Научная статья на тему 'JUSTIFICATIONS FOR DIFFERENTIATED APPROACH IN CORRECTION OF SOME CHANGES OF THE IMMUNOLOGIC DISORDERS IN PATIENTS WITH RAPIDLY PROGRESSING GENERALIZED PARODONTITIS WITH DIFFERENT DRUG SUSCEPTIBILITY OF THE PARODONTAL BACTERIA'

JUSTIFICATIONS FOR DIFFERENTIATED APPROACH IN CORRECTION OF SOME CHANGES OF THE IMMUNOLOGIC DISORDERS IN PATIENTS WITH RAPIDLY PROGRESSING GENERALIZED PARODONTITIS WITH DIFFERENT DRUG SUSCEPTIBILITY OF THE PARODONTAL BACTERIA Текст научной статьи по специальности «Клиническая медицина»

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Ключевые слова
rapidly progressive generalized periodontitis / infectious and inflammatory process / drug-resistant microflora / immunity / швидкопрогресуючий генералізований пародонтит / інфекційно-запальний процес / лікарськорезистентна мікрофлора / імунітет / быстропрогрессирующий генерализованный пародонтит / инфекционно-воспалительный процесс / лечебно-резистентная микрофлора / иммунитет

Аннотация научной статьи по клинической медицине, автор научной работы — A.A. Gudaryan, I.S. Maschenko, A.S. Dorogina, S.V. Shyrinkin

Rapidly progressing generalized periodontitis (RPGP) still remains an extremely important medical problem, despite certain achievements in solving most of the issues of etiology, pathogenesis and treatment. The study included 102 patients with rapidly progressing periodontitis of I-II and II-III degrees of severity, with ineffective and inconsistent results of previous treatment who were examined and treated in the clinic of the Department of Surgical Dentistry, Periodontics and Implantology of the SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine». On the basis of the diagnostic and therapeutic measures carried out, it was established that, in patients with rapidly progressing generalized periodontitis, the formation of various drug sensitivity in periodontopathogenic microorganisms to protocol antibacterial therapy is closely associated with immunological protocol diseases. The presence of drug-resistant bacteria in the periodontal tissues is combined with a more pronounced immunodeficiency in the mechanisms of systemic and local protection than when the lesions are colonized by drug-sensitive periodontal microorganisms. The revealed features of immunity disorders in patients with RPGP with drug-resistant infection to conventional antibiotic therapy are manifested by a decrease in CD3+ lymphocytes, cells with cytostatic activity (CD4+, CD16+) expressing receptors for the activation of lymphocytes CD25+, HLA-DR and apoptosis CD95+), against the background of a slight increase in CD20+, CD116+, CD54+, significant inhibition of the synthesis of SIgA, IgM, a-INF, y-INF; a pronounced increase in the production of proinflammatory cytokines IL-1f and TNF-a. The need for a differentiated approach in the correction of immunological disorders in patients with RPGP depending on the detected sensitivity and resistance of periodontal pathogenic bacteria to the protocol generally accepted antibacterial therapy has been clearly proved; this provides a faster relief of the infectious and inflammatory process (on average on 3.6±0.2 day) in more than 90% of cases, normalization of the parameters of immunological reactivity in 93.3% of the observed and stable clinical remission of the disease.

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Обгрунтування диференційованого підходу в корекції деяких змін імунологічних розладів у хворих на швидкопрогресуючий генералізований пародонтит з різною лікарською чутливістю пародонтальних бактерій

Швидкопрогресуючий генералізований пародонтит, як і раніше, залишається надзвичайно важливою медичною проблемою, незважаючи на певні досягнення у вирішенні більшості питань етіології, патогенезу та лікування. У дослідження було включено 102 хворих на швидкопрогресуючий генералізований пародонтит I-II і II-III ступенів тяжкості, з малоефективними і нестійкими результатами проведеного раніше лікування, які перебували на обстеженні та лікуванні в клініці кафедри хірургічної стоматології, імплантології та пародонтології ДЗ «Дніпропетровська медична академія МОЗ України». На підставі проведених діагностичних і лікувальних заходів встановлено, що у хворих формування різної лікарської чутливості в пародонтопатогенних мікроорганізмів до протокольної антибактеріальної терапії тісно пов'язане з імунологічними захворюваннями. Наявність у тканинах пародонта лікарсько-резистентних бактерій поєднується з більш вираженим імунодефіцитом у механізмах системного й локального захисту, ніж при заселенні осередків ураження лікарсько-чутливими пародонтальними мікроорганізмами. Виявлені особливості порушень імунітету у хворих на швидкопрогресуючий генералізований пародонтит з лікарсько-резистентною інфекцією до загальноприйнятої антибактеріальної терапії проявляються зниженням CD3+ лімфоцитів, клітин з цитостатичною активністю (CD4+, CD16+), що експресують рецептори активації лімфоцитів CD25+, HLA-DR і апоптозу CD95+), на тлі деякого підвищення CD20+, CD116+, CD54+, значним пригніченням синтезу SIgA, IgM, а-ІНФ, уІНФ; вираженим підвищенням продукції прозапальних цитокінів ІЛ-Д і ФНП-а. Наочно доведена необхідність диференційованого підходу в корекції імунологічних розладів у хворих на швидкопрогресуючий генералізований пародонтит залежно від виявлення чутливості і резистентності пародонтопатогенних бактерій до протокольної загальноприйнятої антибактеріальної терапії, що забезпечує більш швидке переривання інфекційно-запального процесу (в середньому на 3,6±0,2 дня) більше ніж у 90% випадків, нормалізацію параметрів імунологічної реактивності в 93,3% спостережуваних і стійку клінічну ремісію захворювання.

