Vol 28, No 3 (2020)

Оригинальные исследования
Peculiarities of influence of NO-synthase inhibitors on behavioral parameters of rats
Bashkatova V.G., Bogdanova N.G., Alexeeva E.V., Nazarova G.A., Sudakov S.K.

Aim. A comparative study of the influence of nitric oxide synthase (NO-synthase) inhibitors on the parameters of anxiety, motor activity and pain sensitivity of rats.

Materials and Methods. The work was conducted on male rats of Wistar line. The anxiety level and locomotor activity of rats were studied in the «elevated plus maze» (EPM) test. Pain sensitivity of the animals was tested on the «hotplate» apparatus. In the work, selective inhibitor of inducible isoform of NO-synthase – aminoguanidine – at a dose of 50 mg/kg, and non-selective inhibitor of this enzyme – N-nitro-L-arginine – at a dose of 50 mg/kg, were used. Rats of the control group were introduced the equivalent quantity of normal saline.

NO-synthase inducible inhibitor – aminoguadinine did not produce any influence on the anxiety level, but led to reduction of the horizontal motor activity of rats. Introduction of non-selective NO-synthase inhibitor – N-nitro-L-arginine – was accompanied by reduction of the anxiety and of the locomotor activity of animals in the EPM test. Both investigated NO-synthase inhibitors induced alteration of pain sensitivity of rats in the form of hypoalgesia. Here, the most pronounced nociceptive effect was observed with introduction of non-selective NO-synthase inhibitor.

Conclusion. In the work the evidence of participation of inducible isoform of NO-synthase in realization of the motor activity and pain sensitivity processes in rats is shown. In result of the conducted experiments it was found that introduction of non-selective NO-synthase inhibitor N-nitro-L-arginine was accompanied by evident alterations of anxious behavior, locomotor activity and nociceptive sensitivity of rats. The results obtained confirm the important role of the system of regulation of nitric oxide synthesis in neurochemical mechanisms of behavioral reactions in rats.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):275-282
Factors of biological nature in work of mobile teams of emergency medical care station on the eve of pandemics of new coronavirus infection (COVID-19)
Bolobonkina T.A., Dementyev A.A., Shatrova N.V., Yankina S.V.

Aim. Determination of the actual spectrum of pathogenic microorganisms to which medical workers of mobile teams of emergency medical care (EMC) are exposed, and scientific justification of the class of the working conditions of this professional group in terms of the biological factor.

Materials and Methods. Data of the electronic journal of the automated «Ambulance Service» control system for infectious patients, and records of the register for infectious diseases among workers of the municipal emergency medical care station of Ryazan (300 medical assistants, 64 doctors) for 2016-2019 were used.

Results. The average amount of calls to patients with infectious pathology in 2016-2019 made 2178.5±221.3 per year. Most emergency calls were for intestinal infections, common cases were varicella, erysipelas, viral hepatites, tuberculosis infection, herpes zoster. The main load in servicing these calls fell on linear (from 63.7 to 77.4%) and pediatric (from 24.8 to 35.1%) teams; calls of resuscitation teams to patients of such profile were sporadic. The level of infectious morbidity of doctors made 0.78 cases per 100 doctors which is 1.2-fold higher than the level of medical assistants (t=3.79; р=0.0003).

Conclusion. The confirmed cases of diseases of the studied group of workers resulting from professional contacts with sources of infections of Group III pathogenicity permits to refer the working conditions of medical workers of mobile teams of emergency medical care stations to hazard Class II. However, a high probability for professional contact with high pathogenicity strains of group A influenza, HIV-1 and HIV-2, hepatitis C, D, E viruses belonging to Group II pathogenicity, and existence of the evident contacts with SARS-CoV-2, permit to raise the class of the working conditions to hazard Class III.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):283-289
Prognostic role of results of dynamic capnography in integral assessment of parameters of respiratory system in 6-minute walk test in patients with chronic heart failure
Ageeva K.A., Filippov E.V.

Aim. To study the prognostic value of the results of dynamic capnography in the complex assessment of parameters of the respiratory system in 6-minute walk test in patients with chronic heart failure (CHF).

Materials and Methods. 73 Patients were examined: the group of study included 48 patients with IIA or IIB stage CHF (mean age 57.9±4.6 years, 23 men), the control group included 25 practically healthy volunteers (mean age 47.6±3.5 years, 9 men). The patients were conducted complex determination of parameters of the respiratory system: clinical scaling before and after 6-minute walk test (6MWT), instrumental examinations including spirometry, capnography and pulse oximetry before, during and after physical activity. The analysis of survival was conducted on the basis of the dynamic follow-up of patients within 5 years (60 months).

