Vol 26, No 4 (2018)

Original researches
A study of the effect of complexes of 3d-metal ions with gluconic acid on synthesis of cytokines in experimental immunodeficiency
Knyazeva O.A., Urazaeva S.I.

Aim. Evaluation of the influence of synthesized gluconates of 3d-metals on production of cytokines in blood serum of mice with experimental immunodeficiency.

Materials and Methods. The effect of complex compounds of bivalent 3d-metals (Mn, Fe, Co, Cu, Zn) with glucuronic acid on production of cytokines: interleukin (IL)-1β, IL-6, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) in blood serum of mice with experimental immunodeficiency induced by a single intraperitoneal administration of cyclophosphamide at the dose of 50 mg/kg was studied. 3d-Metal gluconates (10-2mol/l) were orally introduced for comparison with immunostimulatory drug «Licopid®» and calcium gluconate (doses were calculated according to the instructions) daily for two weeks, starting from the second day after the injection of cyclophosphamide. Levels of cytokines were determined by immunoenzyme analysis.

Results. On the 16th day after the induction of immunodeficiency, levels of cytokines in blood serum of mice decreased: IL-1β – by 75.0%, IL-6 – by 65.2%, IFN-γ – by 61.6%, TNF-α –by 55.6% (p<0.05). Stimulatory effect of gluconates of 3d-metals on synthesis of cytokines depended on the used metal: the effect of MnGl, FeGl, CoGl, CuGl was lower than of licopid. ZnGl produced a weaker effect than licopid only on synthesis of IL-6, and equal effect on secretion of IL-1β and IFN-γ, and the highest effect on TNF-α (p<0.05 for all comparisons). Calcium gluconate did not produce any significant effect on the content of cytokines.

Conclusion. The obtained results show a significant role of 3d-metals in maintenance of immune homeostasis, which, taking into account the literature data, may be explained by their action through activation of the nuclear transcription factor NF-κB which controls expression of cytokines.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):459-465
P-glycoprotein functional activity in «soviet chinchilla» rabbits during pregnancy
Popova N.M., Shchulkin A.V., Chernykh I.V., Esenina A.S., Gradinar M.M., Nikiforova L.V., Ryabkov A.N., Yakusheva E.N.

P-glycoprotein (Pgp, ABCB1-protein) is a membrane transporter protein that plays the key role in pharmacokinetics of drugs with a broad spectrum of action. Substrates of this transporter are some medical drugs (antibacterial, antiretroviral, hypotensive) that are prescribed to pregnant women for long-term intake, sometimes throughout the whole gestation period.

Aim to study the activity of Pgp on the organism level in rabbits of Soviet Chinchilla breed in pregnancy.

Materials and Methods. The study was performed on 21 Soviet Chinchilla female rabbits (3000-3500 g). The animals were divided into 3 series. The first series (n=6) included rabbits with 7 days of pregnancy; the second series (n=5) − animals with 14 days of pregnancy; the third series (n=10) − rabbits with 21 days of pregnancy. 7 Days before the study and in the indicated gestation periods, functional activity of Pgp was assessed by the pharmacokinetics of marker transporter substrate – fexofenadine, after its single oral introduction (67.5 mg/kg). Besides, serum concentrations of progesterone, estradiol, testosterone and prolactin were determined by radio immune method

Results. In all the studied gestational periods, serum concentrations of estradiol, testosterone and prolactin did not significantly differ from those before pregnancy, but the level of progesterone in blood serum was significantly elevated above the norm. On the 7th day of pregnancy pharmacokinetic parameters of fexofenadine did not show any reliable changes as compared to the initial va-lues. On the 14th day of pregnancy a reliable increase in Cmax, AUC0-t, T1/2 of fexofenadine was noted as compared to the parameters before pregnancy, which indicates a decrease in Pgp functional activity on the organism level. On the 21st day of pregnancy Cmax of fexofenadine remained elevated. Other pharmacokinetic parameters of fexofenadine did not show reliable changes. Conclusion. Reduction in Pgp functional activity, determined by the pharmacokinetics of its marker substrate (fexofenadine), was noted in rabbits of Soviet Chinchilla breed on the 14th and 21st days of pregnancy with the underlying significant increase in progesterone level.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):466-473
Study of consumption frequency of the main sources of lycopene and its quantification in students’ diet
Kirpichenkova E.V., Korolev A.A., Onishchenko G.G., Nikitenko E.I., Denisova E.L., Fetisov R.N., Petrova E.S., Fanda E.A.

