Home – Home – Jornals – Siberian Scientific Medical Journal 2019 number 6

The literature review, according to recent publications, systematizes modern ideas about new biochemical markers of bronchopulmonary pathology, namely chronic obstructive pulmonary disease, chronic bronchitis and bronchial asthma. Information on potential biochemical markers associated with pathology of the bronchopulmonary system is presented: pulmonary activation regulated chemokine (chemokine ligand CCL20), surfactant proteins A and D, pentraxin-3, defensins, alpha-1 antitrypsin, Clara cell protein, interleukin-19, resistin-like molecules. For each biomolecule, its characteristic, biological properties and effects are described, as well as the results of experimental and clinical studies of its effects in bronchopulmonary pathology, the association of elevated blood levels of a biomolecule with clinical manifestations of diseases. It is concluded that today there are a considerable number of new potential biomarkers of the respiratory system diseases for early and effective diagnosis, prevention and treatment of diseases, however, the effects of some of them are either insufficiently studied or contradictory and require further research, which is actively ongoing in the whole world and in Russia.

For the treatment of bipolar affective disorders, lithium preparations are the most famous and effective. But the main problem with the use of lithium preparations is the narrow «therapeutic corridor». An urgent task is the creation of dosage forms of lithium with a slow release and a wide therapeutic range. The study object was a new normotymic drug based on lithium, aluminum oxide and polymethylsiloxane. Due to the new carrier matrix lithium is released from its porous structure gradually providing a prolonged effect and maintaining an optimal concentration in the blood which also helps to minimize side effects. The purpose of the study was to explore the pharmacokinetic parameters of a normotymic drug based on a complex lithium citrate, aluminum oxide and polymethylsiloxane (LOAP). Material and methods: for the assessment of pharmacokinetic parameters the method of atomic emission spectrometry with inductively coupled plasma and two-chamber modeling were used. Results and discussion. The pharmacokinetic data showed a linear nature of pharmacokinetics of the drug based on LOAP as the foundation of data of the lithium’s amount in the blood plasma of rabbits after intragastric administration at doses of 200, 400 and 800 mg/kg. The drug with intragastric administration at a dose of 800 mg/kg is well absorbed from the gastrointestinal tract, with bioavailability (F) 74 %. This dose shows the maximum increase of the area under the pharmacokinetic curve (AUC - 32787.1 (ng × h)/ml), and indicators of elimination constant (K_el - 0.062 h^-1), clearance (Сl - 0.09 l/(kg × h)), elimination half-life (T_1/2β - 11.436 h) in comparison with other doses remain unchanged.

The research aim was to study the dynamics of biogenic amines in the brain, tumor and intact skin of urokinase (uPA) gene knockout mice on day 21 of the B16/F10 melanoma growth. Material and methods. The study included male and female uPA gene knockout (-uPA, n = 38) and wild type mice (+uPA, n = 61). Melanoma was transplanted subcutaneously. Levels of biogenic amines were studied by ELISA in tissues obtained on day 21 of carcinogenesis. Results and discussion. Intact (-uPA) mice showed an increased total content of biogenic amines: in the skin - due to noradrenaline increase by 4.8 times in males and by 4.9 times in females, histamine - by 3.6 times in males and by 1.6 times ( p < 0.05) in females, serotonin - by 3.4 times in males and by 8.3 times in females; in the brain - due to noradrenaline increase by 3.5 times in males and by 3.2 times in females, dopamine by 2.1 times in males and by 2.9 times in females, while histamine content decreased. Melanoma development in (-uPA) mice was characterized by: lower levels of adrenaline with high NA concentrations and an increase in the serotonin metabolism in the brain; higher histamine concentrations in the tumor and higher serotonin levels in the skin; similar to (+uPA) mice levels of adrenaline (males) and noradrenaline in the tumor and higher levels of adrenaline in the tumor and histamine in the skin in (-uPA) females. Conclusions. The uPA gene knockout limits the development of stress at the central regulatory level due to lower levels of A together with increasing serotoninergic mediation in the brain, as well as modulates the immune antitumor response due to higher levels of histamine in the tumor and 5 serotonin in the skin, as a result of lower monoamine oxidase activity, in mice with B16/F10 melanoma.