Текст научной работы на тему «JUSTIFICATIONS FOR DIFFERENTIATED APPROACH IN CORRECTION OF SOME CHANGES OF THE IMMUNOLOGIC DISORDERS IN PATIENTS WITH RAPIDLY PROGRESSING GENERALIZED PARODONTITIS WITH DIFFERENT DRUG SUSCEPTIBILITY OF THE PARODONTAL BACTERIA»

UDC 616.314-08-039.36:612.017-008-079:579.61:616-078

:579.61:616-078 https://doi.Org/10.26641/2307-0404.2020.4.221409

A.A. Gudaryan, I.S. Maschenko, A.S. Dorogina, S.V. Shyrinkin

JUSTIFICATIONS FOR DIFFERENTIATED APPROACH IN CORRECTION OF SOME CHANGES OF THE IMMUNOLOGIC DISORDERS IN PATIENTS WITH RAPIDLY PROGRESSING GENERALIZED PARODONTICS WITH DIFFERENT DRUG SUSCEPTIBILITY OF THE PARODONTAL BACTERIA

SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine» Oral Surgery, implantology and Periodontology department V. Vernadsky str., 9, Dnipro, 49044, Ukraine

ДЗ «Дн1пропетровська медична академ1яМОЗ Украти»

кафедра xipypzi4H0i стоматологи, ¡мплантологи та пародонтологи

(зав. - д. мед. н., доц. Н.Г. 1дашкта)

вул. В. Вернадського, 9, Дтпро, 49044, Укра'та

e-mail: A.s.dorogina89@gmail.com

Цитування: Медичт перспективы. 2020. Т. 25, № 4. С. 138-146 Cited: Medicni perspektivi. 2020;25(4):138-146

Key words: rapidly progressive generalized periodontitis, infectious and inflammatory process, drug-resistant microflora, immunity

Ключов! слова: шеидкопрогресуючий генерал1зований пародонтит, тфекцтно-запальний процес, лжарсъко-резистентна мжрофлора, iMymmem

Ключевые слова: быстропрогрессирующий генерализованный пародонтит, инфекционно-воспалителъный процесс, лечебно-резистентная микрофлора, иммунитет

Abstract. Justifications for differentiated approach in correction of some changes of the immunologic disorders in patients with rapidly progressing generalized parodontics with different drug susceptibility of the parodontal bacteria. Gudaryan A.A., Maschenko I.S., Dorogina A.S., Shyrinkin S.V. Rapidly progressing generalized periodontitis (RPGP) still remains an extremely important medical problem, despite certain achievements in solving most of the issues of etiology, pathogenesis and treatment. The study included 102 patients with rapidly progressing periodontitis of I-II and II-III degrees of severity, with ineffective and inconsistent results of previous treatment who were examined and treated in the clinic of the Department of Surgical Dentistry, Periodontics and Implantology of the SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine». On the basis of the diagnostic and therapeutic measures carried out, it was established that, in patients with rapidly progressing generalized periodontitis, the formation of various drug sensitivity in periodontopathogenic microorganisms to protocol antibacterial therapy is closely associated with immunological protocol diseases. The presence of drug-resistant bacteria in the periodontal tissues is combined with a more pronounced immunodeficiency in the mechanisms of systemic and local protection than when the lesions are colonized by drug-sensitive periodontal microorganisms. The revealed features of immunity disorders in patients with RPGP with drug-resistant infection to conventional antibiotic therapy are manifested by a decrease in CD3+ lymphocytes, cells with cytostatic activity (CD4+, CD16+) expressing receptors for the activation of lymphocytes CD25+, HLA-DR and apoptosis CD95+), against the background of a slight increase in CD20+, CD116+, CD54+, significant inhibition of the synthesis of SIgA, IgM, a-INF, y-INF; a pronounced increase in the production of proinflammatory cytokines IL-ip and TNF-a. The need for a differentiated approach in the correction of immunological disorders in patients with RPGP depending on the detected sensitivity and resistance of periodontal pathogenic bacteria to the protocol generally accepted antibacterial therapy has been clearly proved; this provides a faster relief of the infectious and inflammatory process (on average on 3.6±0.2 day) in more than 90% of cases, normalization of the parameters of immunological reactivity in 93.3% of the observed and stable clinical remission of the disease.

