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ENGLISH VERSION: THE USE OF DRUGS WITH SODIUM HYALURONATE IN
_ _ _ _ _ _ _ _ *
COMPLEX TREATMENT OF PATIENTS WITH CHRONIC FRONTAL SINUSITIS*
Loburets A.V.1, Neporada K.S.2, Bezshapochniy S.B.1
Higher State Educational Establishment of Ukraine "Ukrainian Medical Stomatological Academy",
1 Department of Otorhinolaryngology with Ophthalmology
2 Department of Medical, Bioorganic and Biological Chemistry
Topicality: result of surgical treatment depends on the chosen method of postoperative period and the main role is the decrease of consequences of surgical trauma. Despite the wide range of drugs for local and systemic use the question of pharmacotherapy of operated sinus has not been decided yet. Safety and high clinical efficacy are the main peculiarities of modern drug. Recently doctors are interested in the use of drugs with hyaluronic acid. The aim is to investigate the ciinical efficiency of drugs with hyaluronic acid in the treatment of chronic frontal sinusitis. Materials and Methods: Surgical treatment of 30 patients with chronic frontal sinusitis was done. Patients were divided into 2 groups based on postoperative period: I (n = 15) had traditional therapy with added hyaluronic acid medicines; II group (n = 15) of patients received traditional therapy that it included nasal cleaning, short course of local decongestants and aqueous salt solutions. For the evaluation of inflammatory-reduction processes in the frontal sinus obtained by washing with saline sodium chloride frontal sinus intraoperatively and then on the fifth day after surgery, proteinase-inhibitory potential, oxidative stress and hexuronic acid content were investigated. Results and discussion: medicines with sodium hyaluronate contribute to the inhibition of oxidative stress in flushing frontal sinus patients with chronic frontal sinusitis, as indicated by a significant decrease of a thiobarbituric acid (TBA-reagents), content of oxidatively modified proteins and the mean mass molecules against the growing activity of catalase and total antitryptic activity than these intraoperational indices and indicators in patients with conventional therapy. Conclusions: based on results of imvestigations it can be recommended the use of gel with sodium hyaluronate for pharmacorrection intraoperatively and during postoperative period to patients who took rhinisurgeries as effective anti-inflammatory and wound-healing agent.
Keywords: frontal sinus, sodium hyaluronate, hyaluronic acid, chronic sinusitis.
Chronic forms of rhinosinusitis are some of the most common diseases in ENT practice. Their incidence of disease in the world ranges widely from 2 to 16% [11] and in recent decades it has grown steadily [5]. Chronic sinusitis composes a serious problem for the healthcare service with treatment-and-prophylactic, scientific and economic points of view [12, 15, 20].
Extra nasal invasive surgical approaches remain dominant despite widespread extension of endoscopic techniques and the introduction of minimally invasive surgical techniques, and today in the treatment of chronic inflammatory disease of the frontal sinus. In most cases, the use is not justified and quite often, in respect that the low level of functionality and trauma, has undesirable clinical consequences, and often requires conduction of reoperations [2, 4].
The result of surgical treatment depends on its correspondence to the established diagnosis, the period of intervention, particularly premorbid condition of the patient and the characteristics of course the disease, technology and the extent of intervention. But clinical experience shows us that a large influence on the outcome of surgical treatment has also a technique of conducting the postoperative period. Its main purpose is to minimize the consequences of surgical trauma, which is associated with morphological and functional changes of the mucous membrane of the nasal cavity and paranasal sinuses, such as swelling and exudation of the tissues, the change in the rheological characteristics of nasal secretion, degeneration and loss of the cilia of the ciliated epithelium, reducing ciliary activity of the ciliated epithelium and, as a consequence, is the long-term impairment of the natural mechanisms of rehabilitation of the upper respiratory tracts [5].
Up to now the issue of effective pharmacotherapy of the operated sinus has not been decided yet despite the
wide variety of drugs for local and systemic use, that have the broad spectrum of clinical effects. The main properties of modern medicine are safety, combined with high clinical efficacy, the possible of maximum coverage of the different stages of the disease. Recently the doctors are interested in the use of drugs based on hyaluronic acid.