Aim. Comparative characteristics of the level of alimentary admission of lycopene and analysis of the frequency of inclusion of the main sources of lycopene in the diet of students of different age and sex.

Materials and methods. To study the frequency of inclusion in the diet of food sources of lycopene and its quantitative assessment, specially designed questionnaires were used, in which products with a significant content of lycopene were included.

Results. Comparative analysis of the levels of lycopene did not reveal significant differences between the percentages of men and women (φemp< φcr at P<0.05) in the groups with high level of intake. In all gender groups, the leading sources of lycopene are fresh tomatoes, ketchup and tomato-containing fast food products (pizza, lasagna, pasta and sandwiches). Evaluation of the results of the frequency method shows that more often than other sources in the weekly diet of students, regardless of gender, there are fresh tomatoes, ketchup and sandwiches. Analysis of the levels of lycopene intake in 1st and 5th year students did not reveal significant differences in all groups of consumption (φemp< φcr at P<0.05), except for the group with the intake of lycopene in the amount of 50.0-74.9% of the recommended, which is dominated by 5th year students. Sources of lycopene in students of different age groups do not differ - the main contribution to the recommended level is made by fresh tomatoes, ketchup and tomato-containing fast food products.

Conclusions. In 39.8% of students, due to the presence in the diet of fresh tomatoes, ketchup and tomato-containing fast food products, the recommended daily intake of lycopene was achieved. At the same time, 29.6% of the respondents did not have registered sources of lycopene in their diet; and 16.7% of the respondents included them in the diet in an insufficient amount, thereby ensuring the intake of lycopene in the amount of less than half of the recommended level. Most often, the weekly diet included fresh tomatoes, ketchup and tomato sandwiches. Watermelon, pink and red grapefruit, persimmon in the diets of the most of participants were absent.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):474-483
Experimental study of effectiveness of ear protection devices for prevention of intense noise exposure
Kharitonov V.I.

Occupational neurosensory deafness is one of central problems in the occupational medicine. Hearing loss associated with professional activity is the leading occupational disease with the permanently increasing share. In the industries with a very high level of noise it is recommended to use a combination of earplugs and earmuffs, and to control the condition of the ear analyzer, which provided a 3-fold increase in regular use of anti-noise earplugs.

Aim. To evaluates effectiveness of sound damping capacity of ear protectors and of their combinations on exposure to intermittent and impulse noise.

Materials and Methods. Several types of ear protectors of domestic and foreign manufacture were studied: earplugs of Berushi (Russia) and EAR (Great Britain) types, ShZO-1 earmuffs (Russia) and also earmuffs in conjunction with KKA helmet (Russia). The study was conducted in compliance with the rules and regulations of the effective standards and methodical instructions in the conditions of laboratory experiments and of real production. In the experiment, noise exposure was modeled in anechoic acoustic chamber, after which audiometric research was conducted on test subjects. In real industrial conditions, dimension of levels and noise exposure at the workplaces and the condition of the auditory analyzer of workers were controlled. For subjective evaluation of the design and comfort of the used ear protecting devices and their combinations, questionnaire-based survey was conducted.

Results. The results of the laboratory experiment and research work in the conditions of the real production permit to suggest high effectiveness of the evaluated ear protectors and of their combinations, and, taking into the account the criterion of preservation of hearing, the quality of hearing protection can be characterized as «good». Questionnaire survey of test persons showed a high sound damping capacity and convenience of the tested ear protectors and permitted to compile the data bank of comments and proposals concerning convenience of their use and their design.

Conclusions. Laboratory and industrial studies showed a high effectiveness of the tested ear protectors and the possibility of their practical use in the conditions of real production with exposure to extreme levels of intense impulse noise, with the obligatory permanent monitoring of correctness and timeliness of their application.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):484-492
Quality of life in patients with chronic kidney disease
Gulov M.K., Abdulloev S.M., Rofiev K.K.

Aim to study the quality of life (QOL) of patients with chronic kidney disease (CKD) in the Republic of Tajikistan.

Materials and Methods. The study was conducted in 2016-2018 and included 319 patients, with CKD (of them 58.9% men, with CKD I-IV stages – 121, receiving long term hemodialysis – 109, after kidney transplantation – 89) and 103 relatively healthy individuals (control group, men – 53.4%). The main causes of CKD were glomerulonephritis, diabetes mellitus, and pyelonephritis. QOL was evaluated by the SF-36.