Results. In the analysis of parameters of dyspnea at rest, all the parameters were higher in the group of patients with CHF (р<0.05). The distance walked by the patients with CHF in 6 minutes was 488.23±90.84 m, which was significantly less than in the control group (815.60±53.89 m, р=0.009). Dyspnea as the cause of stoppage/slowing down of walking in 6MWT, was also more often recorded in patients with CHF (93.8±3.0% and 48.0±5.1%, р=0.049). Besides, in 6MWT the patients noted: weakness in legs (50.1±5.0% in the group of CHF and 40.0±5.0% in the control group, р=0.014), palpitation (29.0±4.6% and 20.0±4.1%, respectively, р=0.004). Worsening of dyspnea parameters in 6MWT was more evident in patients with CHF than in the control group (р<0.01). In the CHF group, hypocapnic type of ventilation was revealed in 6MWT, analysis of РЕТСО2 trend graphs revealed a wave-like increase in the parameters, the so called periodic breathing (PB). CO2 trend was recorded in CHF group in 58.3±1.0% of cases (the difference with the control group with р=0.046), the trend of heart rate – in 18.8±0.3% of cases (р=0.027). Cox proportional hazards regression analysis of mortality in patients with CHF showed a prognostic significance of a complex model comprising the following parameters of a patient: body mass index (р=0.005), left ventricular end-diastolic dimension (р=0.034), left ventricular end-systolic dimension (р=0.002), left ventricular ejection fraction (р=0.041), 6MWT distance (р=0.004), desaturation (р=0.009), and the presence of signs of PB during 6MWT (р=0.005). Model coefficients were statistically significant at р<0.0001.

Conclusions. Dynamic capnography and pulse oximetry allow to identify signs of PB in patients with CHF during 6MWT which may deepen a complex assessment of parameters of the cardio-respiratory system in patients with CHF in order to determine tolerance to physical exercise as well as the effectiveness of the conducted treatment. Complex assessment of survival of patients with CHF showed prognostic significance of the following parameters of a patient: body mass index, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, left ventricular ejection fraction, 6MWT distance, desaturation, PB during 6MWT.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):290-299
Characteristics of clinical and anamnestic data and of condition of primary hemostasis in chronic diseases of liver in children
Konovalova E.Y., Lavrova A.E., Presnyakova M.V.

Aim. To perform a comparative analysis of clinical and anamnestic data and of the condition of primary hemostasis in chronic liver diseases in children and to identify additional informative diagnostic criteria that reflect severity of the course of autoimmune hepatitis (AIH) and chronic viral hepatitis C (CVHC) in children.

Materials and Methods. 91 Patients from 3 to 7 years old were examined, of them: 60 children with AIH and 31 children with CVHC. The control group included 15 children of I and II health groups. In all the patients the clinic-anamnestic data and the condition of the primary hemostasis were evaluated. Concentrations of endothelin-1 and homocysteine, activity of Willebrand factor, amount of platelets and their aggregation activity were determined.

Results. AIH is characterized by a more aggressive course as compared to CVHC manifested by clinical signs of a severe liver damage, significant biochemical changes and a high rate of fibrosis within the first two years. In all the children there were found disorders in the primary hemostasis interrelated with the main clinical and laboratory syndromes reflecting the severity of the liver damage. AIH is characterized by a higher concentration of homocysteine (р=0.007) and of the activity of Willebrand factor (р=0.037) in comparison with CVHC.

Conclusions. Signs of a severe liver damage are not characteristic of children with CVHC in the first 10 years of the disease, however, disorders of the primary hemostasis are present characterized by hyperaggregation of platelets and by endothelial dysfunction. AIH in children is characterized by aggressive course and more pronounced deviations of the primary hemostasis in comparison with CVHC. In AIH and CVHC, the pathology of the primary hemostasis is closely related to some clinical-laboratory symptoms that reflect severity of the disease.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):300-311
Immediate and long-term results of carotid endarterectomy in different periods of ischemic stroke
Kazantsev A.N., Chernykh K.P., Zarkua N.E., Lider R.Y., Burkova E.A., Bagdavadze G.S., Kalinin E.Y., Zaitseva T.E., Chikin A.E., Linets Y.P., Kubachev K.G.

Aim. Analysis of hospital and long-term results of carotid endarterectomy (CEA) in different periods of acute cerebrovascular event (ACVE).

