ORIGINAL ARTICLES. MEDICAL AND BIOLOGICAL SCIENCES
Background. Burn wound healing is recognized as a complex process involving synergetic interactions between different cells, cytokines and growth factors. The adverse interactions can underlie chronicization of the process. Accordingly, the paper presents a relevant study into mechanisms of natural wound dressings, capable of influencing the processes of inflammation, angiogenesis, and skin resurfacing.
Objective. To carry out a comparative evaluation of efficiency of burn wound healing with derma-based hydrogel according to the dynamics of proand anti-inflammatory factors.
Methods. Development of a hydrogel material involved dermis samples of Landrace breed of pig, subjected to partial alkaline hydrolysis. In order to carry out a comparative evaluation of burn wound healing efficiency, the authors simulated direct thermal injury in three groups of sphinx (hairless) rats: group 1 (control group) — rats without treatment (n = 20), group 2 (comparison group) — rats treated with Levomekol ointment (n = 20), and group 3 (experimental group) — rats treated with hydrogel material (n = 20). Before and after injuring on days 1, 3, 7, 14, the content of cytokines interleukin-1β, interleukin-4, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-α by enzyme immunoassay. The wound samples were explanted for histological examination on days 3, 7 and 14 after the beginning of the experiment. Statistical processing of the obtained results on DNA content in hydrogel, cytokine content in serum and morphometric data was performed using GraphPadPrism 6.04, Microsoft Excel 2016 (Microsoft, USA).
Results. When determining the content dynamics of nonspecific markers of inflammation, an increase in the concentrations of interleukin-1β and tumor necrosis factor-α on day 1 after the hydrogel application was recorded, as well as an increase in interleukin-6 on days 3 and 7, while the concentrations of interleukin-8 did not change significantly throughout the experiment. Thus, dermal components are indicated to participate in the inhibition of acute-phase immune reactions. With regard to anti-inflammatory factors, the study revealed a decrease in the concentration of interleukin-10 on days 1 and 7, an increase in interleukin-4 on day 3 as compared to the control group, thereby indicating a pronounced anti-inflammatory effect and prolonged action of the hydrogel.
Conclusion. Comparative analysis of the pro-inflammatory cytokines levels (interleukin-1β, interleukin-8) showed pronounced anti-inflammatory effects of the derma-based hydrogel material. Introduction of exogenous biological components of the extracellular matrix (collagen and its hydrolysates) had a significant influence on the regulation of anti-inflammatory cytokines synthesis, presumably contributing to faster successful epithelization and wound healing.
Background: The multifaceted regulatory role of nitric oxide in biological systems predetermines the high value of studying the possibilities of the external control of the compound level in organs and tissues. There are several fundamentally different ways of exogenous modulation of nitric oxide metabolism. The most promising option is the use of pharmacological donors. Dinitrosyl iron complexes (DNIC) with various ligands hold a prominent place among such donors as they are considered as a natural deposited form of nitric oxide.
Objective. To study the effect of a glutathione-containing dinitrosyl iron complex on the oxidative metabolism parameters and crystallogenic activity of rat blood.
Methods. A preclinical experimental randomized study was conducted on 60 sexually mature male Wistar rats weighing about 250 g. The animals were divided into 6 groups, each consisting of 10 individuals. Group 1 included intact (without any manipulations) individuals. In group 2, the rats were administered daily intraperitoneal injections of 1 ml. of 0.9% sodium chloride solution for 10 days. The rats included in the other four groups received daily intraperitoneal injections of 1 ml of dinitrosyl iron complexes with glutathione ligands in an isotonic sodium chloride solution with different agent concentrations: 0.15 mM for group 3; 0.30 mM for group 4; 0.45 mM for group 5; 0.60 mM for group 6. The final indicator of the study was the assessment of the oxidative potential and crystallogenic properties of blood under the conditions of administering various doses of glutathione-containing dinitrosyl iron complexes. The following parameters were used to assess the activity of proand antioxidant systems: lipid peroxidation intensity; the total activity of antioxidant systems, and malondialdehyde concentration. The parameters for intrinsic crystallization assessment included serum facies structural index, crystallizability, assessment of the marginal facies zone, and the destruction degree of facies elements. The obtained data calculation was performed using the software packages MS Office 2013 (Microsoft Corporation, USA) and Statistica 10 (StatSoft, USA).
Results. The research established that glutathione-containing dinitrosyl iron complexes have an antioxidant effect. Moreover, the manifestation of these properties demonstrates a nonlinear dependence on their dose, with a possible optimum lying in the range of 0.3–0.45 mM. The study also revealed a tendency towards crystallogenic properties activation induced by this agent, corresponding to concentrations of 0.3 and 0.45 mM.