Реферат. Обгрунтування диференцшованого пщходу в корекщ1 деяких змш ¡мунолопчних розла^в у хворих на шеидкопрогресуючий генерал!зований пародонтит з pi3Horo лжарською чутливктю пародонтальних бактерш. Гудар'ян О.О., Мащенко I.C., Дорогша О.С., Ширшкш С.В. Шеидкопрогресуючий генерал1зований пародонтит, як i ратше, залишаетъся надзвичайно важливою медичною проблемою, незважаючи на певт досягнення у вирШент бшьшост1 питань етюлоги, патогенезу та лкування. У досл1дження було включено 102 хворих на шеидкопрогресуючий генерал1зований пародонтит I-II i II-III ступетв

МЕДИЧН1 ПЕРСПЕКТИВЕ / MEDICNIPERSPEKTIVI

тяжкостI, з малоефективними / нестткими результатами проведеного ранше Л1кування, як! перебували на обстеженн! та лгкувант в КЛ1НЩ1 кафедри х1рург1чно1 стоматологп, /мплантологи та пародонтологИ ДЗ «Дтпропетровська медична академ1я МОЗ Укра'ти». На тдстаег проведених д1агностичних / л!кувальних захоЫе встановлено, що у хеорих формування резноё л1карсько'1 чутливостг в пародонтопатогенних м!кро-органгзмгв до протокольное антибактер1алъно1 терапИ ткно пов'язане з ¡мунолог1чними захворюваннями. Наявтсть у тканинах пародонта л!карсько-резистентних бактерш поеднуетъся з бшьш вираженим Iмунодефщитом у механ!змах системного и локального захисту, тж при заселенн/ осередюв ураження л!карсько-чутливими пародонталъними м1кроорган!змами. Виявлет особливост/ порушенъ ¡мунтету у хеорих на шеидкопрогресуючий генерал!зований пародонтит з л!карсько-резистентною тфекц1ею до загально-прийнятоё антибактер1алъно1 терапи прояеляютъся зниженням СБ3+ лгмфоцитгв, клгтин з цитостатичною активтстю (СБ4+, С016+), що експресуютъ рецептори активаци лгмфоцитгв СБ25+, НЬЛ-БК / апоптозу СБ95+), на тл! деякого П1деищення СБ20+, СБ116+, СБ54+, значним пригн!ченням синтезу SIgЛ, 1^, а-1НФ, у-ШФ; вираженим тдвищенням продукцП прозапалъних цитоютв 1Л-1@ / ФНП-а. Наочно доведена необх!дн1сть диференцшованого тдходу в корекцП 1мунолог1чних розлад1в у хеорих на шеидкопрогресуючий генерал!зований пародонтит залежно в!д виявлення чутливост/ / резистентност/ пародонтопатогенних бактерш до протокольное загалъноприйнятоё антибактер1алъно1 терапИ, що забезпечуе бшьш швидке переривання Iнфекцшно-запального процесу (в середньому на 3,6±0,2 дня) бтъше Н1Ж у 90% випадюв, нормал1зац1ю параметр!в ¡мунолог1чно1 реактивност/ в 93,3% спостережуеаних / стшку клт1чну рем1аю захворювання.

In spite of the seeming decisions for most issues of the etiology, pathogenesis and treatment, rapidly progressing generalized parodontitis (RPGP) still remains an extremely important medical problem associated with a variety of complex tasks and controversial points, which can appear in this pathology and which need a rethinked approach [4, 10, 11].

Now, the only way for the etiotropic treatment of the patients with the rapidly progressive generalized parodontitis with the proven efficiency is the application of antibiotics. However, the experience of many years of the specialists and of the literature data certifies, that an empiric and multiple application of the whole range of antibiotics, included in the multimodality therapy protocol, can lead to the change not only of the microflora's character in the alveolar tissues, but also to promote the drug resistance development to the applicable drugs and to the immune deficiency states. [5, 6, 9]

In that situation, the antibiotic therapy, according to the generally accepted protocol schemes, can be not very effective, what determines the further chro-nization of the inflammatory process in the parodentium and the acceleration of the destructive phenomena in the alveolar tissues, the occurrence of the frequent relapses of active inflammation and the formation of severe variants of generalized parodontitis [2, 7].

It is known, that immunodeficiency states of the local and general immune protection are fundamental in the generalization of the infectious-inflammatory and destructive process in the periodontal complex and in the development of the severe forms of the generalized parodontitis course [3,8].