Materials and Methods. The given study was retrospective and was conducted using the method of patients sampling. In the period from 2010 to 2019, 1113 patients with ACVE in history who were later conducted CEA, were selected. Depending on the time interval between the last ACVE and CAE, all the patients were divided into 4 groups: the 1st group – in the acutest period of ACVE (1-3 days) (n=24; 2.2%); the 2nd group – in the acute period of ACVE (up to 28 days) (n=493; 44.3%); the 3rd group – in the early rehabilitation period of ACVE (up to 6 months) (n=481; 43.2%); the 4th group – in the late rehabilitation period of ACVE (up to 2 years) (n=115; 10.3%). The long-term period was 34.8±12.5 months.

Results. In the hospitalization period of observation the following complications were found: lethal outcome ((group 1 – 0%; group 2 – 0.4% (n=2); group 3 – 0.2% (n=1); group 4 – 0%; р=0.16)); myocardial infarction ((group 1 – 0%; group 2 – 0.4% (n=2); group 3 – 0%; group 4 – 0.9% (n=1); р=0.35)); ACVE/transient ischemic attack (TIA), ((group 1 – 4.2% (n=1); group 2 – 0.4% (n=2); group 3 – 0.2% (n=1); group 4 – 0%; р1-2=0.01; р1-3=0.009; р1-4=0.01)). By the end of hospitalization period the composite endpoint consisting of lethal outcome + myocardial infarction + ACVE/TIA made in group 1 – 4.2% (n=1), in group 2 – 1.2% (n=6), in group 3 – 0.4% (n=2), in group 4 – 2.6% (n=3), р=0.08. Complications of the long-term follow-up period were: lethal outcome from all causes ((group 1 – 25% (n=6); group 2 – 5.5% (n=27); group 3 – 7.3% (n=35); group 4 – 14% (n=16); р1-2=0.002; р1-3=0.008; р2-4=0.012)); lethal outcome from cardiovascular causes ((group 1 – 4.2% (n=1); group 2 – 3.6% (n=18); group 3 – 4.8% (n=23); group 4 – 5.2% (n=6); р=0.79)), myocardial infarction ((group 1 – 12.5% (n=3); group 2 – 3.6% (n=18); group 3 – 5.4% (n=26); group 4 – 6.1% (n=7); р=0.15)), ACVE/TIA ((group 1 – 16.6% (n=4); group 2 – 6.3% (n=31); group 3 – 6% (n=29); group 4 – 11.3% (n=13); р=0.05)); composite endpoint including lethal outcome + myocardial infarction + ACVE/TIA ((group 1 – 54.2% (n=13); group 2 – 15.4% (n=76); group 3 – 18.7% (n=90); group 4 – 31.3% (n=36); р1-2=0.0001; р1-3=0.0001; р1-4=0.005; р2-4=0.0006; р3-4=0.012)).

Conclusion. Application of CEA demonstrated effectiveness and safety in the acute and early rehabilitation period of ACVE.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):312-322
Determination of clinical efficiency of deproteinized dialysate from blood of milk-fed calves after endoprosthetics in patients with ventral hernias
Ivanov S.V., Ivanov I.S., Obyedkov E.G., Popova L.P.

Aim. To study the influence of deproteinized dialysate from blood of milk-fed calves on the type of exudative discharge and dynamics of inflammatory reaction after hernia repair with plastics of the anterior abdominal wall with hernioendoprosthesis of polypropylene.

Materials and Methods. The study involved 59 patients being on stationary treatment in the surgical department of Kursk Regional Clinical Hospital. Patients were hospitalized for the herniation of small or medium dimension. The patients were divided to two groups: the main (n=30) and control (n=29) groups. After endoprosthetics, the patients of the control group were given complex conservative treatment. The patients of the main group, besides standard treatment, were administered deproteinized dialysate from blood of milk-fed calves intravenously in drips 10 ml + 200 ml of 0.9% sodium chloride solution within 7 days. For cytological examination and determination of the type of cytograms, the traumatic discharge was collected and analyzed using the method of M.F. Kamaev and M.A. Palthsev.

Results. Cytomorphometric examination was conducted on the third, fifth and seventh day after endoprosthetics with the aim of studying dynamic changes. Determination of cell composition and also of its changes characteristic of each studied period, was necessary for obtaining further information characterizing inflammatory process in the region of placement of the endoprosthesis. After endoprosthetics in patients who were administered hemodialysate, the inflammatory reaction was less pronounced than in patients who did not receive the preparation. This was associated with a more dynamic change of stages of the inflammatory process. In patients of the main group who received deproteinized dialysate, regenerative type of inflammation first appeared on the fifth day and made 6.9%; by the seventh day the share of patients with the regenerative type rose to 17.5%, while in the patients of the control group no regeneration stage was observed in both periods.