The paper deals with the functions of the main classes of blood plasma lipoproteins (LP) that are associated with the transport of cholesterol esters included in their composition. The aim of the study was to investigate the features of the uptake of cholesterol esters associated with plasma LP fractions (very low (VLDL), low (LDL), and high density LPs (HDL)) by rat organs and tissues, and to show the participation of various subfractions of HDL (HDL₂ and HDL₃) as specific cholesterol carriers in the main steroid-producing organs of rats. Material and methods. The in vivo studies with intravenous LP injection of ¹⁴C labeled cholesterol oleate (¹⁴C-OCh) associated with plasma LP fractions have been carried out. Results. Intravenous injection of a ¹⁴C-OCh) in the composition with VLDL led to the maximal mark uptake by the liver. Three times less uptake of labeled cholesterol was observed in the adrenal glands, testes and heart muscle. In other tissues radioactivity gradually decreased in the raw: spleen > lungs > kidneys > thyroid gland and adipose tissue. After the injection of ¹⁴C-OCh in the composition of LDL marked predominant uptake of the label by the adrenal glands, testes, and liver. A feature of the use of HDL as a carrier platform for ¹⁴C-OCh is the high accumulation of label in steroid-producing organs: the adrenal glands and testis. The dynamics of uptake of ¹⁴C-OCh in the composition of HDL by the adrenal glands and testes of rats in different time intervals after injection (30 min, 3, 6 and 12 h) was studied. Adrenal cells actively uptake ¹⁴C-OCh from HDL, as a result of which the radioactivity of the tissue increased rapidly and after 30 minutes almost reached its maximum. In contrast to the adrenal glands uptake of the testis was characterized by a gradual increase in radioactivity with a maximum of 6 hours and a rather sharp decrease to 12 hours from the beginning of the experiment. In vitro experiments showed the differences in the effect of HDL₂ and HDL₃ on the corticosterone production by the adrenal glands of rats. Conclusions. The paper presents the features of uptake of cholesterol esters by organs and tissues of rats depending on the used LP-transporter (VLDL, LDL, HDL). In addition, the results suggest that HDL₃ subfraction may be the more preferred source of cholesterol for steroid synthesis in the adrenal cortex of rats compared to HDL₂ subfraction.

The aim of this work was to design and study biological properties of the recombinant human granulocyte colony stimulating factor (G-CSF), «linked» to apolipoprotein A-I (apoA-I) by a peptide linker, for obtaining in perspective a prolong form of the drug based on this cytokine. Material and methods. The nucleotide sequences of the genes encoding G-CSF and apoA-I were designed and optimized for expression in Pichia pastoris yeast using several computer programs. The assembly of the gene coding for the G-CSF-аpoA-I chimeric cytokine, its cloning in the pPICZα-A vector, and expression in P. pastoris cells were performed using standard genetic engineering methods. Purification of the chimeric cytokine was carried out by two-stage ion-exchange chromatography. The biological activity of the chimera was determined in vitro on rat and human bone marrow cells (BMC) using flow cytometry, cell cycle analysis and myelograms. Results. A recombinant P. pastoris X-33 yeast strain producing a chimeric cytokine containing the amino acid sequence G-CSF from the N-terminus, and mature human apoA-I from the C-terminus was constructed. In experiments on BMC of rat, it was shown that G-CSF-аpoA-I increases the number of granulocytes in 1.8-2 times less compared with G-CSF. At the same time, the chimeric cytokine maintained the viability of monocytic and lymphocytic cells. Unlike G-CSF, the chimera increased the number of blast cells and normalized neutrophil segmentation, reducing the number of anomalies 1.5 times more efficiently. Conclusion. A new chimeric cytokine G-CSF-аpoA-I was constructed, exhibiting the properties of not only a colony-stimulating factor, but also a growth factor, supporting the viability of other types of BMC.