Conclusion. The undertaken studies indicate the presence of an antioxidant effect in glutathione-containing dinitrosyl iron complexes. The manifestation of these properties demonstrates a dependence on their dose with a possible optimum varying from 0.3 to 0.45 mM. The research has established the activating effect of glutathione-containing dinitrosyl iron complex injections on the crystallogenic potential of the blood serum of healthy rats. This effect consisted in an increase in the density and complexity of crystalline elements. What is more, the maximal manifestation of this tendency (for metabolic indicators as well) corresponded to concentrations of 0.3 and 0.45 mM.
Background. Injuries of various origins with damage to parenchymal organs remain one of the urgent issues of emergency surgery, despite all the achievements of medical science of the first quarter of the XXI century. One way to improve the quality of treatment for patients with this pathology consists in developing new wound dressings or modifying the properties of existing ones. Hemostatic efficacy is claimed to be one of the main requirements for such dressings.
Objective. To perform a comparative analysis of the efficacy of the developed biodegradable wound dressings based on chitosan in the treatment of experimental wounds of parenchymal organs.
Methods. The study involved laboratory animals (male rabbits weighing 2900 ± 150 g) to form experimental wounds of parenchymatous organs. The methodology involved wounding the liver via internal method, with the creation of a tissue defect of a given volume, or forming a linear incised wound with fixed parameters followed by application of a developed wound dressing. In the control group of animals, a collagen hemostatic sponge was used as a wound dressing. The animals used in the experiment were kept in accordance with GOST 33044-2014 “Principles of good laboratory practice”. The experiment involved studying the properties of two samples of wound dressings developed on the basis of modified Chitosan Soft (Ch-S) and Chitosan Hard (Ch-H) chitosan, having different properties due to their different structural parameters. The applied ultrasound control of the experimental wound area, with visualization of the samples of the investigated material in the process of biodegradation, enabled the features of the wound process to be studied in more detail. Statistical processing of the study results was carried out by methods of variational statistics, including the calculation of mean values (M), standard errors of mean values (± m). The criterion of the level of statistical significance considered a value of p <0.05. Histomorphological examination of samples was carried out using classical methods.
Results. An experimental study conducted on laboratory animals in the treatment of liver wounds, followed by a comprehensive assessment of the results obtained, revealed high efficacy in the developed wound dressings in comparison with the control. The following parameters predicted in the development of wound dressing samples were confirmed: stable hemostatic and scaffold functions, biodegradability, adhesiveness and stimulating effect on bioreparative processes in the wound area. In addition, the ultrasound control algorithm in vivo was adapted in animals to assess the dynamics of the wound process and biodegradation of the studied wound dressings in wounds of parenchymal organs in the experiment, previously used in studying the dynamics of the wound process in soft tissues.
Conclusion. The developed samples of chitosan-based wound dressings proved their efficacy in an experimental model of the wound process in parenchymal organs. The applied ultrasonic method for monitoring the biodegradation of the studied wound dressing, as well as the dynamics of the wound process in the liver tissue, revealed the correspondence between the visualized image and the histomorphological picture of the studied tissues, the structure and properties of the wound dressing.
ORIGINAL ARTICLES. CLINICAL MEDICINE
Background. Prostate cancer maintains a relatively high standardized uptake value and share of patients followed up for 5 or more years. Accordingly, distant outcomes in these patients appear to be influenced by factors other than the underlying disease.
Objective. To analyze the morbidity in prostate cancer patients with additional malignancies potentially linked with the decrease in the survival rate in the Mari El Republic.
Methods. The present study involved 1434 prostate cancer patients firstly enrolled in the period from 2012 to 2021. A group of patients in this sample was identified with additional malignancies (other than prostate cancer) diagnosed within the period from 6 months prior to prostate cancer diagnosis to the end of 2021. Comparison of the incidence of malignancies among prostate cancer patients and the general population was performed via a 2 × 2 crosstab analysis by calculating the relative risk and its 95% confidence interval. The difference was considered significant when 95% confidence interval did not include 1. In addition, chi-square values and corresponding p-values were calculated. Statistical analyses were performed using SPSS 13.0 (SPSS Inc., USA) and Microsoft Excel 2007 (Microsoft Corporation, USA).