The matters of choice of suitable immunocor-rectors in the integrated treatment of the rapidly progressing parodontitis with different drug susceptibility of bacterial pathogens remain difficult and not fully studied, what takes on special

significance in the differentiated therapeutic support of such patients.

Taking into account, that one of the key mechanisms in the pathogenesis of development of different drug susceptibility are immunologic disorders of the systemic and local antibody mediated immunity [10], the essential value obtains the dynamic control of immune alterations in process of the complex therapy in the long date after its termination.

All of the above justifies the development of technologies for a differentiated approach in the choice of the necessary correction of immune alterations in patients with the rapidly progressing parodontitis with different drug susceptibility of the parodontal bacteria to the protocol antibacterial therapy, this served as a motive to execute this work and to determine the goal of researches.

Aim of the researche is to improve the quality of the integrated treatment of the rapidly progressive generalized parodontitis in the conditions of the alveolar tissues colonization with the dominant pathogens of disease with different susceptibility to the common protocol therapy.

MATERIALS AND METHODS OF RESEARCH

The research included 102 patients with a rapidly progressing parodontitis of the I-II and II-III severity levels, who were examined and treated in the clinic in the department of surgical dentistry, periodon-tology and implantology of the State Institution "Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine". There were 56 (55%) women and 46 (45%) men in the age from 35 to 50 years (the average age -34.6±1.4 years).

The diagnosis verification was conducted according to the criteria, presented in the classification of I.S. Mashchenko (2003) and in the international classification ICD-10.

The control group was composed of 24 practically healthy donors-volunteers in the age from 35 to 50 years (the average age - 33.8±1.9 years), who did not have pathologies of periodontal tissues, teeth and parodontium injuries.

The research included only the patients with the rapidly progressing generalized parodontitis with low-effective and not constant results of the previously conducted treatment who gave a written informed consent for examination and planning of the therapy measures.

General life history analyses did not detect the coexisting diseases requiring treatment at the moment of examination and the use of antibacterial medications in patients chosen for the in-depth examination.

There were studied general clinical and parac-linical signs and X-ray examination was carried out to receive objective information of the state of the alveolar tissues in patients with the RPGP.

The clinical examination included a detailed collection of complaints and anamnes, a visual and laboratory evaluation of the gingival tissues state, the presence of hyperemia, the degree of bleeding tendency severity of gingival oedema, the depth of the periodontal pockets were determined, their contents and teeth mobility was taken into account.

To conduct the objective characteristics of the state of the alveolar tissues in patients with RPGP, we used the data obtained with the use of the gingival and dental plaque indexes.

The state of oral hygiene in patients was estimated by the methodology of Green V.C. Vermillion (1964), the intensity of inflammatory process and the intensity of the bleeding tendency of the parodontium tissues by Muhlemann H. Co-well (1975), the prevalence rate of inflammation with the papillary marginal alveolar index (PMA), modified by C. Parma in 1960. For objectification of the severity and prevalence rate of the inflammatory and destructive changes in the alveolar tissues, the dental plaque index (PI) by Russel (1956) was used [4].

The depth of the periodontal pockets was measured by the traditional way with Goldman-Fox catheter and according to the data of the graphical cards obtained during the examination of the parodontium tissues by the Florida Probe system.

To clarify the diagnosis and the degree of the destructive process in the osseous structures of parodontium, there was made a dental panoramic radiogram, in the case of necessity - a digital three-dimensional computer dental tomography on the Planmeca Pro Max radial tomograph (Finland).

The results of the clinical and paraclinical studies in patients with the rapidly progressing generalized

parodontitis were compared with the data received from 19 apparently healthy blood donors.

For revealing indicators of the shift of the immune system cellular component (nonspecific resistance system) there was conducted immu-nophenotypic analysis of the state of the subpopulation blood cells composition obtained at determining of the percentage composition of the total number of T-lymphocytes (CD3+), number of T-lymphocytes helpers (CD4+), number of cytostatic T-lymphocytes (CDS+), of the total number of B-lymphocytes (CDi9 +), the content of EK (CD16+), number of a -chains of receptor for the neutrophil chemoattractant factor 2 (CD25+), expressions of Fas-antigen on monocytes (CD95+) and HLA-DR+ cells. The research of the number of the listed cells expressing the antigens was carried out on the fluorescence-based flow cytometry device with monoclonal antibodies of domestic manufacture.

The concentration of cytokines IL-ip, TNF-a, IL-4, INF-a and INF-y was identified by the enzyme-linked immunosorbent assay technique (ELISA) and it was used as the indicating enzyme of the horseradish peroxidase, with the use of testsystems "Protein contour" (city of Saint Petersburg) according to the attached instructions. The results were expressed in pg/ml.