Aim of the study was to compare the distinct types of progressive hematoxylin stains and to optimize the protocols of hematoxylin and eosin staining of blood vessels, heart, liver and spleen. Material and methods. Heart (ventricles), abdominal aorta, liver (right lobe) and spleen (left part) of the Wistar rats were excised, fixed in 10% neutral phosphate buffered formalin for 24 h, washed in tap water for 2 h, dehydrated in ascending ethanol series (70 %, 80 %, and 95 %) and isopropanol, embedded into paraffin and then sectioned (5 μm) using rotary microtome. Staining was performed using Mayer’s, Gill’s, or Carazzi’s hematoxylin during 2, 5, or 15 minutes and 1 % alcoholic/aqueous eosin for 2 minutes without differentiative solution. Results were assessed by three independent histologists. Results. All examined progressive hematoxylin stains had their distinctive features. Mayer’s hematoxylin demonstrated the most intensive nuclear staining; however, staining for 15 minutes could lead to the bluing of cytoplasm and extracellular matrix. In contrast, Gill’s hematoxylin was characterized by less intensive nuclear staining and achieved clear blue-violet shade only after 15 minutes of staining. Carazzi’s hematoxylin showed balanced coloration of nuclei and cytoplasm/extracellular matrix and did not change the red/pink shades of eosin, yet the intensity of nuclear staining was less as compared to Mayer’s hematoxylin. Short-term (2 minutes) staining was insufficient to reach intensive nuclear staining. Conclusion. The optimal hematoxylin and eosin staining protocol is to use eosin for 2 minutes following staining by Carazzi’s hematoxylin for 15 minutes (for aorta), Carazzi’s or Gill’s hematoxylin for 15 minutes or Mayer’s hematoxylin for 5 minutes (for liver), Carazzi’s or Gill’s hematoxylin for 15 minutes (for heart), and Carazzi’s hematoxylin for 5 minutes (for spleen).

Co-occurrence of cardiovascular diseases is significantly common among patients with bronchial asthma. Genetic factors can have a significant effect on the development of hypertension in patients with asthma. Objective of the study was to investigate the associations of polymorphic variants relating to quantitative changes in the expression profile (eQTL) of the CAT , TLR4 , and IL10 genes with the development of bronchial asthma co-morbid with arterial hypertension. Material and methods. Genotyping of 48 eQTL SNPs of the CAT, TLR4 , and IL10 genes was performed using MALDI-TOF mass spectrometry in patients with «isolated» asthma ( n = 145) and arterial hypertension ( n = 144) and their combination ( n = 146), as well as in the control group of healthy individuals ( n = 152). Using logistic regression, an analysis of the associations of haplotypes with the studied diseases was carried out. Results. An association of bronchial asthma in combination with arterial hypertension with haplotypes formed by eQTL SNPs of the CAT and TLR4 genes was established. The spectrum of haplotypes associated with comorbidity of asthma and hypertension differs from the haplotypes associated with “isolated” asthma. Conclusion. The molecular base of asthma and hypertension comorbidity can be associated with variants that control the expression of TLR4 and CAT genes.

The purpose of our study was to improve the quality of life of patients after surgery for oral and oropharyngeal cancer. Material and methods. Voice rehabilitation outcomes in 50 patients with stage II-III oral and oropharyngeal cancer were studied. All patients underwent resection of ½ of the tongue. The patients were aged between 33 and 70 years, 70 % of them were up to 60 years. All patients received combined modality treatment and postoperative voice rehabilitation in Cancer Research Institute of Tomsk National Research Medical Center of RAS. The technique of voice rehabilitation included breathing exercises, articulation gymnastics for the muscles of the cheeks, lips, tongue, lower jaw and correction of disturbances in sound pronunciation. A speech function was assessed before and after rehabilitation using speech material that contained a text with semantic load, individual words, syllables and a meaningless set of sounds. Results and discussion. In the postoperative period, all patients experienced a sharp restriction of the mobility of the stump of the tongue, very low speech intelligibility, violation of the pronunciation of sounds, complete or partial absence of intonation pattern, and slowdown in the rate of speech. Postoperative voice rehabilitation aimed at increasing the mobility of tongue stump and correcting sound pronunciation made it possible to improve speech function in the period from 5 to 30 days (median 22.1) by restoring the pronunciation of the velar sounds [K, G] in 78-94 % of cases, alveolar sounds [T, D] in 74-80 %, and whistling sound [C] in 56 % of cases. Based on the study, the authors conclude that speech rehabilitation is required for all patients, who underwent surgery for oral and oropharyngeal cancer, taking into account the extent of surgery and individual characteristics of the patients.

