrix that compensates for parts of the destroyed bone, accelerates the processes of renewal of structural parts of cells, tissues at various stages of organization, while it has a stimulating effect on leuko- and erythropoiesis, as well as the process of phagocytosis, bone formation, prompting osteoprogenitor cells to proliferate and differentiate into osteoblasts. Also, due to the presence of a semi-synthetic broad-spectrum antibiotic (penicillin series), it has a bactericidal effect as a result of inhibition of bacterial cell wall synthesis. It is also worth noting that the developed composite is safely absorbed and biointegrated without reaction to a foreign body. Based on the conducted studies, a group of authors, taking into account the clinical and biochemical analysis, confirmed the absence of inflammatory, allergic, aplastic, hepatotoxic and nephrotoxic reactions from the macro- and micro-organism of animals.

MORPHOLOGICAL FEATURES OF TUBULAR BONES REPARATIVE REGENERATION UNDER THE INFLUENCE OF ANTITUMOR CHEMOTHERAPEUTICS

The aim: Determination of morphological features of reparative regeneration of diaphysis defect of long tubular bones under the influence of antitumor chemotherapeutics in a model experiment. Materials and methods: 96 white nonlinear rats after application of the perforated defect of the femur were administered the appropriate antitumor drug (doxorubicin, 5-fluorouracil, methotrexate) three times with an interval of 21 days. Morphological features of bone tissue formation and remodeling in the regenerate area were studied using histological and morphometric methods. Results: The inhibitory effect of antitumor chemotherapeutics on the formation of regenerate, expressed by slowing down the process of bone tissue differentiation was found. This is confirmed by a decrease in the area of reticulofibrous and lamellar bone tissue, chaotic arrangement and narrowing of bone trabeculae with uneven color, slow formation of bonding lines between the maternal bone and the regenerate. Conclusions: The revealed morphological features of reparative regeneration of the diaphysis defect of long tubular bones under the influence of antitumor chemotherapeutics doxorubicin, 5-fluorouracil and methotrexate in a model experiment indicate a slowing of reparative regeneration processes at all stages of recovery after injury.

Orthopedic rehabilitation of patients in the department of Modern Prosthetics Technologies of the Central Research Institute of Dentistry and Maxillofacial Surgery

The main guidelines for innovative prosthetic technologies and effective methods for replacing defects in hard tissues of teeth and dentitions in patients with pathological abrasion of teeth, secondary deformations of dentitions and generalized periodontitis are implemented in the department of modern prosthetics technologies through the introduction of digital technologies (3D modeling, scanning, printing), development of new methods and techniques of treatment, study of the features of reparative regeneration in the field of dentition defects and changes in the prosthetic bed, analysis of morphological changes in traumatic occlusion, integration with other clinical departments of the institute.

Osteogenesis Hormonal Regulation: Review

Background. The endocrine system occupies a leading place not only in the regulation of growth and development mechanisms, but also in compensation reactions when the body is exposed to extreme factors. Coordinated hormonal regulation contributes to the correct response of the macroorganism adaptive processes, aimed at restoring and maintaining homeostasis. A cascade of endocrine changes accompanies the processes of both physiological and reparative regeneration of bone tissue at all its stages. The aim of the study was to analyze the currently known mechanisms of hormonal regulation of physiological and reparative bone tissue regeneration. Materials and Methods. The search and analysis of scientific literary sources was carried out in the electronic databases PubMed and eLIBRARY. Search depth 10 years. Results. The review considers both fundamental aspects and new data on the main histogenetic mechanisms of osteogenesis hormonal regulation. The ways and points of interaction of the endocrine and skeletal systems are highlighted, the main functions of hormones in the participation of bone remodeling in different age periods are determined. Conclusion. In violations of physiological regulation, hormonal imbalance is assigned a key role, while under conditions of reparative osteogenesis, the role of qualitative and dynamic changes in the endocrine system has been studied insufficiently. Hormonal regulation of reparative regeneration to date has no clear assessment criteria and requires further research.