Results. 31 (32.29%) additional malignancies were identified (prostate cancer was diagnosed within 6 months before prostate cancer diagnosis and up to 6 months thereafter), 7 additional malignancies (7.29%) were registered 6 months to 1 year after prostate cancer diagnosis, and 61 additional malignancies (63.54%) during the later period. The most common primary malignancies among all patients included: bladder cancer (relative risk = 15.23 [95% confidence interval: 10.42–22.26]), nonmelanoma skin cancer (relative risk = 3.77 [2.34–6.07]), colorectal cancer (relative risk = 2.10 [1.24–3.54]), gastric cancer (relative risk = 2.01 [1.08–3.73]), and kidney cancer (relative risk = 4.69 [2.51–8.75]).
Conclusion. Within 7.1 years (median) of follow-up, additional malignancies develop in 6.70% of prostate cancer patients. These patients reveal the higher risk than the population average value, thereby constituting a risk group.
REVIEW
Background. The Constitution of the Russian Federation and federal laws define the main postulates of the methodology for preventive measures as a priority in the field of public health. Sectoral regulatory legal acts, namely, orders of the Ministry of Health of Russia present the methodology as a system of principles and methods for organizing preventive activities, including health check-ups of the adult population. The effectiveness of the largest preventive measure of the Russian health care system — health check-ups of certain groups of the adult population — depends on the quality and validity of the methodological provisions of the regulatory legal act.
Objective. To assess the completeness and objectivity of methodological approaches to conducting and evaluating medical check-ups of certain groups of the adult population, reflected in regulatory legal acts.
Methods. The research methodology involved a systematic review of the regulatory documentation of the Russian Federation in the field of health care from January 2012 to December 2022 to verify the basics of the methodology for conducting and evaluating preventive measures for certain groups of the adult population. The information was searched in the database of the ConsultantPlus legal reference system and on the official website of the Ministry of Health (Russian Federation), as well as in the electronic databases of the CyberLeninka and eLIBRARY.RU scientific electronic libraries. The study involved the methods of content analysis, analytical generalization, analogies, and formalization. Data analysis was focused on the organization of the health check-up of the adult population, the evaluation of its performance and effectiveness in accordance with regulatory legal acts, as well as the assessment of the quality of data obtained during the check-up.
Results. A dynamic retrospective study of the regulatory framework, including the orders of the Ministry of Health of Russia, both those that have expired and those that are currently in force, identified methodological shortcomings in conducting and evaluating medical check-ups. The methodology for health check-ups of the adult population is reflected in regulatory acts. However, their number exceeds one or several documents, thereby creating a certain complexity in their interpretation and use in practice. The methodology for assessing and monitoring the implementation of health check-ups appears to be poorly defined, since it is based on a single indicator — coverage of the population with preventive check-ups and clinical examinations, thereby failing to reflect the real effect of the largest preventive measure of the state health care system. The issue requires new methodological approaches to conducting and evaluating health check-ups as a whole. The study and evaluation of check-up results is based on the statistical data analysis with imperfect methodology for collecting the data. This negatively affects the quality of statistical data, thereby leading to inadequate interpretation of the data and, as a result, to erroneous management decisions made at all levels of the executive branch.
Conclusion. It is advisable to develop general methodology for conducting medical check-ups, and to consider the feasibility of creating an integral indicator for evaluating them. Specialists in the field of health care, as well as in related fields, should be involved for this purpose. A medical health officer should be assigned to coordinate the development of a methodology for organizing, conducting and evaluating health check-ups.
CLINICAL CASE
Introduction. Gottron’s papillomatosis is a rare benign type of dermatosis with pseudoepitheliomatous hyperplasia of the epidermis, first described as an independent disease by the German dermatologist H.A. Gottron. Invasive epidermal growth and hyperkeratosis reveal no signs of malignancy. Chronic venous insufficiency and lymphedema can be associated with various secondary skin lesions: the formation of ulcers, hyperkeratosis and skin papillomatosis, as well as infectious complications. Skin papillomatosis may be a manifestation of paraneoplastic syndrome, which requires a careful differential diagnosis. Timely treatment of complications in a patient with concomitant somatic pathology performed by a multidisciplinary team of specialists is necessary to improve the prognosis. Considering the relative rarity of Gottron’s papillomatosis and the lack of awareness among practicing physicians regarding the differential diagnosis of this disease, we present this clinical analysis.