There were detected the levels of concentration of the immunoglobulins SIgA, IgA, IgG and IgM in the oral liquid with the enzyme-linked immunosorbent assay technique with the use of Pro Con set of reagents. The received data were expressed in g/1.

The sensitivity determination of the main periodontopathogenic bacteria to the most widely used in the practical dentistry with antibacterial agents (lincomycin, metronidazole, benzylpenicillin, gentamycine, ampicillin, dioxycycline, erythromycin and Amoxiclav) revealed in the periodontal pockets was conducted with the cassette micromethod. The calculation of results was according to the availability or absence of the bacterial colonies together with the used medication.

The statistical processing of the received data was conducted with Microsoft Excel 2010 (license number 02260-018-0000106-48794) i Statistica 6.1 (serial number AGAR909E415822FA). program with determination of an average (M), standard arithmetic average (m), Student's criterion. The correlation analysis according to Pearson was carried out. To take p<0,05 as the confidence level of the statistical indicators [1].

RESULTS AND DISCUSSION

According to the results of research of sensibility of the periodontopathogenic flora of the alveolar tissues, conducted at the preliminary stage of

observations, it was detected the suppression or absence at all of the drug susceptibility of bacteria, which are widely used in the protocol antibacterial therapy, in more than 70% of patients with rapidly progressive generalized parodontitis with unstable treatment findings. Therewith, the periodontopatho-gens showed themselves as unsusceptible to two and more medications atthe same time.

In estimation of connection of the results of the conducted integrated treatment and of the different drug susceptibility of the separating periodonto-pathogenic bacteria, it was identified the availability of the direct correlation relationship of the unstable results of treatment of the rapidly progressive generalized parodontitis and of the colonization of the alveolar tissues unsusceptible to the protocol antimicrobial therapy (r=89; p<0.05), and with the drug-sensitive periodontopathogens it was marked a highly significant reverse correlation relationship (r=82; p<0.05) of the mentioned bacteria with a short-term disease remission.

Taking into account the abovementioned, it was made a further study of the character of functioning of the local and systemic immunity in patients with stable strains of the parodontal microorganisms to the standard antimicrobial therapy and in patients with highly sensitive bacteria to the traditional medications.

The integrated assessment of the state of immune mechanisms was conducted in patients of two groups, comparable by sexual and age-related principles and by the severity of manifestation of the inflammatory-destructive process in the parodentium, in addition to contamination in the alveolar tissues of drug-sensitive or drug-resistant precursors of disease to the protocol antibacterial therapy, which is a part of the integrated treatment.

The first group (comparison group) consisted of the patients (42 persons) with previous treatment favorable results (long-lasting remission), whose periodontopathogenic bacteria remained highly sensitive to all antibacterial agents, which were used in the integrated protocol treatment of the generalized periodontitis.

The second (principal) group consisted of 60 patients persons with the insufficient results of the previous integrated treatment of progressive generalized periodontitis with stable strains of the periodontopathogenic bacteria to the standard antibiotic treatment (lincomycin and metronidazole).

There are marked disorders of the regulatory relations, in the system of cellular anti-infectious defense, and the signs of a low-grade immune deficiency of the T-cellular immunity according to the received findings in patients with the rapidly progressive generalized parodontitis against the background of

the selected drug-sensible parodontal bacteria to the protocol antibacterial treatment are registered.

On the contrary, in patients with the colonization of parodontium tissues with drug-resistant precursors of disease, the immunophenotypic panel of T-lymphocytes is characterized by a more significant, than in the previous group, decrease of CD3+ and cells with cytostatic activity (CDi6+, CDS+), expression of CD25+, CD116+ cells and apoptosis of CD95+, HLA-DR of molecules (Table 1), this testifies to the availability of the expressed depression of cellular factors of antimicrobial defense by the type of the secondary immunodeficiency in them (Table 1).

The conducted initial researches of the levels of the main immunoglobulins classes in the oral liquid allowed us to detect the presence of the associative relation of different sensitivity of periodontal infection to the standard antibacterial therapy with a certain change of indicators of the local antibody mediated immunity. This regularity is most clearly observed in patients with drug-resistant bacteria, in which there is identified the maximum decrease of SIgA and IgM products in comparison with the parameters of the control group (by 3.9 and 2.6 times, respectively). In addition, within this framework, there was identified the tendency to decrease of IgG and IgA concentration levels only, this indicated the insufficiency of the compensatory response of the local immune anti-infectious defense in the analyzed group under study, most probably, to the antigenic bacterial stimulation: an increase of IgA and IgG synthesis by 17.6% and by 18.2% was noted (Table 1).

By contrast with the patients with the identified drug-sensitive periodontal causative agents, the immunoglobulin products of the main classes (with the exception of SIgA) turned out to be significantly higher than that obtained in the control group, and the synthesis of SIgA decreased only in 2.27 times.