Results. Impairment of the quality of life in patients with CKD was demonstrated in most parameters, both in comparison with the control group and with progression of CKD. In the terminal stage of CKD the quality of life evaluated by some parameters (bodily pain, general health, physical health, social functioning) was lower in patients dependent on program hemodialysis than in patients after kidney transplantation. The parameters of mental and psychological health did not show any differences between these groups which is explained by the authors as due to lack of psychological support after surgical intervention, to necessity of using immunosuppressive therapy and to the economical constituent of treatment.

Conclusions. Evaluation of the quality of life should be an obligatory component of the analysis of the quality and effectiveness of management of patients with chronic kidney disease including those at the terminal stage. In the work, impairment of the quality of life and of its separate parameters in progression of chronic kidney disease was objectively demonstrated. At the terminal stage, the quality of life evaluated by some most important parameters was lower in patients receiving program hemodialysis that in patients after transplantation of kidney.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):493-499
Endothelial dysfunction and platelet function disorder in hemostasis in development of hepatic fibrosis in children with autoimmune hepatitis
Konovalova E.Y., Lavrova A.E., Presnyakova M.V.

The purpose is: To assess the clinical relevance of the endothelial condition and platelet aggregation in the development of hepatic fibrosis in children with autoimmune hepatitis.

Materials and Methods. 35 patients aged from 3 to 17 years old were studied, including 19 girls - (54%) and 16 boys - (46%). The 1st group consisted of 17 children with the degree of fibrosis F 0-2 acc. to the METAVIR score; the 2nd group consisted of 18 patients with the degree of fibrosis F 3-4 (METAVIR) acc. to the METAVIR score based on the indirect elastometry data in children of the 2nd group hepatic cirrhosis was diagnosed; the control group consisted of 15 children with health group I or II. The endothelium state and the platelet aggregation activity were assessed in all the patients. To test statistical hypotheses, the Mann-Whitney U test, the Spearman correlation coefficient and the Fisher criterion were used. The critical value of the significance level is assumed to be 0.05. Quantitative data are presented as: median and the first; third quartile of Me (Q1; Q3).

Results. In children with autoimmune hepatitis some signs of the various-degree fibrosis formation were revealed in the ¾ of the examined. Patients of the 2nd group have a more aggressive course as compared to the 1st group: in the disease debut there were mainly expressed asthenoneurotic complaints (p = 0.021), manifestations of the jaundice syndrome (p = 0.014), more frequently hepatic-cell insufficiency (p = 0.045) is diagnosed and followed by complications of the disease (hypersplenism (p = 0.014), varicose veins of the esophagus (p = 0.003)). All children with autoimmune hepatitis have the endothelial dysfunction, the enhancing platelet aggregation activity. The degree of fibrosis correlates with the concentration of endothelin-1 (r = 0.4, p = 0.004), the von Willebrand factor (vWF) activity (r = 0.5, p <0.001), the platelet count (r = -0.5, p = 0.003). The determination of the endothelin-1 concentration, the von Willebrand factor activity and the platelet count may be used to assess the hepatopathy severity in children with autoimmune hepatitis.

Conclusion. In children with autoimmune hepatitis the endothelial dysfunction and platelet disorders are revealed in the hemostasis system correlating with the severity of the pathological process.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):500-510
Effectiveness of mediastinal lymphadenectomy in surgical treatment of generalized destructive pulmonary tuberculosis
Papkov A.V., Giller D.B., Dobin V.L.

Bronchopleural complications after pneumonectomy in generalized destructive tuberculosis are associated with the presence of intrathoracic lymph nodes (ITLN) with caseous alterations.

Aim. To improve the effectiveness of surgical treatment of patients with generalized destructive pulmonary tuberculosis by development and introduction of the method of mediastinal lymphadenectomy in tuberculous lesion of mediastinal lymph nodes.

Materials and Methods. Results of surgical treatment of 515 patients with generalized destructive pulmonary tuberculosis were analyzed. In 274 of them the surgical treatment was supplemented with mediastinal lymphadenectomy (the main group). In the control group (241 patients) only resection was performed without removing lymph nodes.