Conclusion. Analysis of the efficiency of influence of hemodialysate on the inflammatory reaction in plastics of the anterior abdominal wall with polypropylene endoprosthesis evidences faster course of all stages of inflammation and reduction of its intensity by 10%.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):323-333
Diagnostic value of laparoscopic inguinal allohernioplasty in detection of occult hernias of inguinal region
Zaitsev O.V., Koshkina A.V., Khubezov D.A., Yudin V.A., Barsukov V.V.

Aim. To evaluate diagnostic value of laparoscopic inguinal allohernioplasty in identification of occult forms of hernias of the inguinal region.

Materials and Methods. The study was conducted on the basis of the results of surgical treatment of patients with inguinal hernias on the base of the Department of Hospital Surgery of RyazSMU in Ryazan State Emergency Care Hospital and on the base of the Department of Surgery, Obstetrics and Gynecology of Additional Postgraduate Education Faculty in Ryazan Regional Clinical Hospital, from 2015 to 2020 (n=207). Operations were performed with the absence of contraindications to narcosis and carboxyperitoneum, and if patients desired to be operated on by the proposed method. In all the patients included into the study, hernioplasty was performed using laparoscopic approach, with preperitoneal placement of the endoprosthetic mesh. For purity of the experiment, only polypropylene meshes were used. Standard meshes from monofilament polypropylene were used with surface density 65-80 g/m2 and volumetric porosity 80-85%. Meshes 15x15 cm dimension were used with cut angle with 7.5A cm catheti.

Results. Of 207 patients, 28 were operated on for bilateral inguinal hernias. Only in one of them hernia was diagnosed in the preoperative stage. In the rest 27 patients, an occult hernia was found opposite to the previously diagnosed side. In 17 patients, besides hernias diagnosed in the preoperative and intraoperative stages, occult hernias were detected in the process of dissection of the preperitoneal space.

Conclusion. Laparoscopic inguinal allohernioplasty permits to diagnose occult hernias that were not detected in the preoperative examination: femoral, obturator, inguinal hernias on the contralateral and/or unilateral side. This permits to perform hernioplasty taking into account the intraoperative finding, in one surgical procedure without subjecting the patient to repeated hospitalization, narcosis and operation.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):334-339
Venous resections and reconstructions in surgery of pancreatic cancer
Kit O.I., Katelnitskaya O.V., Maslov A.A., Gevorkyan Y.A., Kolesnikov E.N.

Aim. To evaluate results of venous resections in tumor infiltration of venous wall in pancreatic cancer (PC).

Materials and Methods. The study included 74 patients with PC and tumor invasion of the wall of the mesenteric-portal system (T3 N0-1 M0). The control group included patients (n=53), receiving palliative chemotherapy. The average age of patients in the group of surgical treatment was 61.8±9.8 years, in the control group – 63.2±10.1 years (р>0.05), the average diameter of the tumor was 39 mm and 43 mm, respectively (р>0.05). In 62 cases of the group of surgical treatment the tumor was located in the head of pancreas (P), the patients were conducted pancreaticoduodenal resection with venous resection. In the rest of cases (n=12) the tumor was located in the body of P, corporocaudal resection of P was conducted with venous resection.

Results. In the early postoperative period 2.7% of patients developed thrombosis of the reconstruction zone, 1.4% developed bleeding. 30-Day postoperative lethality was 4.1%. Median survival in surgical treatment of PC with venous resection was higher in comparison with palliative chemotherapy: 19 months vs 13 months, р<0.05. In the group of venous resection the lowest annual survival (46.2%) was noted in patients with marginal resection of the vein. No significant differences were found in the parameters of survival with use of direct venous anastomose and venous prosthetics (66.7% vs 63.2%, p>0.05).

Conclusions. Angioplastic interventions permitting to achieve microscopically complete resection of the tumor in PC with tumor infiltration of mesenteric-portal system, permit to improve survival of patients in comparison with palliative chemotherapy.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):340-349
Клинические случаи
Combination of the right heart pathology and varicose disease as a factor of development of trophic changes in the lower extremities: a case report
Kalinin R.E., Suchkov I.A., Patel M.D., Shanaev I.N., Mzhavanadze N.D.

Varicose disease is the most prevalent vascular disorder affecting lower extremities. Chronic venous insufficiency (CVI) is common in subjects with incompetent superficial and perforator veins. Major attention in pathogenesis of CVI is paid to horizontal venous reflux, while pathological blood flow in the superficial veins may sometimes be regarded as a postural reaction. At the same time cardiac pathology may also attribute to the development of CVI. The article presents a case report describing a female patient with combination of the right heart pathology and varicose disease associated with tricuspid regurgitation leading to constant venous reflux in the lower extremity superficial veins with further development of trophic changes.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):350-359
Participation of ABCA1 transporter in development of chronic obstructive pulmonary disease
Kotlyarov S.N., Kotlyarova A.A.