СРАВНИТЕЛЬНАЯ МОРФОЛОГИЧЕСКАЯ ХАРАКТЕРИСТИКА РЕАКЦИИ ТКАНЕЙ ЭКСПЕРИМЕНТАЛЬНЫХ ЖИВОТНЫХ НА ИМПЛАНТАЦИЮ МОДИФИЦИРОВАННЫХ ПОЛИПРОПИЛЕНОВЫХ СЕТЧАТЫХ ЭНДОПРОТЕЗОВ

Objective. To study cellular and tissue reactions in experimental animals in response to the implantation of a polypropylene mesh endoprosthesis modified with a polycaprolactone solution by the different methods. Methods. The object of the study was modified with polypropylene mesh endoprostheses implanted in experimental animals. The animals were divided into three groups: the control group - with polypropylene mesh endoprosthesis without its modification; the first experimental group - with polycaprolactone modification by its uniform distribution on the endoprosthesis surface; the second experimental group - with the samples of polypropylene mesh endoprosthesis modified by method of electrospinning. The morphological assessment of reactions to the implantation of the materials was carried out by means of the calculation of the cellular elements of inflammatory and connective tissue origin along the periphery of the implants Results.A statistically significant increase in the number of fibroblasts was revealed on the 3<sup>rd</sup> day of observation in the animals of the second experimental group in comparison with the control one (р=0,047). The analogous trend was noted on the 7<sup>th</sup> day of the study in comparison with the control animals (р=0,002), as well as with the animals from the first experimental group (р<0,001). On the 7<sup>th</sup> day of the experiment the enhancement of the fibroplastic properties of the samples modified with polycaprolactone by electrospinning was characterized by a less pronounced inflammatory reaction of the peripheral tissues and it indicates a higher rate of granulation tissue maturation. Conclusion. Tissue and cellular reactions around the specimens modified with with polycaprolactone solution by the electrospinning method were found to be characterized by a less pronounced inflammatory reaction of the peripheral tissues and more expressed fibroplastic reaction in comparison with the control specimens. The endoprostheses obtained in this way can be used to stimulate the migration of fibroblasts and enhance local collagen synthesis, accelerate the processes of reparative regeneration in patients with undifferentiated connective tissue dysplasia. Thus it makes possible to recommend introducing this method of PSE modification in clinical practice. What this paper adds For the first time, morphological features of subcutaneous tissue around samples of polypropylene mesh endoprostheses modified with polycaprolactone solution by the different methods of its application have been studied. The changes in tissues around the samples of polypropylene mesh endoprostheses modified with a polycaprolactone solution by electrospinning are found to be characterized by a low peripheral inflammatory response of tissues with an increase of fibroplastic changes in comparison with control ones.

Reparative regeneration of histogenetically different bones

The bone plates that forming the turtle shell differ in histogenesis. Thus, the costal and neural plates of the carapace (dorsal shield) have mesenchymal origin and develop by indirect perichondral osteogenesis from vertebrae and ribs. The bone plates of the plastron - abdominal shield, are known to be formed from neuroectodermal cells of the neural crest and develop by intramembrane osteogenesis in the dermis of the skin. The aim of the study was to compare the reparative regeneration of histogenetically different bone tissue of the carapace and plastron of freshwater red-eared turtles Trachemys scripta. The experiment was performed on freshwater red-eared turtles Trachemys scripta aged 3 months. 2 defects of carapace and plastron bone plates with a diameter of 5 mm and a depth of up to "soft tissues” were formed with further histological examination. It was found that the regeneration of the bone plates of the plastron is characterized by the formation of bone tissue in a larger volume and at an earlier date. After 30 days a layer of continuous newly formed bone tissue is formed. By 90 days the proportion of bone tissue in the carapace regenerate was 40,5% of the defect area, while in the plastron the regenerate occupied 47,4%. Thus, intramembranous formed bone tissue of neuroectodermal histogenesis has a more pronounced regenerative potential compared to perichondral formed bone of mesenchymal origin.

