HMGB1-Mediated Activation of the Inflammatory-Reparative Response Following Myocardial Infarction

Different cell types belonging to the innate and adaptive immune system play mutually non-exclusive roles during the different phases of the inflammatory-reparative response that occurs following myocardial infarction. A timely and finely regulation of their action is fundamental for the process to properly proceed. The high-mobility group box 1 (HMGB1), a highly conserved nuclear protein that in the extracellular space can act as a damage-associated molecular pattern (DAMP) involved in a large variety of different processes, such as inflammation, migration, invasion, proliferation, differentiation, and tissue regeneration, has recently emerged as a possible regulator of the activity of different immune cell types in the distinct phases of the inflammatory reparative process. Moreover, by activating endogenous stem cells, inducing endothelial cells, and by modulating cardiac fibroblast activity, HMGB1 could represent a master regulator of the inflammatory and reparative responses following MI. In this review, we will provide an overview of cellular effectors involved in these processes and how HMGB1 intervenes in regulating each of them. Moreover, we will summarize HMGB1 roles in regulating other cell types that are involved in the different phases of the inflammatory-reparative response, discussing how its redox status could affect its activity.

Impact of post- amputation pain syndrome on the results of bone stump formation

Background. To the present day, a high rate of unsatisfactory amputation results still exists. The healing of the bone residual limb, the main support element of the residual limb, is of particular importance. Objective. To study the impact of postamputation pain syndrome on the nature of reparative processes in the bone residual limb. Methods. Three series of experiments were performed on 45 rabbits, 15 in each with mid-third thigh amputation and muscular plasty. In series 1 and 2, a perineural catheter was attached to the sciatic nerve stump during amputation, and mechanical irritation of the nerve was performed daily for 20 minutes in series 1 for 20 days. In series 2, 0.3 ml of 1% lidocaine was injected through the catheter into the circumference of the nerve twice daily for 20 days. Animals of series 3 served as a control. The follow-up periods were 1, 3, 6 months. The study method was histological with infusion of the vessels with ink-gelatin mixture. Results. In series 1, there was a sharp disturbance of the reparative process, which consisted in shape changes, resorption of the cortical diaphyseal plate, stump deformity, absence of bone closure plate formation, and microcirculatory disturbances. In most experiments of the 2nd series, organotypic stumps were formed with normalized microcirculation. In series 3, the results of the residual limb formation were better than in series 1, but worse than in series 2. Conclusion. In the absence of pain syndrome, the bone stump after amputation at the diaphysis level over a period of 1, 3, 6 months retains its cylindrical shape, the structure of the cortical diaphyseal plate, the content of the medullary canal with normal microcirculation, the formation of the bone closure plate, and the completion of the reparative process. The presence of postamputation pain syndrome in the stump distorts the course of the reparative process with the development of pathological remodeling of bone tissue.

Notum Protects Against Myocardial Infarction-Induced Heart Dysfunction By Alleviating Cardiac Fibrosis

Cardiac fibrosis is a pathological reparative process that occurs subsequent to myocardial injury. It is associated with cardiac systolic and diastolic dysfunction and reduced cardiac compliance that eventually leads to heart failure. Delaying or inhibiting the progression of pathological myocardial fibrosis is of great significance for the treatment of many cardiovascular diseases. The Wnt signaling pathway is closely related to the occurrence of organ fibrosis, and Notum is a highly conserved secreted feedback inhibitor of Wnt signaling. It has been shown that Notum acts as a regulator in many organs, such as the aging intestinal epithelium, adult ventricular-subventricular zone neurogenesis, and mouse tooth root development. However, the role and mechanism of Notum on cardiac fibrosis are not well-understood. In this study, we found that Notum significantly increased survival rate and improved cardiac function following myocardial infarction in mice. More importantly, Notum inhibited the Wnt/β-catenin signaling pathway and senescence of cardiac fibroblasts, thereby decreasing the activation of cardiac fibroblasts, reducing the excessive deposition of extracellular matrix, and ultimately inhibiting the occurrence of cardiac fibrosis. Taken together, our findings demonstrated the anti-fibrotic effects of Notum on maladaptive cardiac fibrosis, and suggest that it may be a new strategy for the treatment of cardiac fibrosis.