Sodium hyaluronate is the sodium salt of hyaluronic acid (HA). Despite the fact that HA was discovered a long time ago, in 1934 and had long-term of the pharmacological and clinical studies, its properties are still actively studied nowadays. Its unique physicochemical and biological properties, including biocompatibility combined with high hydrophilia allow using of HA in various fields of medicine in the form of gels and films. Due to the special molecular structure and a wide range of biological abilities, hyaluronic acid, besides the possibility to induce a direct therapeutic effect, is a natural conduit. Hyaluronic acid provides the transportation of other drugs to the pathological focus. In addition, it also performs the function of control the dosed gradually release of drug from the active area. In the human body hyaluronic acid is a common biological substrate and it is found almost everywhere, and it is one of the major functional components of the intercellular substance [8].
Hyaluronic acid is the only one of glycosaminoglycan, without covalent links with the protein core, there is no proteoglycan of hyaluronic acid. HA molecule consists of repeating units of D-glucuronic acid and N-acetyl-D-glucosamine [6]. HA is present on the entire surface of the respiratory tracts and it is an important component of normal secretions of the mucous membrane and plays a central role in physiological homeostasis of the respiratory apparatus, especially at the level of the upper respiratory tract. In particular, in the mucosa of the nasal
* To cite this English version: A.V. Loburets 1, K.S. Neporada 2, S.B. Bezshapochniy. The use of drugs with sodium hyaluronate in complex treatment of patients with chronic frontal sinusitis // Problemy ekologii ta medytsyny. - 2017. - Vol 21, № 1-2. - P. 9-13.
cavity HA primarily involves in the regulation of vasomotor tone, and the secretion of glands, which contributes greatly to the protection of the mucous membranes, stimulate the activity of ciliated epithelium for the removal of foreign bodies, while preserving the enzymes that are essential for homeostasis of the apical cell surface [22].
Sodium hyaluronate has also been assessed for their properties as anti-adhesive agent in surgery of the vocal cords for the treatment of atrophy of the vocal cords and to reduce postoperative scarring [19]. Sodium hyaluronate has an important role in the functioning of the mucociliary clearance of epithelial surfaces [18], involving in the processes of wound healing and restoration of mucosal surfaces [13], and the viscoelastic support of the state structures that are responsible for speech [9].
Sodium hyaluronate plays a major role in the processes of healing and repairing of damaged mucosal surfaces. Increased expression of sodium hyaluronate was found in the ulcers of the mucosa, where it played the role of ligands for cell adhesion via CD44 epithelial receptors [3, 10].
Thus, the drugs of HA have a marked wound-healing activity, stimulating the migration of fibroblasts and macrophages to the wound surface, as well as proliferative activity. Deposited on the surface of the wound hyaluronic acid does not only create its surface viscous layer with acidic properties, what mechanically isolate it from the external environment, but also has biostimulating effect, forces regenerative processes after traumas and surgical interventions. Medications on the basis of HA contribute to the rapid cleansing of wounds and development of granulation tissue, migration of fibroblasts and macrophages, early epithelialization, thus healing period compared with conventional therapy is reduced [7].
There are studies where it has been proved that sodium hyaluronate significantly improves the temporal indicators of mucociliary clearance compared with saline, indicating an increase in the recovery mucocilary activity after carrying out functional endoscopic sinusotomy. Sodium hyaluronate also reduces the level of rinorea and nasal obstruction, decreases exudation, which has been confirmed by the results of endoscopic studies. These data are confirmation of a study in which the use of sodium hyaluronate for nasal irrigation after endoscopic sinusotomy for rinocerose correction has shown improvement of obstruction of the nose, increase ciliary motility of the ciliated epithelium [17].
The evaluation of current literature has been shown that studies of the properties of HA have the considerable interest worldwide. A number of foreign scientists-clinicians, such as Casale, Gelardi, Soldati, Macchi suggest the need for further study of the properties and clinical effects of hyaluronic acid [14, 17, 21], many of which have not yet been clarified. It is known that studies of the effectiveness of the use of HA in clinical practice are a promising direction of modern medicine.
The aim of the study is to investigate the clinical efficacy of hyaluronic acid in the treatment of patients with chronic sinusitis.
Materials and methods
To achieve this goal, it has been conducted clinical and laboratory studies of 30 patients who took treatment in ENT department of Poltava regional clinical hospital,
who were admitted to hospital for planned surgical intervention for chronic sinusitis.