The purpose of the study is to assess the contribution of senile asthenia level to hemorrhagic complications quantity in elderly patients with atrial fibrillation (AF) taking direct oral anticoagulants (DOAC). Material and methods. Elderly patients ≥75 y.o. with AF taking dabigatran, apixaban or rivaroxaban in full or reduced dosages and without special features of bleeding (such as double and triple antithrombotic therapy) were included in the study. If a patient was under anticoagulants before the study (but not earlier than one became 75 y.o.), this experience was also analyzed. All bleedings during the first 18 months of anticoagulating were taken in mind. Patients in different DOAC groups were comparable in age and concomitant pathology. The «fragility» index was evaluated at the stage of inclusion in the study; an adapted Rockwood scale was used. Results and discussion. 102 patients with AF ≥75 y.o. taking dabigatran, apixaban or rivaroxaban in dosages corresponding to the instructions were included in the study. During the analyzed period, 19 small clinically significant hemorrhagic events that did not require hospitalization or cancellation of DOAC were recorded. Patients with and without bleeding in anamnesis were significantly differed only by «fragility» index score ( р = 0,001). The differences between concomitant pathology level which are mentioned in scale, is also not statistically significant. The average age of patients with and without bleeding anamnesis was not also significantly different ( p = 0.12). In the future, it is advisable to continue the study using several scales for assessing the severity of the «fragility» index. Thus, it is advisable to calculate the «fragility» index in patients ≥75 years of age with AF taking DOAC.

The purpose of the study was to examine the characteristics of the content of cytokines in the peritoneal fluid in women of reproductive age with infertility against the background of chronic inflammatory diseases of the pelvic organs in the stage of clinical remission. Material and methods. A study was conducted of 50 patients aged 23-36 years with a verified diagnosis of infertility of tubal peritoneal genesis against a background of chronic inflammatory diseases of the reproductive sphere in the stage of clinical remission. As a control group, 15 practically healthy women aged 25-37 years were examined. Concentration of cytokines TNF-α, IL-4, IL-6, IL-10, IFN-γ, MCP-1 in the peritoneal fluid was measured by enzyme-linked immunosorbent assay. Results and discussion. In the main group of patients with tubal-peritoneal infertility, the activity of local inflammatory reactions is tested in the period of clinical remission of a chronic inflammatory process. This is confirmed by a significantly higher level of TNF-α, IL-4, IL-6, IFN-γ, MCP-1 in the peritoneal fluid compared to the control group. The studied biologically active substances play a significant role in the development of the immune response, as well as fibroplastic processes. The results can be regarded as the latent development of the immune response in reactions to constant antigenic stimulation from the focus of chronic inflammation, which is a significant factor in the development of adhesions in the formation of infertility, and requires the inclusion of immunotropic therapy methods in treatment.

Objective of the study was to assess the diagnostic significance of hemodynamic disorders in the area of carotid and vertebral arteries in patients with hypertension combined with benign paroxysmal positional vertigo (DPPG) using ultrasound duplex scanning of neck vessels. Material and methods. Thirty eight patients of the clinic of Federal Research Center for Fundamental and Translational Medicine with hypertension and concomitant dizziness were examined. The state of carotid and vertebral arteries, blood flow in the arteries were assessed by duplex ultrasound scanning using the Vivid E9 apparatus. Results and discussion. The influence of the blood flow at the level of carotid and vertebral arteries on the severity of clinical symptoms of dizziness in patients with hypertension with concomitant DPPG was shown. The clinical significance of atherosclerotic changes in carotid arteries, tortuosity of carotid and vertebral arteries of the effectiveness of treatment and prevention of dizziness in patients with hypertension and DPPG was revealed. It is shown that in patients with hypertension and comorbid DPP, the severity of the relationship of hemodynamically significant changes in the carotid and vertebral arteries with clinical manifestations of dizziness is greater than in patients with hypertension without DPP. The use of ultrasound duplex scanning of brachiocephalic arteries in hypertension with comorbid vertigo allows for differential diagnosis of benign paroxysmal positional vertigo and cerebrovascular dyscirculatory disorders, the degree of their participation in clinical manifestations of dizziness. A new medical technology for the diagnosis of pathogenic mechanisms of dizziness in patients with hypertension, using ultrasound duplex scanning of carotid and vertebral arteries, allows to personalize treatment and prevention in such patients.