LIGHT- AND ELECTRON-MICROSCOPIC CHARACTERISTICS OF CHANGES IN THETHYROID GLAND DURING CHRONIC HYPOXIA

The investigation aims were to study the ultrastructural changes in the cellular and extracellular matrices of the thyroid gland in the norm and chronic hypoxia. Materials and methods: 40 male white rats were divided into a test and control group. Animals of the control (I) group (n=20) were not subjected to intervention, in the test group (n=20) a model of chronic hypoxia was created - the animals were kept in a special ventilation barochamber daily for 2 hours 5 times a week. Anatomical, histological, histochemical, electron microscopic and morphometric methods were used. Morphometric parameters were calculated by use of program Statistica 10 (StatSoft.Inc.) (statistical processing was performed using W — Wilcoxon test (paired samples) with the control group). Results: Pathomorphological picture of the thyroid gland of rats subjected to hypobaric hypoxia, on the 15th day of the study was characterized by the acceleration of adaptive processes in gland cells and the development of reparative regeneration. Small structural changes in thyrocytes observed on the 15th day of the experiment show that the gland cells are not completely restored, adaptive processes do not occur completely. The area (12.21±1.43) and the diameter (6.25±0.48) of the nuclei are relatively increased compared to the control group. Analysis of samples from the thyroid gland of animals adapted to chronic hypoxia on the 30th day of the study shows that the gland cells adapted to the new conditions and completely restored their normal structure and size. The morphometric parameters of the thyroid gland were relatively close to the norm (normal cell diameter (5.96±0.38) and the area of the nuclei (12.11±1.43)). Conclusion: The results of the studies showed that under the influence of prolonged hyperbaric hypoxia, the body's resistance to it, especially the thyroid gland, increases, and it adapts to hypoxic conditions, and this is accompanied by the processes of structural reorganization of organs. Thyrocytes of the thyroid gland adapt earlier to chronic hypoxia and respond to this by hyperplasia and hypertrophy and differentiation of thyrocytes.

Концептуальное моделирование репаративной регенерации при оперативном лечении диафизарных переломов

Проведено концептуальное моделирование репаративной регенерации при оперативном лечении диафизарных переломов. Использован системный анализ дооперационных, операционных и послеоперационных факторов влияния на репаративную регенерацию. Перед планированием оперативного вмешательства и выбором метода остеосинтеза и фиксатора должен проводиться системный анализ факторов влияния на репаративную регенерацию, в соответствии с характером перелома. После стабилизации невправленных фрагментов создаются условия для развития псевдоартроза. Достаточно часто процесс осложняется плохой васкуляризацией участков кости либо сдавливанием серкляжами. Анализ факторов влияния на репаративную регенерацию при оперативном лечении переломов имеет большое значение в предвидении их возможных расстройств и осложнений. Концептуальное моделирование репаративной регенерации расширяет понимание биологии процесса сращения отломков.

Состояние репаративной регенерации костной ткани при поражении тазобедренного сустава у больных ревматоидным артритом и анкилозирующим спондилитом

В статье приведен анализ показателей репаративной регенерации 67 образцов спонгиозы костей, образующих тазобедренный сустав, 26 больных ревматоидным артритом и 30 образцов спонгиозы костей, образующих тазобедренный сустав, 18 больных анкилозирующим спондилитом, которым выполнено эндопротезирование тазобедренного сустава. Проведенные нами исследования выявили существенные отличия в эффективности клонирования колониеобразующих единиц фибробластов среди 105 ядросодержащих клеток костного мозга спонгиозы вертлужной впадины, головки и межвертельной области бедренной кости. Полученные данные объективно отображают состояние репаративной регенерации костной ткани в различных участках тазобедренного сустава у этой сложной категории больных.