When examining the interferon status, it was detected the impairment of the ability of leucocytes in patients with the rapidly progressing generalized parodontitis to the spontaneous production of INF-a and INF-y in the representatives of both groups. The lowest values of the mentioned cytokines were marked by colonization of the alveolar tissues with drug-resistant periodontopathogens (respectively, interferon-a by 49.6%; interferon-y by 36.1% against the indicators - by 13.5% and 20.6% in patients with the drug-sensitive bacteria; p<0.05).

At the same time, it was found that higher products of the pro-inflammatory cytokines (IL-ip and TNF-a) and the reduction of the synthesis of anti-inflammatory cytokine IL-4 are more characteristic for patients with the rapidly progressing

parodontitis, carriers of the drug-resistant types of were found at colonization of the parodontium parodontal infection and less significant products tissues and drug-resistant bacterial agents.

Tab le 1

The characteristics of the immune status in patients with rapidly progressing generalized parodontitis depending on the sensibility of the marked strains of the periodontopathogenic bacteria (M±m)

Systemic immunity indicators Apparently healthy persons (n=24) Patients with the generalized periodontitis

sensitive to the common antibacterial therapy (n=42) resistant to the common antibacterial therapy (n=60)

CD 3 + (%) 54.9±1.1 51.8±1.4 47.8±0.6

CD4+(%) 39.8±0.9 38.2±1.2 34.7±0.5***

CD8+(%) 22.9±1.4 20.3±0.8 15.3±0.6*..

CD«+(%) 13.0±0.8 18.9±1.2* 16.1±0.4***

cd25 + (%) 18.4±0.4 12.1±0.4* 5.36±0.2*..

cd71+(%) 4.06±0.4 9.9±0.4* 15.4±0.7***

cd54+(%) 30.4±0.6 77.4±1.2* 98.2±0.6*..

CDU6+(%) 21.0±0.3 18.8±0.7 12.1±0.4***

CD,5+(%) 16.5±0.4 14.2±0.6* 7.0±0.2***

HLA- DR+ (%) 7.4±0.2 16.1±0.8* 14.2±0.3*..

SIgA (г/л) 1.48±0.2 0.65±0.03* 0.36±0.02***

IgA (g/1) 0.61±0.03 0.82±0.02" 0.74±0.02*..

IgG(g/l) 10.8±0.3 12.1±0.4* 13.2±0.3***

IgM (g/1) 0.51±0.02 1.08±0.61 0.22±0.01*..

a- INF (pg/ml) 13.4±0.9 20.6±0.4* 8.6±0.2***

у - INF (pg/ml) 27.8±1.9 22.7±1.6" 16.8±0.2*..

IL -ip(pg/ml) 70.9±3.4 199±6.2* 470.1±4.12***

TNF-a (pg/ml) 44.3±3.1 103.9±4.0* 207.8±6.0***

IL-4 (pg/ml) 82.8±6.4 49.6±5.l" 25.4±5.8*..

Notes: * p<0.05 is in regard to the standard values, ** p<0.05 is in regard to the group of drug-sensitive patients.

The expression levels of IL-ß and TNF-a in The difference of levels of the local products of

patients with the drug-resistant bacteria exceeded the IL-lß and FNO-a in the analyzed patients indicates

normal values by 6.5 and 4.7 times and in drug- undoubtedly to the more expressed activity of the

sensitive patients only by2.8 and 3.3 times. inflammatory-destructive process in parodontium in

patients with bacteria, which are resistant to the standard antibacterial agents, used in the integrated treatment of the disease. It is characteristic that the appearance in the periodontal ecological niche of the drug-resistant microorganisms and the intensification of the inflammatory process are accompanied by a sharp decrease of the products of antiinflammatory cytokine IL-4 (by 3.3 times respectively in comparison with the control values).

The suppression of synthesis of IL-4 was lower in patients whose periodontal tissues were colonized by drug-sensitive periodontopathogens (by 1.7 times).

The received data confirm the necessity to search for the available immunocorrection methods for any clinic, differential and effective in the clinical aspect, which can maximally eliminate the available immune system disorders in patients with the RPGP. depending on the drug- susceptibility of the periodontopathogenic flora, which colonizes the alveolartissues. to the protocol antibacterial agents.

As different immunomodulators affect pharmacologically the immune system in a different manner, and including the fact that in our study it was found that the disorders of immunological reactivity are as the determining factor of the course of inflammatory-destructive process in the alveolar tissues and can also influence the sensibility of the causative agents of the rapidly progressing generalized parodontitis to the traditional anti-infective drugs, it was showed a certain interest to the further study of the corrective action of polyoxidonium. li-copid and roncoleukin. prescribed for this pathology separately and in the form of combinations.

The first group includes 42 drug-sensitive patients and the II and the III groups (30 persons) include patients with the drug-resistant bacteria, which colonize the periodontal pockets. The polyoxidonium immunomodulator was prescribed to patients of the first and second group as an im-munocorrective therapy with the doses and course of administration, which are recommended in the instructions.

