Morphological Aspects of Reparative Bone Tissue Regeneration under the Influence of Antitumor Chemotherapy

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

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.

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.

THE EFFECT OF ENTEROSORPTION AND INTRATISSULAR ELECTROFORESIS OF ANTIBACTERIAL DRUGS ON PROGRESS OF BURN DISEASE

Summary. The purpose of the research was to explore the appropriateness of combined usage of enterosorption amplification and intratissular electrophoresis (ITE) of antibiotics in injured with the substantial thermal burns. Clinical effect of the enterosorbtion and ITE antibacterial drugs in burn disease cases was studied in 26 patients with superficial and deep dermal burns (IIb-III deg.) from 27 to 60 % of their body surface. Enterosgel was prescribed from 3rd day after injury for 15–20 g 3–4 times a day for 7–14 days. ITE of antibiotics conducted from the 3–4 day by the «Поток-1» device, applying the direct current with density 0,03-0,05 mAh/cm2 for 60 min. Materials and methods. The authors studied the leukocyte reaction by a general blood test. The degree of intoxication was determined by the level of molecules of average mass and blood plasma electrical conductivity. They evaluated the dynamics of the wound process, conducted bacteriological and cytological researches of the burn wounds in dynamics on 1–3, 6–7, 13–14, and 19-21 days after traumatization. Results and discussion. This treatment tactic allows to reduce the level of endogenous intoxication, to optimize the course of the wound process in the area of thermal damage, to intensify demarcation-cleansing processes and reparative regeneration, which increases the clinical effectiveness of treatment. Conclusions. As a result of the research, it was found that the combined usage of enterosorption detoxification by enterosgel and ITE of antibacterial drugs in the complex treatment of victims with widespread burns is appropriate and justified.

Bone Remodeling Markers in Assessing of Sternal Reparative Regeneration in Patients With Carbohydrate Metabolism Disorders After Coronary Bypass Surgery

Aim To study time-related changes in bone remodeling markers in patients with ischemic heart disease (IHD) associated with type 2 diabetes mellitus (DM) and disorders of carbohydrate metabolism (CM). Also, a possibility was studied of using these markers for evaluation of breast bone reparative regeneration in early and late postoperative periods following coronary bypass (CB).Materials and methods This study included 28 patients with IHD and functional class II-III exertional angina after CB. Patients were divided into 2 groups based on the presence (group 1) and absence (group 2) of CM disorders. Contents of osteocalcin (OC), C-terminal telopeptide (CTTP) of type 1 collagen, deoxypyridinoline (DPD), and alkaline phosphatase bone isoenzyme (ALPBI) were measured by enzyme immunoassay on admission (Т1) and at early (Т2) and late (Т3) postoperative stages. Sternal scintigraphy with a radiopharmaceutical (RP) was performed at stage 3 following sternotomy.Results The content of OC and CTTP was reduced in group 1 compared to the values in the group without CM disorders (р<0.005) at stages Т1 and Т2. There were no significant intergroup differences in concentrations of ALPBI and DPD throughout the study. Time-related changes in OC, CTTP, and DPD had some intergroup differences: the increase in biomarkers was observed in group 1 considerably later, at stage Т3 (р<0.005), while in group 2, it was observed at stage T2 after sternotomy. Scintigraphy revealed significant intergroup differences in the intensity of RP accumulation in sternal tissue.Conclusion The intergroup differences in the content of biomarkers evidenced a disbalance among processes of formation and resorption of bone tissue and delayed remodeling processes in patients with IHD associated with type 2 DM and CM disorders. The study confirmed significance of comprehensive evaluation of time-related changes in markers for bone tissue metabolism and sternal scintigraphy for diagnosis and evaluation of sternal reparative regeneration following sternotomy in patients with IHD associated with type 2 DM and disorders of CM metabolism.

BIOMECHANICAL FACTORS IN RESIDUAL LIMB FORMATION AFTER AMPUTATION

The aim: To study the influence of biomechanical factors on the character of morphological disorders in the process of reparative regeneration at the end of the residual limb after amputation. Materials and methods: 10 series of experiments on 144 rabbits were conducted. We used myodesis with normal, insufficient and excessive muscle tension, their electrical stimulation, tight and leaky closure of the bone marrow canal. Terms of observation 1, 3, 6 months. The method of research – histological with the filling of vessels with inkgelatin mixture. Results: Dense closure of the meduallary cavity and uniform muscle tension during plasty in the first three series of experiments allow to obtain a cylindrical residual limb with preservation of the cortical diaphyseal plate, formation of the bone closing plate, normalization of intraosseous microcirculation, completion of the reparative process. In the majority of observations of the IV-X series there was a reparative regeneration disorder connected with the incorrect tension of muscles and the absence of normalization of intraosseous circulation, the reparative process was not observed to be complete, which led to the pathological reorganization of bone tissue with the formation of stumps of various shapes. Conclusions: Uneven muscle tension and lack of closure of the intramedually canal except for microcirculation disorders leads to increased periosteum bone formation, formation of periosteum cartilage exostases, clavate stumps, resorption and fractures of the cortical diaphyseal plate with curvature and stump axis disorders, formation of a conical stump.

New strategies in bone tissue regeneration via application of magnetomechanical transduction

Reparative regeneration is one of the key problems in traumatology and orthopaedics. Despite the fact that bone regeneration is a self-regulatory physiological process of bone formation, complex clinical conditions require additional enhancement of bone regeneration – either local or systemic. This review provides a concise description of main stages of reparative regeneration. The search was performed in PubMed and e-LIBRARY databases among papers published between 2000 and 2021. Main strategies presently used for acceleration of bone tissue regeneration and limitations of their application are presented. This review gives a detailed description of one of the most promising means for bone tissue regeneration enhancement. Namely, magnetomechanic transduction of magnetic nanoparticles using functionalised targeted agents in an alternating magnetic field that induces osteogenic differentiation of mesenchymal stem cells.

TREATMENT OF ODONTOGENIC PHLEGMONS IN PATIENTS TAKING INTO ACCOUNT THE BIORITHM OF LIFE

The aim: Of our study was to establish how the biological rhythm of human affects the reparative functions of the body in terms of odontogenic purulent-inflammatory diseases of the maxillofacial localization. Materials and methods: The research was conducted on the basis of the Department of Maxillofacial Surgery on the basis of «Poltava Regional Clinical Hospital. M.V. Sklifosovsky». A total of 40 patients with odontogenic phlegmons of maxillofacial localization. Results: On the first day of the study, the indicators of the clinical condition of patients did not have a significant difference in all study groups. On the 3rd day of all studied groups, the number of points probably decreased compared to the first day of the study by 22.5%, 23.1%, 23.7%, 22.7%, respectively. On day 5, we have observed a significant difference between the previous results in all groups: 1a - 26.6%, 1b - 23.8%, 2a - 23.9%, 2b - 24.0%. Conclusions: The most effective treatment results were observed in patients of the morning chronotype who underwent surgery in the morning. Thus, the influence of the morning chronotype of the circadian rhythm on the course of reparative processes is manifested in the later stages of reparative regeneration.