Results. Analysis of the postoperative course of the disease in both groups of patients (with mediastinal lymphadenectomy and without it) showed that bronchopleural complications occurred in 7 (2.6%) cases in the main group and in 30 (12.4%, p<0.05) cases in the control group. In the main group exacerbation of the specific process was noted in 1 patient (0.4%), and in comparison group in 9 patients (3.7%, p<0.05). Elimination of macroscopically altered ITLN in widespread destructive tuberculosis permitted to reduce the complications rate in the postoperative period by 64.8% (p<0.05). Indications to removal of IHLN included: a) enlargement of ITLN (>2 sm) and in duration; b) fusion with the surrounding tissues, softening of the node tissue in its caseous melting, c) existence of yellowish or whiter in comparison with the surrounding tissue inclusions in the node being manifestations of tuberculous granuloma. In histological, cytological and bacteriological examination, these macroscopic signs in 97% of cases indicated active tuberculosis of mediastinal lymph nodes.

Conclusions. In 97% of cases, widespread destructive secondary pulmonary tuberculosis runs with an active specific process in mediastinal lymph nodes which makes it reasonable to perform a selective lymphadenectomy in such group of patients. Secondary damage of different groups of intrathoracic lymph nodes by the active process depended on localization of lung destructions and occurred along the routes of lymph drainage from them. Reliable signs of active tuberculous of ITLN include: more than 2.0 cm lymph node enlargement, in duration, periadenitis, fluctuation and in homogeneity. Removal of macroscopically altered intra-thoracic lymph nodes in widespread destructive pulmonary tuberculosis permits to reduce the rate of complications in the postoperative period by 64.8%.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):511-518
Prognostic value of genefusion proteins in prostatic cancer
Bezgodova N.V., Vtorushin S.V., Krakhmal` N.V., Purlik I.L., Latypov V.R.

Background. Currently, in the study of prostate cancer, much attention is given to specific molecular patterns reflecting the biological potential of the tumor. Of most interest is analysis of the proteins of chimeric genes in a tumor.

Aim of study is analysis of peculiarities of ERG and PBOV1 proteins expression in tumor cells and correlation of them with the prognostic parameters of the disease in patients.

Materials and Methods. The group of study consisted of 85 patients diagnosed with prostatic carcinoma (stage II-III of the disease, T1-3N1-2M0), after radical prostatectomy. No specific preoperative treatment was given. Histological examination was conducted using a standard method, and immunohistochemical one – with use of an automatic stainer. Morphological characteristics of the tumor, of distant regional lymph nodes and of seminal vesicles were evaluated. Correlation between the histological and expression parameters of tumor and occurrence of distant metastases was studied.

Results. Correlation was found between parameters of expression of the studied proteins with such variant of tumor progression as hematogenic metastasis. A higher percentage of expression of ERG and PBOV1markers in cells of prostate carcinoma correlates with a lower degree of tumor differentiation and with a poor prognosis for the course of the disease.

Conclusion. The results of the conducted research demonstrate significance of ERG and PBOV1 proteins as additional prognostic factors in patients with prostate carcinoma, and probably may be used for evaluation of prognosis of the disease in selection of the management tactics for the given category of patients.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):519-527
Clinical cases
Diffuse idiopathic skeletal hyperostosis: complexity of diagnosis in a patient with dysphagia and dyspnea
Loginov N.V.

In the article a rare clinical observation of a patient with diffuse idiopathic skeletal hyperostosis with damage to the cervical spine and pronounced dysphagia and dyspnea is presented. The described case vividly demonstrates difficulties in diagnosis and treatment tactics of this disease and raises the question of necessity of diagnostic alertness to the diffuse idiopathic skeletal hyperostosis in patients with progressive dysphagia and dyspnea, not only in those of aged and old age, but also in younger patients (the age of described patient was 56 years, while in 95% of cases described in the international literature, patients were above 60).

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):528-532
Clinical case of endovideoscopic treatment of choledocholithiasis complicated with mirizzi’s syndrome
Tarasenko S.V., Zaitsev O.V., Tyulenev D.O., Kopeikin A.A.

Mirizzi's syndrome is a rare and severe consequence of cholecystocholedocholithiasis, the treatment and diagnosis of which presents significant difficulties. The question of selection of the method of surgical treatment of choledocholithiasis, complicated with Mirizzi’s syndrome, still remains open today. The article describes a clinical case of choledocholithiasis, complicated with Mirizzi’s syndrome, and the original technique of its surgical treatment. The described clinical case is interesting from the point of view of demonstration of the original technique of endovideososcopic treatment of this disease.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):533-537
Chicken embryo as an experimental object for studying development of cardiovascular system
Kade A.H., Trofimenko A.I., Turovaia A.Y., Pevzner D.A., Lazarev V.V., Lysov E.E., Pogosyan S.A., Minina I.I.