The integrated treatment protocol, along with immunocorrection. also included the similar traditional antibacterial therapy: chlorhexidine-con-taining drugs in combination with antibiotic Amo-xiclav in the III-rd group of patients; antibiotic lincomycin in representatives of the I and II groups according to the regulations, recommended by the manufacturers.

The estimation of the immediate results of the integrated treatment of the rapidly progressing parodontitis showed that the elimination of the inflammatory process was achieved in most of the studied persons from the first group (95.2% cases)

on the 6-7 day of treatment (in average on the 6.4±0.2 day) and only in 60% of patients of the second group (in average on 3.6±0.2 day), and in patients of the third group in 93.3% cases (in average on the 6.8±0.2 day of treatment) a delay was not. It should be noted, that, simultaneously with the elimination of the inflammatory process in the alveolartissues. the normalization of all gingival and dental plaque indexes was also marked. The paraclinical parameters in patients with the residual signs of inflammatory reactions in the gingival tissue had only atendency to some decrease.

As it turned out. the higher effectiveness of treatment in patients of the I and III groups than in patients of the II group was mainly due to a higher degree of correction of immunological disorders in patients of these groups (Table 2).

Polyoxidonium exerted a great positive influence on the immunopathological mechanisms only in patients with the rapidly progressing parodontitis in the conditions of the initial colonization of alveolar tissues with the drug-susceptible microorganisms (the first group of patients).

Against the background of the drug-resistant periodontopathogenic flora in the periodontal pockets, its use in the protocol of the integrated treatment turned out to be insufficiently effective regarding elimination of deficiency of the humoral and cellular component of immune system (the second group of patients). Despite the positive dynamics of the analyzed indicators, in general after its use the normalization of the most of the studied immunological parameters was detected in less than 50% of cases, and in the other cases there were signs of moderate insufficiency of the immunological resistance.

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It was found that the inclusion of the immunorehabilitation complex which includes polyoxidonium together with licopid or roncoleukin in the integrated therapy of patients with the rapidly progressing generalized periodontitis with drug-resistant periodontal pathogenic bacteria in the alveolar tissues, ensured elimination of disorders of the immune response in 93.3%.

In 3-6 months after the conducted treatment, the clinic-laboratorial results achieved in 90.3% of patients of the I and III groups were characterized with a stable stability. During this period of observation there were no cases of relapses of the infectious and inflammatory process, which was confirmed by the further dynamics of the gingival and periodontal indices. There was a decrease in the periodontal index by an average of more than 2 points and the depth of periodontal pockets was from 6.6±0.2 to 3.2 mm. The positive dynamics of parameters of cellular and local immunity was traced.

Tab le 2

Dynamics of humoral and cellular immunity parameters in patients with rapidly progressing generalized parodontitis who received different immunomodulating agents (M±m)

Groups of the studied persons

Parameters of immunity first group of patients, on medication with polyoxidonium (n=40) second group of patients, on medication with polyoxidonium (n=29) third group of patients, on medication with polyoxidonium together with licopid and roncoleukin (n=30)

before treatment after treatment before treatment after treatment before treatment after treatment

C D3+ (%) 51.6±1.2 55.2±l.l" 49.8±1.3* 50.8±1.2" 46.8±1.2* 52.9±0.8"

C D4+ (%) 38.8±1.2 40.3±0.8 35.8±1.2 34.7±1.2" 36.1±0.9 38.8±0.6"

C D8+ (%) 20.3±0.8 22.8±1.2 16.1±0.4" 17.1±0.9" 16.4±0.5" 30.1±0.9"

C D16+ (%) 18.2±1.2 13.2±0.7 14.0±0.6 13.4±0.6" 13.8±0.5 13.2±0.5

C D25+ (%) 12.4±0.4" 20.3±0.9" 15.5±0.7" 16.9±0.9" 15.2±0.6" 17.6±0.4"

CD71+(%) 9.9±0.4* 4.2±0.2" 2.9±0.3* 10.0±0.2" 6.1±0.4* 14.2±0.4"

C D54+ (%) 74.5±1.2" 32.5±1.4" 93.3±1.2" 60.2±l.l" 94.2±1.2" 27.1±0.6"

C D„6+ (%) 18.9±0.5 22.4±0.6" 12.6±0.4* 14.7±0.6" 12.8±0.4* 18.3±0.4"

C D,5+ (%) 14.0±0.5" 17.2±0.6" 7.3±0.4" 10.8±0.3" 7.7±0.4" 17.1±0.3"

HLA-DR+ (%) 16.4±0.6* 8.2±0.2" 18.8±0.5* 10.9±0.3" 19.1±0.6* 7.8±0.3"

slgA (g/1) 0.63±0.03* 1.45±0.03" 0.35±0.03* 0.67±0.04" 0.37±0.03* 1.29±0.3"