The paper presents the case of clinical observation of a patient with atypical hemolytic-uremic syndrome (aHUS). aHUS is a disease characterized by an unfavorable prognosis (severe or catastrophic course with rapid development of terminal renal or multi-organ failure). The aim of the study is to evaluate the approaches to differential diagnosis of aHUS in clinical practice. Material and methods . The study was conducted on the basis of the Nephrology Department of Kemerovo Regional Clinical Hospital n.a. S.V. Belyaev. The clinical observation of patient D., aged 26 years old, is discussed. Results and discussion. Diagnosing aHUS requires: 1) diagnosing thrombotic microangiopathy (TMA: thrombocytopenia or decrease in platelet count by more than 25 % of original, visceral damage (kidneys, CNS, gastrointestinal tract, heart, lungs)); 2) ruling out HUS associated with Shiga toxin-producing Escherichia coli (STEC-HUS; negative for Shiga-toxin in blood and stool), thrombotic thrombocytopenic purpura (TTP), systemic connective tissue disease, catastrophic antiphospholipid syndrome, HIV infection; 3) assessing the activity of ADAMTS13 (decrease confirms the aHUS diagnosis); 4) proving normal content of complement components C3 and C4 as an additional argument in favor of aHUS diagnosis. At the first stage, the patient was diagnosed with TMA (platelet content 37 × 10⁹/l, hemoglobin content 59 g/l), LDH up to 824 E/l), liver damage (AST, ALT and LDH activity 55, 60 and 824 U/l, respectively), kidney damage (acute renal damage), lungs, heart, and brain damage. At the second stage the following diagnoses were ruled out: STEC-HUS (Shiga toxin in blood and stool was not detected), TTP (ADAMTS13 activity level was 66 %, whereas reference values are 93-113 %, in TTP - below 5-10 %); systemic connective tissue diseases catastrophic antiphospholipid syndrome, HIV infection sepsis. Normal values of C3 (0.9 g/l) and C4 (0.23 g/l) complement components did not rule out the diagnosis of aHUS.

Aim of the study was to determine the level of self-assessment of health-related quality of life (HRQoL) and its relationship with the objective state of health in students of junior courses of medical and humanitarian specialties. Materials and methods. The study has been conducted at the Far Eastern Federal University (FEFU) and at the Pacific State Medical University (TSMU) since December 10, 2017 to June 10, 2018. It was attended by 479 students of junior (1-3) courses, of which 228 (47.5 %) studied medical specialties at FEFU and TSMU, 251 (52.5 %) studied humanitarian specialties (FEFU). The average age of students was 19.5 ± 1.9 years, the average response rate - 94.2 %. The selection was carried out using the principles of gender-stratified randomization. The state of health of the students was assessed by the presence of chronic diseases and the level of the Charlson comorbidity index. In the collection of data used outpatient cards (Form 025/y); patient registration logs (Form 001-1/y); medical control cards of follow-up (Form 062/y). For the self-assessment of HRQoL, a questionnaire was used: «A short form of self-assessment of HRQoL, MOS SF-36v2» (Medical Outcomes Study Short Form version 2). The demographic and socio-economic status was determined using a special questionnaire. Results and discussion. HRQoL indicator in medical students turned out to be related to the frequency of seeking medical help ( r = 0.75; p < 0.01), the comorbidity index ( r = 0.43; p < 0.05) and the average number of chronic diseases among respondents ( r = 0.49; p < 0.05). The relationship between the total HRQoL and the physical and mental components of QoL self-assessment also proved to be quite strong ( r = 0.69; p < 0.01; r = 0.59; p < 0.01, respectively). In students of humanitarian specialties HRQoL appeared (in addition to the physical and mental component of QoL) to be interrelated only with the average number of chronic diseases ( r = 0.69; p < 0.05). Thus, 76,0 % of students of medical and humanitarian specialties have undergone chronic diseases of internal organs in junior courses. Diseases of the digestive (30-33 %), urogenital (10-14 %), respiratory (7-10 %) and nervous systems (6-10 %) are most common in the student environment. HRQoL in the students of junior courses of medical and humanitarian specialties does not significantly differ and is rated by them as satisfactory.

The shortage of medical personnel, primarily in the district service and rural health care, the insufficient effectiveness of measures taken by the state to solve the personnel problem («presidential» allowance for the district service, the program «Zemsky doctor», etc.) indicate the insolvency of personnel policy in the industry. The state spending huge budgetary funds for training specialists deprived itself of the right to use them where they are urgently needed. The desire to improve the quality of training of medical students on the basis of accession to the Bologna agreement did not give the desired result. The availability of medical care is also limited by the fact that in the general structure of medical specialties, the number of doctors of clinical specialties, i.e. those who directly work with patients is significantly lower than in the EU and their share continues to decline. All of the above suggests that the Ministry of Health has no clear idea about the issue of personnel, is not formed the system able to solve it, which must include: career counseling - training - public distribution trained on a budgetary basis - professional development - career growth. The state and the leadership of the regions should create favorable conditions for work and life, attracting specialists, as well as interesting them in long-term work at the place of distribution. On the basis of the Soviet experience in the organization of personnel work in health care, best practice of other countries, the authors propose measures in the medical personnel training improvement, in attracting and long-term interest in their work in «problem» positions (district service, rural health care, etc.).