Оптимизация репаративной регенерации при переломах пяточной кости обогащенной тромбоцитами аутологичной плазмой

Актуальность. Количество неудовлетворительных результатов лечения внутрисуставных переломов пяточной кости достигает 34 %. Поиск оптимальной мини-инвазивной методики лечения, которую можно применить даже в скомпрометированных состояниях, уменьшить травматичность, начать раннюю реабилитацию и оптимизировать процессы репаративной регенерации, является актуальной проблемой. Одним из путей оптимизации процесса репаративной регенерации является применение обогащенной тромбоцитами плазмы. Цель: проанализировать результаты лечения больных с внутрисуставными переломами пяточной кости и оптимизировать репаративную регенерацию костной ткани плазмой с повышенным содержанием тромбоцитов. Материалы и методы. В период 2017–2019 гг. (I полугодие) в отделении травматологии Коммунального некомерческого предприятия «Городская больница № 9» Запорожского городского совета проходили лечение 79 больных с переломами пяточной кости. Двусторонние переломы имели место в 11 случаях (13,9 %). Гендерный состав: мужчины — 71 (89,9 %), женщины — 8 (10,1 %). Механизм травмы: падение с высоты (более 1,5 м) — 47 (59,5 %) человек, бытовые — 32 (40,5 %) человека. Были выполнены следующие оперативные вмешательства: металлоостеосинтез спицами — 62 (74,7 %), винтами — 7 (8,4 %), пластины и аппараты внешней фиксации не применялись. Отказались от оперативного лечения 14 (16,9 %) человек. Результаты. В основной группе пациентов рентгенологическое сращение перелома наступило через 6 недель у 6 больных (85,7 %), у 1 больного (14,3 %) — через 12 недель (случай тяжелого обломочного внутрисуставного перелома). В контрольной группе сращение на 8-й неделе выявлено у 14 пациентов (58,3 %), у 8 (33,3 %) — на 16-й неделе, у 2 пациентов (8,4 %) послеоперационный период осложнился полостью резорбции костной ткани. Выводы. Применение обогащенной тромбоцитами плазмы для регенерации костной ткани имеет значительный клинический потенциал. Предложенная мини-инвазивная методика оперативного лечения в сочетании с введением обогащенной тромбоцитами плазмы позволяет применять ее в осложненных случаях, когда есть противопоказания к оперативному вмешательству.

Photodynamic reparative skin regeneration using application of photosensitizer gel based on chlorin e6

The results of a study of the clinical effectiveness of the correction of involutional changes in the skin by the method of photodynamic therapy (PDT) with the use of a photosensitizer gel (PS), the active substance of which is the trismeglumine salt of chlorin e6, are presented. The data of fluorescence spectroscopy for monitoring the level of PS fluorescence in order to determine the optimal time of its exposure are demonstrated. The study of the optimal exposure time involved 80 patients with different skin phototypes. The study of the effectiveness of PDT involved 42 patients aged 44–68 years with signs of chrono- and photoaging. The PDT procedure was performed by irradiating the entire surface treated with the PS with a power density of 100 mW/cm2, a light dose of 120–140 J/cm2, a laser radiation wavelength of 660 nm, and a light beam area of 400–800 cm2. It was found that exposure to PS for 10–20 min gives the highest fluorescence and does not depend on the skin phototype. The clinical effect of PDT was achieved in 85.7% of patients; there were no negative subjective sensations. Moisture metrics increased on the skin of the face by 53%, reaching the control values in young healthy volunteers, on the skin of the hands - by 64%. Elastometry indicators on the skin of the face and hands increased by 19% and 16%, respectively. Thus, the PDT procedure with PS based on chlorin e6 is an effective method for correcting involutional changes in the skin, leads to a pronounced clinical effect, improves the parameters of skin moisture measurement and elastometry, and passes without undesirable local reactions. Optical coherence tomography showed an increase in collagen ordering.

Морфологічні аспекти репаративної регенерації кісткової тканини в умовах впливу протипухлинної хіміотерапії