Description of a clinical case. Patient L., 42 years old (body mass index — 76.5 kg/m2) with chronic lymphovenous insufficiency, lymphedema, erysipelas of the right lower limb associated with unspecified skin papillomatosis, was urgently hospitalized in a health care institution “City Clinical Hospital No. 3” of Grodno (Republic of Belarus), consulted by a multidisciplinary team of clinicians including a therapist, a cardiologist, a dermatologist, an endocrinologist, an infectious disease specialist, and a surgeon. Taking into account the clinical status of the patient and the retrospective analysis of archival records of previous examinations performed on the patient in the health care institution “Grodno University Clinic”, the type of dermatosis was determined as Gottron’s papillomatosis of both lower extremities. In terms of the clinical diagnosis of the patient, complex therapy was initiated in a hospital setting, which was then continued at the outpatient stage.
Conclusion. Adequate long-term treatment of morbid obesity and chronic lymphovenous insufficiency is necessary to prevent serious complications. According to the academic literature, timely diagnosis of such a rare dermatosis as Gottron’s papillomatosis, as well as the prescription of adequate therapy determine the possibility of regression in the early stages of the disease.
Introduction. A differential diagnostic search is a crucial method for making a final clinical diagnosis. Lack of clinical thinking leads to tactical errors, both in making a diagnosis and in choosing a therapy algorithm. The problem of iatrogeneses especially often arises at the initial stages of patient management.
Case descriptions. The paper demonstrates the difficulties of verifying the diagnosis of patients with dermatological pathology on the example of clinical cases. The stages of differential diagnostic search are covered in detail. Practicing physicians stress the importance of timely correct diagnosis and, consequently, the choice of therapy. The study involved a detailed analysis of clinical cases and mistakes causing a delay in diagnosis and wrong choice of therapeutic tactics at the outpatient stage. A clinical case with designated diagnosis is presented and analyzed as an illustrative example. Special attention was given to a complex evaluation of subjective, objective and diagnostic data, the significance of analyzing the development of dermatoses.
Conclusion. Careful adherence to diagnostic algorithms will avoid iatrogenic errors and thereby improve the quality of medical care and the quality of life of dermatological patients.
BRIEF COMMUNICATIONS
Background. Lichenoid reactions of the oral mucosa are currently recognized as a serious issue for dentists of various specialties, since their knowledge and competence in the diagnosis and pathogenetic treatment of lichenoid lesions of the oral cavity are yet to be improved. Following the data on high oncogenic potential in some forms of lichenoid reactions of oral cavity mucous membranes, the issue should be given serious considerations, and dentists should keep oncology-related suspicion when receiving these patients.
Objective. To evaluate the efficacy of comprehensive dental treatment for lichenoid reactions of the mucoparodontal complex.
Methods. A single-center pilot cohort study was conducted to evaluate the efficacy of the comprehensive treatment (combination of pharmacotherapy and physiotherapy) of patients with lichenoid reactions of the oral mucosa. The observation group consisted of 49 patients (15 males, 34 females) aged 58.92 ± 0.82 years with verified diagnoses of oral mucosa lichenoid reactions. The suggested treatment included pharmacotherapy (highly-potent topical steroids, calcineurin inhibitors) and physiotherapy in the form of low level laser therapy (635 nm, 10 W) provided via Matrix laser (Matrix, Russia). Treatment efficacy was assessed by the total scale of treatment efficacy, registering indicators of the area of focal lesions and the severity of pain syndrome, as well as by changes in dental quality of life indicators according to OHIP-49-RU (Oral Health Impact Profile) in the Russian version. Statistical processing of the data involved Student’s t-test and Wilcoxon t-test. Differences were considered significant at p ≤ 0.05. Data statistical analysis was performed using SPSS 13.0 (SPSS Inc., USA).
Results. During the follow-up period, the indicators of the total scale of treatment efficacy decreased significantly (p < 0.001) in 100% of patients and amounted (as medians and quartiles): 6.0 (4.0–7.0) points before treatment and 1.0 (1.0–2.0) points after treatment to be objectified by a significant reduction in the area of focal lesions (by 63.2%, p < 0.001) and in pain syndrome (spontaneous pain from 2.0 (1.5–3.0) points before treatment to 0.0 (0.0–1.0) points after treatment; induced pain from 3.0 (2.0–3.0) points to 1.0 (0.0–1.0) points). Along with the clinical improvement, the scores in dental quality of life improved from 83.11 ± 2.58 to 39.94 ± 0.86 points, according to OHIP-49 RU (Oral Health Impact Profile).
Conclusion. Early detection and differentiation of lichenoid reactions in oral mucous membranes ensure timely treatment using the developed protocol of comprehensive treatment (combination of pharmacotherapy and physiotherapy). The efficacy of the protocol was confirmed clinically and justified in relation to quality of life.
ISSN 2541-9544 (Online)