Despite all achievements of the modern medicine, the problem of chronic obstructive pulmonary disease (COPD) does not lose its relevance. The current paradigm suggests a key role of macrophages in inflammation in COPD. Macrophages are known to be heterogeneous in their functions. This heterogeneity is determined by their immunometabolic profile and also by peculiarities of lipid homeostasis of cells.

Aim. To analyze the role of the ABCA1 transporter, a member of the ABC A subfamily, in the pathogenesis of COPD. The expression of ABCA1 in lung tissues is on the second place after the liver, which shows the important role of the carrier and of lipid homeostasis in the function of lungs. Analysis of the literature shows that participation of the transporter in inflammation consists in regulation of the content of cholesterol in the «lipid rafts» of the membranes, in phagocytosis and apoptosis.

Conclusion. Through regulation of the process of reverse transport of cholesterol in macrophages of lungs, ABCA1 can change their inflammatory response, which makes a significant contribution to the pathogenesis of COPD.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):360-370
Non-invasive diagnostics of endometriosis: review of modern biomarkers of peripheral blood and endometrium
Kiselev M.A., Repina N.B.

Endometriosis is a chronic progressing estrogen-dependent disease with a high incidence among females characterized by pelvic pain (40-80%) and infertility (25-80%).

Aim. To analyze and estimate the modern literature data on the possibility of using potential biomarkers of endometriosis in its non-invasive diagnostics.

In recent years, researchers have made significant advances in understanding the disease-specific molecular pathways that regulate the development of ectopic foci of endometriosis, by examining the blood, peritoneal fluid, and eutopic endometrium in women with the disease. Along with understanding the pathophysiology of endometriosis, the question of finding an adequate biomarker that will provide an effective early non-invasive diagnosis of endometriosis and, accordingly, preserve the reproductive health of millions of women, remains relevant.

Conclusion. Most reasonable in diagnostics of endometriosis is a combination of different biomarkers that also minimizes false positive and negative results in differential diagnosis.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):371-376
Prospects in treatment of multiple sclerosis: near future
Sheiko G.E., Belova A.N., Kudykin M.N.

Multiple sclerosis (MS) is a widespread dysimmune-neurodegenerative disease of the central nervous system of unclear etiology. Despite significant achievements in the therapy of MS, the level of progressing disability and early mortality remains alarmingly high. The main aim of the given review is to give a detailed description of new promising medical drugs for treatment of MS. In the article the data of preclinical and clinical trials are given, presumptive mechanisms of the medical drugs under development are described. Development of new therapeutic approaches in treatment of MS is of great interest in modern science. The given review highlights new methods of treatment that are now undergoing clinical trialы and will probably come to the clinical practice in the near future.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):377-390
Statement of death in Russian legislation (critical analysis of article 66 of federal law «On fundamental healthcare principles in the Russian Federation» of 21.11.2011 №323-FL)
Boyko I.B.

Aim. Analysis of some controversial provisions of Article (Art.) 66 «Determination of the Moment of Death of a Person and of Termination of Resuscitation Activities» of Federal law «On Fundamental Healthcare Principles in the Russian Federation» of November 21, 2011 №323-FL (FL 323) directly concerning the issue of death of a person, and justification of making amendments to the title and text of the above mentioned norm.

Due to the absence of definition of the concept of «death» in FL 323, the author presents his own definition of death of a person. The used term «the moment of death of a person» as a determinant/indicator of the occurrence of death seems to be erroneous. This term cannot be extended to the fact of biological death. Under FL 323, death of the brain is considered to be equivalent to death of a person and today is inextricably linked with organ transplantation. However, in reality it is not so, and in this sense it is a typical juridical fiction that justifies legal removal of organs from living patients. Amendments to the title and wording of Article 66 FL 323 are proposed.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):391-398
Письмо в редакцию
Role of exosomes in diagnosis and therapy of prostate cancer
Fontana F., Babenko O.A.

Aim of this letter is to attract the attention of journal readers to the study of exosomes as an important direction in the development of Oncology, in particular, in the diagnosis and treatment of prostate cancer. Exosomes are produced by tumor cells and regulate proliferation, metastasis, and the development of chemoresistance. Their extraction from biological fluids allows further use of these vesicles as potential biomarkers of prostate cancer. In the future, exosomes can be successfully used in the delivery of drugs and other anti-tumor substances to cancer cells.

I.P. Pavlov Russian Medical Biological Herald. 2020;28(3):399-405

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