The occurrence of fractures in the development of cancer in the body is due to changes in bone metabolism in the form of osteoporosis and metastatic bone damage. Their appearance leads to the postponement or cessation of treatment of cancer, which affects the life expectancy of such patients and the chances of recovery. Antitumor chemotherapy, as one of the main methods of cancer treatment, is prescribed for long-term courses and affects the healing of fractures. However, according to the literature, the effect of antitumor chemotherapeutics on reparative regeneration is poorly understood today. The purpose of the work is to study the morphological features of reparative osteogenesis under the influence of antitumor chemotherapy. Materials and methods. The study was performed on 96 white laboratory male rats 7 months of age weighing 230±10 g. All animals had a perforated defect with a diameter of 2 mm spherical cutter to the bone marrow canal in the middle third of the femoral shaft. Animals were divided into control (n = 24, without chemotherapy) and three experimental groups (I, II, III, n = 72), which after injury and every 21 days of the study were administered intraperitoneal anticancer chemotherapeutics: I (n = 24) – doxorubicin (60 mg / m²), II (n = 24) – 5-fluorouracil (600 mg / m²), III (n = 24) – methotrexate (40 mg / m²). On the 15th, 30th, 45th, 60th days after injury, the animals were removed from the experiment, followed by removal of the injured long tubular bones. Histological preparations stained with hematoxylin-eosin, followed by their morphometry, scanning electron microscopy with the method of X-ray energy dispersion spectroscopy, immunohistochemical examination were performed. Results and discussion. Antitumor chemotherapeutics causes delayed callus formation, which is manifested by an increase in the area of connective and reticulofibrous bone tissue in the regenerate, along with the slow formation of lamellar bone tissue. Chemotherapy leads to disorders of phosphorus-calcium metabolism both in the regenerate and in the maternal bone in the form of reducing the intensity of mineralization of the newly formed bone matrix and slowing down the remodeling activity of the maternal bone. Chemotherapy is accompanied by an increase in the expression of the bone resorption marker cathepsin K and a decrease in the expression of the osteopontin bone marker, which indicates a delay in the formation of regenerate in the area of injury and a decrease in the rate of reparative regeneration. Conclusion. The most pronounced delay in the processes of remodeling of bone regenerate was found with the use of doxorubicin and methotrexate, while 5-fluorouracil showed less inhibitory effect on these processes

Activation of reparative liver regeneration following the combined transplantation of multipotent mesenchymal stromal cells and hepatic stellate cells

Aim. To study the effect of combined transplantation of multipotent mesenchymal stromal and hepatic stellate cells on the reparative liver regeneration.
 Methods. Laboratory mice were given intravenous administration of multipotent mesenchymal stromal and hepatic stellate cells after partial hepatectomy. The mice were divided into four groups: control, experimental 1 (injection of multipotent mesenchymal stromal cells), experimental 2 (co-transplantation of multipotent mesenchymal stromal cells and hepatic stellate cells), the comparison group. Comparison of the experimental groups with the control group and the comparison group was carried out. Each group consisted of 14 animals. The control and experimental groups underwent partial hepatectomy. The experimental mice were injected with the cells into the lateral tail vein 1 hour after the operation. Multipotent mesenchymal stromal cells were administered at a dose of 4 million cells/kg (120 thousand cells/mouse), hepatic stellate cells in the amount of 9 million cells/kg (270 thousand cells/mouse), suspended in 0.2 ml 0.9% NaCl solution. The control group animals were injected with 0.2 ml 0.9% NaCl solution into the lateral tail vein. The comparison group consisted of mice without partial hepatectomy, injected with 0.2 ml 0.9% NaCl solution. To assess reparative regeneration of the liver, morphometric parameters of the liver, blood biochemical parameters on the 3rd and 7th days after partial hepatectomy were studied. The severity of apoptosis was assessed by the immunohistochemical method, the activity of deoxyribonucleic acid (DNA) repair enzymes of the poly (ADP-ribose) polymerases was determined by flow cytometry. The number of micronucleated hepatocytes was also determined. The hepatocyte growth factor (HGF) content was measured by using an enzyme-linked immunosorbent assay in serum. The significance of differences in the compared samples was determined by using the Student's t-test. Statistical data processing was performed by using the SPSS Statistics software version 17.0.
 Results. It was found that the combined transplantation of multipotent mesenchymal stromal and stellate liver cells causes restoration of the activity of alanine aminotransferase (a decrease of 30.3%, p=0.016), aspartate aminotransferase (a decrease of 27.7%, p=0.021), alkaline phosphatase (a decrease of 21.1%, p=0.036), an increase in the protein synthetic function of the liver (increase in albumin level by 36.6%, p=0.009), an increase in hepatocyte growth factor level by 74.3%. These changes were accompanied by the restoration of liver morphometric parameters: there was an increase in the mitotic activity of hepatocytes by 28.7% (p=0.008), the nuclear area of hepatocytes by 26.7% (p=0.006), the number of binucleated hepatocytes by 26.1% (p=0.004), which led to the restoration of liver mass. There was a decrease in the level of apoptosis by 28.8% (p=0.006) and a decrease in the number of micronucleated hepatocytes by 22.7% (p=0.001) compared with the control group, which may be related to an increase in the activity of Poly (ADP-ribose) polymerase repair enzymes detected in the study. The deviations were presented as a difference relative to the indicators of the control group (operated animals that were injected with 0.9% NaCl solution).
 Conclusion. Combined transplantation of multipotent mesenchymal stromal and hepatic stellate cells activates reparative liver regeneration after partial hepatectomy.Keywords: multipotent mesenchymal stromal cells, MSC, hepatic stellate cells, HSC, liver regeneration, partial hepatectomy.