Evaluation of Two Different Types of Mineral Trioxide Aggregate Cements as Direct Pulp Capping Agents in Human Teeth

Traumatic human dental injuries involving the pulp might necessitate direct capping procedures. This clinical study aimed to analyse the histological outcomes using two different direct capping materials. Twenty patients with bilateral premolars, scheduled for orthodontic extraction, were selected. The teeth were treated either using ProRoot MTA or RetroMTA. All patients were recalled after 30 and 60 days for teeth extraction. The histopathologically stained specimens were blindly evaluated using hard tissue bridge formation, inflammatory reaction and pulpal findings criteria. Data were evaluated statistically. Results: After 60 days, only the parameter for hard tissue bridge formation showed significant difference in the ProRoot MTA group (p = 0.010), while both direct capping materials performed similarly regarding inflammatory pulp reaction and pulpal findings. Although, during the first 30 days, RetroMTA presented better results in terms of continuity, morphology, hard tissue bridge localisation, and extension/general state of the inflammatory reaction, the continuity was better at 60 days when ProRoot MTA was applied. Treatment with RetroMTA healed the pulpal tissue faster compared with ProRoot MTA but it seemed to be rather a reparative process.

PECULIARITIES OF PERFORMING ORGAN-SAVING AMPUTATION OF THE FOOT COMBINED WITH OZONE THERAPY, LOCAL APPLICATION OF AUTOLOGOUS PLATELET-RICH PLASMA AND VACUUM SANATION OF POSTOPERATIVE WOUND IN PATIENTS WITH ISCHEMIC-GANGRENOUS FORM OF DIABETIC FOOT SYNDROM

A positive result of treatment of patients suffering from ischemic-gangrenous form ofdiabetic foot syndrome (DFS) becomes possible with an optimal choice of surgery,effective renewal of blood supply and active stimulation of tissue restoration processon the cellular level.Objective – to study efficiency of the suggested organ-saving variant of surgery combinedwith the use of a complex of auxiliary factors of a reparative process activation in thewound including regional ozone therapy, vacuum sanitation and local application ofautologous platelet-rich plasma (PRP).Material and methods. The treatment of 210 patients with ischemic-gangrenous formof diabetic foot syndrome was carried out from 2017 to 2020. The efficiency of one ofthe variants of organ-saving operative intervention was studied. In the control group -104 (49.52%), the treatment was carried out in accordance with the standard scheme.In the main group (106 patients - 50.47%), in addition to the standard scheme, regionalozone therapy, vacuum sanitation and local application of autologous-rich plasma(PRP) were carried out.Results. These measures reduced the period of treatment of patients in the hospital to24 ± 1.2 days in the main group compared to 37 ± 2, 4 in the control one. 2 years later, patients of the main group confirmed the formation of a foot stumpfunctionally adapted for walking with angular dislocation of fragments of the cuboidand scaphoid bones.Conclusions. The suggested modification of the organ-saving and partial foot amputationin patients with IV degree of ischemia and DFS is indicative of a possibility to performsuch kind of surgery as a variant of choice for patients with ischemic-gangrenousform of diabetic foot syndrome. The complex of auxiliary measures (regional ozonetherapy, vacuum sanitation and local administration of autologous platelet-rich plasma(APRP)), activates a reparative process of healing of a chronic foot wound whichenables to make the period of hospital staying for patients shorter – to 24±1,2 days inthe main group as compared to 37±2,4 days in the control one. Clinical observation ofa remote postoperative period (2 years later) confirms a possibility to form a foot stumpfunctionally adapted for walking with angular dislocation of fragments of the cuboidand scaphoid bones, functionally advantageous for supporting load.