Criteria inclusion of patients in the study:
• men and women aged from 18 to 65 years old.
• the need for planned surgical intervention (sinusotomy, which included endonasal frontal sinus surgery).
Criteria exlusion from the study:
• The age to 18 years old.
• Acute bacterial rhinosinusitis.
• Allergic forms of rhinosinusitis.
• Polypous rhinosinusitis.
• The presence of concomitant diseases (diabetes, cystic fibrosis, bronchial asthma);
• Growth of the nasal cavity and frontal sinus;
• Pregnancy and breast-feeding.
All examined patients (n=30) were divided into 2 groups. In addition to traditional therapy, the medications based on sodium hyaluronate were administered topically to the patients of the first group (n=15) during surgery and in the postoperative period. The 2nd group (n=15) consisted of patients who in the postoperative period received conventional therapy. All patients of both groups for laboratory studies were taken lavages from the frontal sinus intraoperatively and on the fifth 5 days after surgery.
Traditional therapy included the toilet of the nasal cavity, the local use of topical decongestants in short course (Xylometazoline), irrigation of nasal cavity with water-salt solutions, system application of mucoregulator. If it was necessary, intranasal corticosteroids (Mometasone furoate), was administered to patients in both groups from 10-day postoperative period, which excluded their direct impact on the results of our study.
As pharmacological correction in complex treatment of patients with chronic frontal sinusitis of the 1st group the local medical gel based on sodium hyaluronate (10 mg/ml) and irrigation of the mucous membrane of the nasal cavity and frontal sinus saline containing 0.1% sodium hyaluronate.
The methods of the use of drugs based on sodium hyaluronate which was done to patients of the first group included such elements:
• Intraoperative administration based on sodium hyaluronate (5 ml, 10 mg/ml) by catheter through artificial anastomosis in the region of frontal recess of middle nasal passage;
• Irrigation of mucous membrane of frontal recess and operated frontal sinus by 0,1% solution of sodium hyaluronate twice a day from the second day after surgery.
Preoperative examination included computer tomography, optic endoscopy of nasal cavity and osteomeatal complex, general lab assessments.
Lavages received during irrigation by physiological solution of sodium hyaluronate of operated frontal cavity were taken to examine the condition of repaired processes. Lavages were taken by liquid administration of 5 ml with its aspiration (in 5 minutes) in sterile syringe with frontal sinus.
Lavages from frontal cavity were taken twice:
• During operation, after complete of formation of artificial fronto-nasal anastomosis;
• On the fifth day after postoperative period.
Protein-inhibitory potential was determined in lavages
of frontal cavity and general proteoclastic activity was investigated (A.M. Uholevyi, 1969) and also general
antitryptic activity was also detected (method by K.N. Veremeienko, 1988). Intensity of processes of free-radical oxidation was evaluated based on the content of TBA-reagents (method by I.D. Stalna, 1977), oxidative-modified proteins (method by O. Yu. Dubinina, 2001) and catalase activity (method by M.A. Koroliuk, 1988). The stage of endotoxemia was measured by the content of molecules of average weight (method by N.I. Habriielian,
1984). General content of hexuronic acids by carbazole method was determined (P.N. Sharaiev, 1987).
Results and discussion
It was identified that protein-inhibitory potential of lavage from frontal cavity in patients with chronic frontal sinusitis on the fifth day after surgery significantly changed in the first group of patients who used drugs based on sodium hyaluronate; in patients of the second group changes were not observed (table 1).
Table 1
Indices of proteinase-inhibitory potential in lavage from frontal cavity in patients of different groups (М±m).
Indices The first group (n=15) The second group (n=15)
intraoperatively the fifth day after surgery intraoperatively the fifth day after surgery
General proteoclastic activity, mcM /ml /min 0,024±0,007 0,019±0,010 0,021 ±0,005 0,015±0,021
General antitryptic activity, mcg/ml 15,30±6,08 39,19±9,94* 15,95±6,25 36,06±9,51
Note: * - accuracy of differences between intraoperative indices and
Data which was used after drugs' use based on sodium hyaluronate during complex treatment of patients with chronic frontal sinusitis indicates activation of proteinase inhibitors. This result prevents intensification of proteoclastic processes.