Effect of Platelet-Riched Plasma on Corneal Epithelium Regeneration during Its Chronic Erosion (Experimental Study)

Relevance. In a number of pathological conditions accompanied by defects of the basal membrane, such as chemical or thermal burn, mechanical trauma, Schegren’s syndrome, herpetic keratitis processes of corneal epithelization are slowed down, and sometimes epithelization does not occur at all. Slow epithelization or its complete absence creates conditions for infection, thinning, and sometimes perforation of the cornea. That is why the problem of chronic corneal erosions is very relevant. The most perspective method of treatment is the use of autologous platelet-riched plasma (PRP). Presence of platelet growth factors, adhesive molecules and cytokines in PRP allows to use it for acceleration of regeneration of corneal defects, and the presence of live platelets allows to refer this procedure to autologous cell transplantations.Objective: To evaluate the clinical and morphological features of corneal epithelium regeneration in response to the application of PRP in conditions of experimental chronic corneal erosion (ECCE).Materials and methods. Researches were carried out on 12 rabbits of Chinchilla breed (24 eyes). At first stage the model of ECCE was reproduced for all animals: local ultraviolet (UV) irradiation with the exposure time of 45 min. on the preliminary de-epithelized corneal surface. At the second stage all animals under study were divided into three groups (4 rabbits in each group). I-st main group (MG) was instillated with PRP at a rate of 1 drop / 1 min within 10 minutes (total of 10 drops) once, in the II MG treatment was carried out according to the above method, every day for 5 days. In the control group (CG) PRP treatment was not applied.Results. 45-min. UV irradiation causes persistent ECCE up to 30 days of the experiment and reverts only after surface vessels are ingrowed in the affected area. Single use of PRP has insufficient therapeutic effect. Instillation within 5 days accelerates the cornea reparative regeneration in ECCE conditions. The absence of epithelial defect, newly formed vessels and corneal clouding was registered on the 9th day. Histologically, on the 30th day a normal multilayer non-squamous epithelium was found, while the stroma had an organized structure with no signs of inflammation.Conclusions. Therapeutic effect of PRP in ECCE conditions is based on reforming of the normal «adhesion complex» between epithelium, olfactory membrane and multifactor stimulation of reparative regeneration due to growth factors located in it, adhesive molecules and cytokines, as a result of which the typical corneal epithelium is restored.

Determination of the activity of pyruvate kinase isoforms in normal conditions, in toxic liver damage and during the process of its regeneration

Objective.To evaluate the activity of pyruvate kinase (PK) isoforms in normal conditions, in toxic damage of the liver and during its regeneration.Materials and methods.An experimental study was carried out on 45 Wistar rats. Toxic liver damage was induced by the intraperitoneal administration of carbon tetrachloride. Mechanical damage was simulated by the surgical resection of the liver. The levels of PK isoforms R/L and M in the blood serum and liver tissue of the laboratory animals were measured with an ELISA test.Results.It has been found that the level of PK isoform M signifcantly increases in chronic toxic liver damage, which may indicate the activation of the processes of liver cell proliferation in response to the damaging effect of hepatotoxin (Mann-Whitney U Test: Z = 2.143; p = 0.032). After liver resection, the level of PK R/L, which characterizes the activation of glycolysis, increased and the level of pyruvate kinase M increased signifcantly, which reflected the processes of reparative regeneration in the liver.Conclusion.The serum level of PK isoforms may be used as a laboratory criterion for the activity of reparative regeneration processes, which can be used to evaluate the reparative potential of the liver in case of toxic or mechanical damage, as well as in chronic diffuse diseases.