Features of organ-saving foot amputation associated with ozone therapy, local application of autologous platelet-rich plasma and vacuum sanitization of postoperative wound in patients with ischemic-gangrenous form of diabetic foot syndrome

Improvement of reparative process of the chronic wounds with the insufficiency of peripheral blood suppling in patients suffering from diabetes mellitus is an important issue requiring further investigation. An optimal choice of surgery, effective renewal of blood supply and active stimulation of tissue repair on the cellular level are essential components of success treatment of this problem.Objective of research: From 2017 to 2020, the efficiency of one of the variants of organ-saving surgery performed on 210 patients with an ischemic-gangrenous form of diabetic foot syndrome was studied.Materials and methods. Control group included 104 patients (49.52%), were the treatment carried out in accordance with the standard scheme. The main group (106 patients - 50.47%) in addition to the standard therapy have used regional ozone therapy, vacuum sanitization and local application of autologous platelet-rich plasma (APRP).Results. These proposed measures reduced the period of clinical treatment to 24±1,2 days in the main group compared to 37±2,4 in the control one. 2 years later, patients of the main group confirmed the formation of a foot stump functionally adapted for walking with angular dislocation of fragments of the cuboid and scaphoid bones.Two years after foot amputation due to the ischemic-gangrenous form of diabetic foot syndrome (DFS), the amount of repeated above knee amputations was 1.8 times higher in the control group in comparison with the main group, which is indicative of a reasonable use of the complex of activate a reparative process in the wound.Conclusions: The suggested modification of the organ-saving and partial foot amputation in patients with IV degree of ischemia and DFS is indicative of a possibility to perform such kind of surgery as a variant of choice.The complex of proposed additional measures including regional ozone therapy, vacuum sanitization and local administration of autologous platelet-rich plasma activates a reparative process of a chronic foot wound and promotes an effective treatment of patients with ischemic-gangrenous form of DFS.

Matrix metalloproteinases in children with uncomplicated compression fractures of the spine

The aim of the study was to determine changes in the content of matrix metalloproteinases (MMP) and their tissue inhibitor in children with uncomplicated compression fractures of the spine (UCFS). Materials and methods. Eighty-five children, including 69 patients with UCFS (average age 12.3 ± 2.6 years), were comprehensively examined. The reference group consisted of 16 children (average age 11.8 ± 2.7 years) without spinal pathology. During the diagnostic period for 1-3 days, changes in the MMP content and their tissue inhibitor (TIMP-1) in blood serum were determined by the enzyme immunoassay method in all children after trauma. Results. It was found that in the acute period after spinal injury, the blood levels of gelatinases (MMP-2 and MMP-9), stromelysin (MMP-3), and collagenases (MMP-8) significantly increased compared to their levels in children of the reference group. At the same time, the levels of TIMP-1 and the ratio of MMP/TIMP-1 concentrations in the blood of patients with UCFS significantly decreased compared to the control, which indicates the predominance of the proteolytic effect of MMP. Analysis of changes in the content of MMP in the blood in UCFS boys and girls did not reveal significant differences in the levels of the studied MMP and TIMP-1, except for a significant increase in the concentrations of stromelysin (MMP-3) in the blood serum of boys compared with its level in girls and the control. With different severity of the course of UCFS in children, a significant increase in MMP concentrations associated with an increase in the severity of the injury was revealed, and a substantial decrease in the content of TIMP-1 in the blood of patients compared to its levels in children with 1-2 degrees of severity and control. Conclusion. The established patterns indicate that the determination of the content of MMR and TIMP-1 in the blood in UCFS children allows monitoring the course of the reparative process after injury to the vertebral bodies in children.