IgA(g/l) 0.85±0.02" 0.59±0.03" 0.73±0.05" 0.65±0.03" 0.75±0.05" 0.72±0.06"

IgG(g/l) 12.4±0.4* 12.0±0.4" 12.2±0.6* 12.0±0.3" 13.6±0.7* 11.1±0.4**

IgM(g/l) 1.07±0.04" 0.38±0.03" 0.23±0.02" 0.43±0.04" 0.21±0.02" 0.67±0.02"

a-INF (pg/ml) 10.8±1.8* 15.9±1.2" 8.5±1.3* 10.1±0.7" 8.7±0.3* 13.8±0.7"

y-INF(pg/ml) 22.6±1.4" 28.3±2.4" 17.0±1.15* 20.9±0.9" 16.6±1.03" 32.4±1.2"

Notes: *- the difference is significant (p<0.05) when compared with the group of healthy persons, compared with the indicators before and after treatment.

■ the difference is significant (p<0.05) when

CONCLUSIONS

1. The formation of different drug susceptibility of periodontopathogenic microorganisms to the protocol antibacterial therapy in patients with the rapidly progressing generalized parodontitis is closely related to the immunologic protocol diseases. The presence of drug-resistant bacteria in the periodontal tissues is combined with more expressed immune deficiency in the mechanisms of the system and local defense than in colonization of the affected areas with the drug sensitive periodontal microorganisms.

2. The features of immunity in patients with the rapidly progressing generalized parodontitis with the drug-resistant infection to the common antibacterial therapy is manifasted with the reduction of CD3 + lymphocytes, cells with cytostatic activity (C D4 +. CD16 +). expressing the receptors of lymphocytes activation (CD25 +. HLA-DR and apoptosis CD95+) against the background of some increase of CD20 +. CD116 +. CD54 +. with the significant depression of synthesis of slgA. IgM. a-INF. y-INF; expressed

МЕДИЧН1 ПЕРСПЕКТИВЕ / MEDICNIPERSPEKTIVI

with the increase of the products of the proinflammatory cytokines IL-ip h TNF-a.

3. A differentiated approach to the correction of immunological disorders in patients with the rapidly progressing generalized parodontitis depending on the detected sensitivity and resistance of perio-dontopathogenic bacteria to the protocol common antibacterial therapy, provides more fast arresting of

the infectious and inflammatory process (in average on 3.6±0.2 day), more than in 90%. it provides the normalization of the parameters of immunological reactivity in 93.3% of the observed persons and the stable clinical remission of the disease.

Conflict of interests. The authors declare no conflict of interest.

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Статгя надшшла до редакцп 16.09.2020

УДК 616.314.22-007.23-07-77:004.94 https://doi.Org/10.26641/2307-0404.2020.4.221411

О.О. Фастовець, РЕЗУЛЬТАТЫ ДОСЛ1ДЖЕННЯ

С. О. Сапалъов \ НАПРУЖЕНО-ДЕФОРМОВАНИХ CTAHIB

Я О. Штепа при ПРОТЕЗУВАНН1 Р13НИХ ТИП1В

АТРОФ11 НИЖНЬ01 БЕЗЗУБО? ЩЕЛЕПИ

ДЗ «Дн1пропетровська медична академ1яМОЗ Укра'ти»

кафедра ортопедичноё стоматологи

(зав. - д. мед. н., проф. О.О. Фастовець)

вул. В. Вернадського, 9, Днтро, 49044, Укра'та

Запор1зъкий державный медичний ynieepcumem

кафедра пропедевтичноё i xipypzi4H0i стоматологи

(зав. - к. мед. н., доц. С. О. Чертов)

пр. Маяковсъкого, 26, Запор1жжя, 69063, Укра'та

SE «Dnipropetrovsk medical academy of Health Ministry of Ukraine»

Department of Prosthetic Dentistry

V. Vernadsky str., 9, Dnipro, 49044, Ukraine

e-mail: ortho.stomat@dma.dp.ua

Zaporizhzhya State Medical University

Department of Propaedeutic and Surgical Dentistry

MayakovskyAve. 26, Zaporizhzhya, 69063, Ukraine

e-mail: p.stomat@zsmu.zp.ua

Цитування: Медичш перспективы. 2020. Т. 25, № 4. С. 146-158 Cited: Medicni perspektivi 2020;25(4):146-158

Ключов! слова: поена адент1я, нижня щелепа, зубне протезування, денталъна iмплантащя, ктцево-елементний анал1з

Ключевые слова: полная адентия, нижняя челюсть, зубное протезирование, дентальная имплантация, конечно-элементный анализ

Key words: complete adentia, mandible, complete dentures, dental implantation, finite element analysis

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