Biotechnological Techniques to Improve Regenerative Abilities of Liver Tissue in Experimental Cholestasis

The study examined the effect of plant hepatoprotectors obtained in the process of biotechnological techniques and thermal effects on liver tissue to prevent the destruction of cell membranes and stimulate regenerative processes in hepatocytes in experimental models (12 dogs). All animals underwent complex conservative therapy, including a plant hepatoprotector with the code name GTPS-4, containing a purified dry extract from the fruits of milk thistle, dry extract from tansy, St. John’s wort, turmeric, birch leaves and immortelle flowers. Conservative therapy was combined with thermal effects on the liver tissue to enhance reparative regeneration. The combination of herbal preparations and contact coagulation techniques gave the best result, and the optimal combination of herbal preparations in the form of collection was also proposed. The structural and functional state of the liver was assessed according to the results of morphological studies. The performed complex therapy significantly improves the condition of the liver tissues, its regenerative abilities and normalizes homeostasis indicators. The inclusion of plant hepatoprotectors in complex conservative therapy is a promising direction in the development of biotechnology in hepatology.

Dynamics of signs of granulomatous inflammation of the liver after administration of the BCG vaccine in mice of different ages

Purpose of the study. The aim of the study was to study the morphogenesis of granulomatous inflammation in the liver in newborn animals and in remote periods of life.Materials and methods. The experiment was carried out on 70 newborn C57BL / 6 mice, divided into two groups. On the first day after birth, mice of the 1st (experimental) group were injected intraperitoneally with a solution of the BCG vaccine at a dose of 0.02 mg / kg. On the fi rst day of the beginning of the experiment, the mice of the 2nd (control) group were injected intraperitoneally with 0.02 ml of physiological solution. Liver samples were subjected to morphological and morphometric study: the body weight of mice (g), the volumetric density (Vv) of dystrophy and necrosis of hepatocytes, foci of extramedullary hematopoiesis, the number density (Nai) of binuclear hepatocytes, mitotic figures, the diameter of granulomas (μm), and the number density were calculated (Nai) granulomas in test area.Results. The introduction of the BCG vaccine to newborn mice on the 1st day led to a delay in their development and a lack of body weight. With the introduction of the BCG vaccine to newborn mice of the C57B1 / 6 line, a delayed formation of granulomas is noted, starting from the 10th day after the administration of the BCG vaccine, and a subsequent increase by 56 days in both the number and size of granulomas. The foci of extramedullary hematopoiesis in the liver of mice after the administration of the BCG vaccine persist for a longer period (up to 28 days), which is probably due to the participation of cells of the foci of hematopoiesis in the inflammatory process in the liver parenchyma. With the introduction of the BCG vaccine, pronounced destructive changes in hepatocytes in mice at all age periods are noted with reduced rates of reparative liver regeneration. Conclusion. The introduction of BCG vaccine to newborn mice led to the formation of tuberculous granulomas in the liver during the adult period of life with the development of destructive changes in hepatocytes and a reduced reparative ability of the liver.

Reparative histogenesis of bone tissue in femoral fractures in rats using biocomposite material along with immunocorrection