Biocompatibility of implants in planned and urgent hernia surgery

The aim of the work – to analyze modern scientific and practical achievements in the effectiveness of implants in planned and emergency hernia surgery and to identify promising areas for further research. The literature review presents modern views on the assessment of biocompatibility, effectiveness and appropriateness of the use of implants in planned and urgent hernia surgery. The importance of determining the main factors of ventral hernia occurrence, assessing the prognostic components of the reparative process course in the field of hernioplasty and methods of correction has been substantiated. Physicochemical characteristics of implants, which both historically and on an up-to-date level are used according to planned or urgent conditions for performing surgical intervention in patients with ventral hernias, are given. The necessity of using an integrated approach to choosing a method for correction or reconstruction of the abdominal wall, taking into account the biological and dynamic conditions of its state, is shown. The need for a selective approach to the choice of therapeutic tactics in patients, especially if hernia repair is necessary in conditions of a clean-contaminated or infected surgical wound, is emphasized. Conclusions. In order to improve the consequences of hernioplasty, it is necessary to assess patient's reserves and risks more thoroughly and comprehensively, as well as to make absolute indications for the use of implants. An improvement in the results of urgent and planned repair of ventral hernias is to perform surgical interventions only in surgery departments constantly provided with modern world achievements.

Investigation of sanogenesis in hip fracture-dislocation

Background. The background of the injured hip joint is determined by the course of the reparative process, which, in turn, depends on the changes occurring in the body of the injured at the local and systemic levels as a result of trauma and further therapeutic measures. The purpose of the work is to identify the directions of sanogenesis of fracture-dislocations in the hip joint, which determine the changes resulting from trauma in the victim’s body and influence the choice of treatment tactics, the course of the reparative process in the damaged joint, the content and results of complex restorative treatment. Materials and methods. There were examined 180 patients with hip fracture-dislocations using the clinical, radiological, laboratory methods, methods of conceptual and mathematical modeling, statistical method. Results. The planning of treatment tactics should be approached from the standpoint of analyzing different mechanisms of pathogenesis after traumatic arthrosis by determining the factors of destruction and their role in the sanogenesis of traumatic injuries of the hip joint. Based on the study of biomechanical changes, the characteristics of the immune status and metabolic processes in the body of the victims, their relationship with the clinical, radiological, and morphological changes in the area of damage, a conceptual position regarding the treatment are proposed. The most significant factors that determine the course of the recovery processes are highlighted: structural damage to the cartilage covering, acetabular subchondral bones and the head of the femur; damage to the articular bag of the hip joint; damage to the muscles of the pelvic girdle; changes in the stress-strain state in the hip joint; violation of the stability of the damaged hip joint; local post-traumatic osteoporosis; reactive inflammation in the damaged joint; regeneration of the connective tissue in the damage focus; pathogenic factors due to treatment. The priority directions for solving the problem are to improve the diagnosis of fracture-dislocations in the area of the hip joint and to study pathological changes in the body of victims in different periods after trauma to substantiate the criteria for a differentiated approach to the choice of treatment tactics. The directions and content of pathogenetic treatment of hip fracture-dislocations depend on the type of damage to the hip joint and the duration of the injury. Conclusions. The main points of the treatment program for fresh injuries are the elimination of hip dislocation, restoration of stability of the hip joint, optimization of the mode of functional unloading of the joint, functional rehabilitation treatment, drug correction of the reparative process.

CLINICAL AND MORPHOLOGICAL FEATURES OF ACUTE AND CHRONIC WOUNDS

Background. The chronicity of the wound is a factor leading to a greater number of postoperative complications when performing plastic closure of wound defects and requires the use of special methods of preoperative preparation. In clinical practice, it is important to use precise clinical and morphological criteria to assess the activity of the inflammatory response and the degree of impairment of the proliferative phase of the reparative process. Aim. To determine the features of clinical parameters of the local status of wound defects and their correspondence to morphological criteria in patients with acute and chronic wounds of various genesis. Material and Methods. Clinical signs of acute and chronic wounds in 26 patients with different types and duration of integumentary tissue defects were described. In a hospital setting, a morphological study of the biopsy specimens from wounds and surrounding tissues was performed to identify histological signs of chronic wound healing. The correspondence between clinical and morphological signs of acute and chronic wounds was analyzed. Results. The initial study of the local status of wound defects did not reveal significant differences in the clinical signs of acute and chronic wounds. Histological examination of the wound biopsy specimens revealed morphological signs of chronic wound healing. Conclusion. Evaluation of clinical signs of the local wound status is necessary to identify the dynamics of wound parameters during treatment. Histological examination of wound biopsy specimens makes it possible to more reliably identify signs of chronicity of the wound.