PROTEOLYTIC SYSTEM CONDITION AS IN THE CASE OF NEUTROPHIL ELASTASE IN PATIENTS WITH TROPHIC ULCERS ON THE BACKGROUND OF DIABETES MELLITUS.

Relevance . According to the WHO and the International Diabetes Federation (IDF), the number of patients with diabetes in the world reached 463 million people in 2019. A typical manifestation of complications of diabetes mellitus is the development of trophic ulcers of the lower extremities, which leads to poor quality of life, disability, and high financial costs for treatment Objective. To study the effect of autogenic platelet-rich plasma (APRP) on fluctuations of neutrophil elastase level in patients with trophic ulcers on the background of diabetes mellitus, which may help influence the pathogenesis of ulcer formation in DFD. Materials and methods. Ninety-eight at Sumy 20 To obtain objective, we investigated the study took minutes. Conclusions. study nmol/(min • In patients of the comparison group, the elastase level decreased to 164.17±2.00 nmol/ min • mL. The decrease in neutrophil elastase levels in the main group occurred significantly faster than that in the comparison group, which indicated a positive effect of autogenic platelet-rich plasma on the corresponding link in the pathogenesis of ulcerative defect.


Introduction
Diabetes mellitus is one of the most important medical and social problems of nowadays that affects most economically developed countries in the world. According to WHO and the International Diabetes Federation (IDF), the number of patients with diabetes in the world reached 463 million people in 2019, and up to 2045, this number may increase to 700 million people. One-third of them are senior people -over 65 years of age, which is evidence of limited use of surgical methods of treatment in them. In 2019, 760 billion US dollars were spent on the treatment of diabetes mellitus and its complications worldwide. [1]. One of the most severe local complications of DM is diabetic foot syndrome [2]. It typically manifests with the development of trophic ulcers of the lower extremities, which leads to poor quality of life, disability, and high financial costs for treatment [3].
Proteolysis processes occupy a significant place in the processes of ulcer formation, namely in the reactions of inflammation and tissue destruction [4]. Neutrophil elastase (NE) is known to be the main representative of this system. Recently, a number of scientific papers have been devoted to the study of this enzyme and have proven an increase in the level of neutrophil elastase (NE) activity in various pathological conditions [6]. A significant part of these works was aimed at studying cystic fibrosis, acute respiratory distress syndrome, arterial hypertension, bronchiectasis, chronic obstructive pulmonary diseases, bullous emphysema, spontaneous pneumothorax, pulmonary and pleural tuberculosis, and acute appendicitis. [5,6,7,8]. The proteolytic system state in patients with trophic ulcers of diabetic origin and the NE changes remain poorly studied.
It was found that the predominant amount of elastase is formed in neutrophils, which release elastase after its activation. After release, elastase participates in the lysis of matrix proteins, mainly elastin, collagen, fibronectin, proteoglycans, accompanied by the destruction of the stroma of the affected organ up to the formation of destructive processes [9].
Thus, neutrophil elastase plays a leading role in inflammatory processes and tissue destruction, regardless of their etiology. Taking this into account, the study of the peculiarities of proteolysis in ulcerative processes of the lower extremities as in the case of neutrophil elastase and fluctuations in its level during treatment determines the relevance of the problem, which is of theoretical and practical interest.
Objective: to study the effect of autogenic platelet-rich plasma (APRP) on fluctuations in neutrophil elastase level in patients with trophic ulcers on the background of diabetes mellitus, which may help influence the pathogenesis of ulcer formation in DFD.

Materials and methods
The study was conducted at the Burn Department and the Vascular Surgery Department of Sumy Regional Clinical Hospital. Ninety-eight patients with neuropathic ulcers of diabetic origin were examined and treated. Patients were divided into two groups. The comparison group (Group II) included 47 patients who received standard treatment according to the recommendations of the International Working Group on the Diabetic Foot (IWGDF 2015), which included: wound management (treatment of ulcers with antiseptic solutions, necrectomy), correction of carbohydrate metabolism (hypoglycemic drugs), antibiotic therapy, foot pressure offloading with orthopedic insoles. The main (Group I) included 51 patients who had the standard treatment supplemented with APRP according to our proposed method, i. e. by administration along the periphery of the trophic ulcer and local APRP applications. The control group included 20 practically healthy people. To obtain the objective, we investigated the changes in elastase levels during the treatment. Fifty-one people were observed in the main group, and 47 people were observed in the comparison group.
On the day of hospitalization and on day 20, 5 ml blood samples were drawn from the ulnar vein. Further research was performed according to the well-known scheme, based on centrifugation at 1500 rpm for 20 minutes. The research took 25 -30 minutes [10,11].

Results and discussion
During the study of neutrophil elastase in patients with neuropathic ulcers of diabetic origin, it was found that the level of neutrophil elastase in patients of both groups was increased on the day of hospitalization. Thus, in patients of the main group, the average level was 272.4 ± 4.2 nmol/min • mL, and in patients of the comparison group, it was 274.2 ± 3.2 nmol/min • mL, which was 3.8 times higher than in the control group (71.2 ± 3.7). The results are presented in Table 1. On the background of significant clinicalmacroscopic improvement, accompanied by a decrease in edema and hyperemia, ulcer clearing, and improvement of the general condition, the level of NON-venous blood in the main group decreased to 93.24±1.78 nmol/min • mL, and remained 1.3 times higher than that in the control group. In patients of the comparison group, the elastase level decreased to 164.17±2.00 nmol/min • mL and remained 2.3 times higher than the level in the control group. That is, the decrease in NE level in the main group occurred much faster than in the comparison group, which indicated the effect of APRP on the corresponding link in the pathogenesis of ulcerative defect.

Conclusions
In trophic ulcers of the lower extremities on the background of diabetes mellitus, there is an imbalance of the proteolytic system, namely, an increase in the level of neutrophil elastase in the blood serum. During the study, it was found that the level of neutrophil elastase in patients of the main group was in the range of 268-276 nmol/(min • mL), and the average level of the enzyme was 272.4 ± 4.2 nmol/(min • mL). The neutrophil elastase level in patients of the comparison group was in the range of 269-279 nmol/(min • mL), and the average level of the enzyme was 274.2 ± 3.2 nmol/(min • mL). The levels in both groups were 3.8 times higher than that in the control group (p<0.05).
During 20 days after treatment, the level of elastase remained 1.3 times higher in the patients of the main group as compared to the control levels, while in the comparison group, the decrease in elastase levels was significantly lower, remaining 2.3 times higher as compared to the control level. Thus, the positive effect of APRP on the proteolytic link (neutrophil elastase) in the pathogenesis of ulcerative defect has been proved.