The paper studies the effect of the RVI biocomposite material belonging to the group of osteoplastic biocomposite materials, the RV-2 immunomodulator – a synthetic dipeptide inducing an immunocorrective effect, and combinations of these drugs on the reparative histogenesis of bone tissue in femoral fractures in rats. It was found that the remodeling of the primary bone callus into the secondary one in the fracture of the studied animals was of a diverse nature. This process was the most pronounced in the group where the components were used in complex, i.e. the bone defect was filled with RVI during the surgery, as well as RV-2 was injected intramuscularly to rats at a dose of 10 mcg per 1 kg of live weight for five days, starting immediately after the surgery. Well-formed coarse-fibrous connective tissue callus was recorded in animals of this group. The connective tissue was stained more intensely which indicates a denser arrangement of fibers in the callus. Focal cartilage tissue spanning bone fragments was observed within the callus. At the periphery of the site the cartilaginous callus was subjected to endochondral ossification with replacement by coarse-fibrous trabeculae with elements of lamellar bone tissue having haversian canals in the center. The inter-girdle spaces were filled with elements of the myeloid bone marrow in the forming bone tissue. Markedly proliferated osteoblasts were visible in the cambial layer of the periosteum. The bone tissue ratio increased up to (60.21 ± 2.62)%, which significantly exceeded the same indicator in the control group and in all experimental groups. The low content of connective tissue and the high ratio of bone tissue indicated more active osteogenesis processes and reparative regeneration in comparison with other groups.

Role of antimicrobial peptides system in inflammatory periodontal diseases non-specific oral cavity protection.

The system of antimicrobial peptides (AMP) is one of the most ancient mechanisms of the macroorganism resistance to infectious pathogens invasion. The aim of the study was to determine the role of the antimicrobial peptides system and periodontal pathogenic markers in the development and progression of inflammatory periodontal diseases. Gingival pocket washes (91 samples in total) for the research were received from patients with inflammatory periodontal diseases (chronic periodontitis and gingivitis) and intact periodontium. Using ELISA, the content of antimicrobial peptides was determined: human alpha-defensin (HNP 1-3), beta-defensin (HBD 1-3) and cathelicidin (LL-37). Periodontal pathogenic markers were isolated during RT-PCR. The study revealed differences in AMP concentrations by groups: level of HBD 2 in patients with chronic periodontitis was 1,36 times higher than those in the group of patients with chronic gingivitis (p=0,023) and 2,39 times higher than those in the control group (p<0,001), the content of HNP 1-3 in the group of patients with chronic periodontitis was reduced by 1,23 times compared with the indicators of the group of patients with gingivitis (p=0,045) and by 1,97 times compared with the indicators of the control group (p<0,001). The frequency of detection of periodontal pathogenic bacteria genes was 88,0% in patients with periodontitis, 76,92% in patients with gingivitis and 33,3% in the group with intact periodontium. HBD 2 content moderately correlated with the definition of P. gingivalis (r=0,612; p=0,022), T. forsythensis (r= 0,434; p=0,015), A. actinomycetemcomitans (r=0,483; p=0,006), a moderate negative correlation was detected between the content of HNP 1-3 and the release of periodontal pathogens in associations (P. gingivalis with T. forsythensis and T. denticola) (r=-0,388; p=0,031) in the group of patients with chronic periodontitis. Thus, the revealed relationships and correlations indicate shifts in the processes of reparative regeneration of the oral cavity and the regulation of local immunity in response to microbial invasion.

The effect of cyclic polychemotherapy on the morphofunctional state of the gonads

Aim. The analysis of scientific publications on the treatment of malignant neoplasms, the effect of antitumor therapy on the morphofunctional state of the gonads is carried out.Results. Treatment of malignant neoplasms is often accompanied by side effects that directly depend on the patient’s age, type of cancer, treatment regimen and doses, which has put forward a new urgent problem – the state of health and quality of life during remission of cancer or after recovery from it. Thus, cytostatically induced testicular damage leads to reproductive dysfunction in men on the “pre-testicular” (central nervous system and the peripheral nervous system, pituitary gland), “testicular” (gonads), “post-testicular” (epididymis, etc. organs of the genitourinary system involved in spermogenesis) levels of the reproductive system, which is especially important against the background of a sharply declining fertility of the modern male population. Accordingly, understanding the regularities of the processes of reparative regeneration of damaged tissues is important for the development of rehabilitation programs, the preservation of reproductive function and quality of life in patients who have undergone cytostatic therapy, especially in young people.Conclusion. The literature review covers epidemiological and experimental data on the effects of chemotherapy on spermatogenesis.