It has been indentified drugs' intake based on sodium hyaluronate after surgery promoted decrease of
on the fifth day after surgery (p<0,05).
oxidative-modified proteins in (5,1), and also promoted decrease the content of mean mass molecules in (2,14) in patients with chronic frontal sinusitis of the first group in comparison with intraoperative indices. There is significant difference (p<0,05) between these indices in the first and the second group on the fifth day of postoperative period (Table 2).
Table 2
es of oxidative stress in patients with chronic frontal sinusitis, (М±m)
Indices The first group (n=15) The second group (n=15)
During surgery The fifth day after surgery During surgery The fifth day after surgery
Activity of catalase, nkat/l 0,69±0,18 1,55±0,23* 0,72±0,19 1,57±0,24*
Content of reactants TEK, mcM/l 72,12±19,27 20,83±8,15* 69,07±18,59 18,03±5,56*
Content of mean mass molecules, RU 0,30±0,05 0,14±0,03** 0,28±0,06 0,25±0,04
Content of oxidative-modified proteins, RU 0,23±0,08 0,035±0,02** 0,21±0,08 0,082±0,02
Note: * - accuracy of differences between intraoperative indices and **- accuracy of differences between indices of the first an
So, treatment of patients with chronic frontal sinusitis with the use of drugs based on sodium hyaluronate promotes inhibition of oxidative stress in comparison with traditional therapy.
On the fifth day after surgery in lavage from frontal cavity in patients of the first group, content of hexuronic acids significantly increased (in 2,8) in comparison with
Indices of hexuronic acidi
in 5 days after surgery (p<0,05).
d the second groups on the fifth day after surgery (p<0,05).
intraoperative index (Table 3). Hexuronic acids (D-glucuronic acid) is one of monomers of disaccharide (hyaluronic acid) (HA). It manifests that sodium hyaluronate stays in the cavity and possibility of its active components in the mucous membrane of frontal cavity increases.
Table 3
s in lavage from frontal cavity in patients with chronic sinusitis (М±m)
Indices The first group (n=15) The second one (n=15)
intraoperatively the fifth day after surgery intraoperatively the fifth day after surgery
Content of hexuronic acids, mcM/l 1,12±0,35 3,18±0,41** 1,04±0,35 1,50±0,39
Note: **- accuracy of differences between of the first and the second
So, it was proved that the use of drugs based on hyaluronic acid in postoperative period promotes more effective treatment and also changes of proteinase-inhibitory potentials and inhibition of development of oxidative stress lead to such results.
No one had side effects which are connected with the use of gel of sodium hyaluronate.
Received data were correlated with results of subjective data (Picture 1) and objective information
oups on the fifth day after surgery (p<0,05).
(Picture 2), received in these patients on the third, fifth, seventh and tenth day after surgery [1]. Subjective assessment was done to study main clinical features, which are present during rhinosinusitis: condition of nasal respiration, presence of local pain and headache. Objective assessment was received to analyze data of endomicrorhinoscopy. Received data manifested by grade scale and they were written in modified scale of endoscopic assessment by Lund-Kennedy [16].
Picture 1. Dynamics of subjective changes in patients of the first and the second groups.
Picture 2. Dynamics of objective changes in patients of the first and the second groups.
So, the use of drugs based on sodium hyaluronate in complex treatment of patients with chronic frontal sinusitis can achieve significant positive dynamics of the main symptoms of this disease.
Conclusions
1. The use of drugs with sodium hyaluronate after surgery in patients with chronic frontal sinusitis promotes more effective treatment in comparison with conventional therapy and it can be manifested by significant increase of general antitryptic activity in the lavage from frontal cavity on the 5th day of postoperative period.
2. Drugs with sodium hyaluronate promote inhibition of oxidative stress in patients with chronic frontal sinusitis, and it can be determined by significant decrease of TBA-reagents content, content of oxidative-modified proteins and mean mass molecules in lavages from frontal cavity based on increase of catalase activity in comparison with intraoperative indices which were received during treatment by traditional therapy.
3. It can be recommended to use gel with sodium hyaluronate for pharmacotherapy intraoperatively and during postoperative period to patients who took rhinosurgeries as effective anti-inflammatory and wound healing substance.
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