Currently, congenital cardiovascular diseases, including congenital heart defects, contribute to the morbidity and mortality of children worldwide. In this regard, great importance is gained by experiments that allow studying the development of cardiovascular system (CVS).  The use of chicken embryos laid the foundation for an experimental study of both the physiology and pathology of the development of CVS. In virtue to accumulated theoretical and experimental material about pattern of development chicken embryos and their organs it becomes possible to study etiology and pathogenesis of many cardiovascular diseases. Due to the availability, large size, simplicity of manipulation and cultivation, chicken embryos served as a model for describing of the development and vascularization of the heart, and due to the high conservatism of many key mechanisms of early ontogenesis, the data obtained from such experiments could also be extrapolated to humans. Work with chicken embryos formed the basis for human knowledge in the field of embryogenesis of the cardiovascular system - the formation of the myocardium, epicardium, endocardium, coronary vascular bed, chambers of the heart and the main vessels. With the development of new biomedical technologies, primarily the techniques of intravital imaging, the range of possible interventions on the CCC of the chick embryo has expanded. Taking into account these advantages and the improvement of experimental methods, models based on chicken embryos do not lose relevance to this day.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):538-546
Influence of parental alcoholism on suicidal and personality-psychological characteristics of offspring
Baykova M.A., Merinov A.V.

This article is a review of literature data, devoted to the influence of alcohol dependence of parents on the suicidal and personality-psychological characteristics of their offspring. Despite a decline of the incidence of alcohol dependence in the population, in Russia about 15-50% of families can say that they have encountered the problem of an alcoholized parent. Adult children of alcoholics (ACAs) are a fairly extensive, highly autoaggressive stratum of society. This group of people is the most dangerous in terms of the frequency of development in them of various kinds of addictions, as well as the likelihood of committing a suicidal attempt. The purpose of this review was to present modern ideas about the suicidality of adult children of alcoholics, their socio-cultural characteristics, personality and psychological characteristics; to demonstrate the degree of influence of addictive parental figures on the antivitality of offspring and its formation. The analysis of English and Russian literature is carried out. We have convincingly demonstrated that the ACAs represents a group with an elevated, relative to normative population, autoaggressiveness, inclination to parasuicidal patterns, with difficulties in building relationships with the society and finding a place in it. Conclusions were made about the inadequacy of the studies conducted, the lack of accurate data on the transgenerational mechanisms of autoaggressive transmission to offspring, the factors influencing the heterogeneity of the ACAs a population-species group, the need to take into account the gender of both parents and the ACAs themselves.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):547-558
Variants of temporary mmobilization in jaw fractures
Mitin N.E., Rodina T.S., Strelkov N.N., Zolotova M.I., Volkova V.V.

In peacetime and in wartime, fractures of the bones of the facial skeleton are an important phenomenon (5-6% to 7-9% of all traumatic skeletal injuries) requiring use of rational treatment methods. The share of mandibular fractures accounts for 65-85%, of maxilla – 4-6%, of zygomatic and nasal bones – 7-9% and 4-7%, respectively. The need for immobilization is associated with the risk of development of pain and complications, such as bleeding, microbial contamination, asphyxia, injury of nerves and blood vessels. The article gives a comparative analysis of means of transport immobilization of jaws on examples of traumas received in the wartime and in emergency situations. There were chosen extraoral methods that hold jaw fragments with the help of bandage secured to the cerebral cranium, and intraoral methods with maxillomandibular ligature fixation.

Conclusion. Standard Entin head-chin strap has certain advantages over Hippocratic cap bandage and Pomerantseva-Urbanskaya method. It is sufficiently universal and may be adjusted to any size of the head, possesses sufficient strength and provides reliable fixation of jaws. Ivy’s method was found to have advantages in comparison with other methods of maxillomandibular ligature fixation, which are strong and high-quality immobilization of the jaw fragments, possibility of use with multiple fractures, simplicity of application. All this permits to recommend Ivy’s method for use in case of indications.

I.P. Pavlov Russian Medical Biological Herald. 2018;26(4):559-566

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