Vol 19, No 3 (2019)

Venous return and pulmonary hemodynamics under the positive end-expiratory pressure mechanical ventilation
Evlakhov V.I., Poyassov I.Z.

In the review we have discussed the mechanisms of the changes of the venous return and pulmonary hemodynamics which take place in clinical cases of the mechanical lung ventilation with positive end-expiratory pressure. In these conditions the elevating of right atrial pressure does not cause the decreasing of the venous return, because the mean circulatory filling pressure also increases. Thus, the gradient for venous return remains relatively constant. In case of the mechanical lung ventilation with positive end-expiratory pressure the decreasing of the venous return is the result of the elevation of the venous resistance as consequence of the direct increasing of the intrathoracic and transdiaphragmatic pressures and activation of the reflectory neurogenic mechanisms. In the conditions, indicated above, the increased alveolar pressure leads to the improvement of the diffused lung capacity for oxygen, which decreases the manifestations of the hypoxic pulmonary vasoconstriction and thus — diminishes pulmonary vascular resistance. The character of changes of the last one is determined by the reactions of the two types (alveolar and extraalveolar) intraparenchimal pulmonary vessels. This leads to the changes of the resistive and capacitive functions of the pulmonary vessels. In case of the high levels of the positive end-expiratory pressure (more than 30 cm of water column) the value of alveolar pressure is comparable or even more excessive than pulmonary artery pressure (12–16 mm Hg), which can be the reason of the decreasing of the right ventricular contractility and the venous return. The increasing of the capillary filtration coefficient of pulmonary vessels in the conditions of the mechanical lung ventilation with positive end-expiratory pressure can be the result of the activation of the mechanosensitive transient receptor potential vanilloid-4 (TRPV4) channels and the increasing endothelial calcium entry.

Medical academic journal. 2019;19(3):11-20
Dynamics of age-related structural and functional changes in the brain of patients with autism spectrum disorders
Belokoskova S.G., Malsagova E.M., Tsikunov S.G.

The review reflects modern information on the brain dysontogenesis of patients with autism spectrum disorders throughout life. The features of the stages of age-related disorders of the structure and functional state of the brain of such patients are presented. Along with the description of defects in the morphofunctional organization of the brain of patients, attention is focused on the presence of individual differences of such defects, which determines the heterogeneity of the clinical manifestations of the disease.

Medical academic journal. 2019;19(3):21-26
SAS Enterprise Guide 6.1 for physicians: getting started
Bunenkov N.S., Bunenkova G.F., Beliy S.A., Komok V.V., Grinenko O.A., Nemkov A.S.

Objective. To develop algorithm of data analysis of prospective non-randomized clinical trial AMIRI–CABG (ClinicalTrials.gov Identifier: NCT03050489) using SAS Enterprise Guide 6.1.

Materials and methods. Data collection was performed according prospective non-randomized clinical trial AMIRI–CABG in Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia between 2016–2019 years with 336 patients. There is database with clinical, laboratory and instrumental data. Statistical analysis was performed with SAS Enterprise Guide 6.1.

Results. There was developed algorithm of data analysis of prospective non-randomized clinical trial AMIRI–CABG. This algorithm could be useful for physicians and researchers for data analysis.

Conclusion. Presented algorithm of data analysis could make easier and improve efficient data analysis. SAS Enterprise Guide 6.1 allows fast and accurate process big data.

Medical academic journal. 2019;19(3):27-36
Basic studies
Early protection against influenza by pandemic live attenuated influenza vaccines
Rekstin A.R., Desheva J.A., Kiseleva I.V., Isakova-Sivak I.N.

Live attenuated cold-adapted (ca) influenza vaccine (LAIV) is an effective tool for the control of influenza, most likely due to their ability to induce both humoral and cellular immune responses, easy application and relatively low manufacturing costs. Attenuated cold-adapted vaccine strains that have achieved a satisfactory balance between restricted replication and high immunogenicity are desirable. The immunogenicity of live attenuated vaccines may depend upon the interplay between its ability to induce pro-inflammatory cytokine responses and the relative sensitivity of the attenuated vaccine strain to an antiviral effect of these cytokines. To better understand the relationship between attenuation and induction of innate immunity as well as contribution of the early cytokine response to the relative immunogenicity of LAIVs, we have studied early protection induced by LAIV in vivo as well as early cytokine response in human cells macrophage origin in response to infection with vaccine strains or epidemic virus.

The aim of this study was to investigate the early immune response and protective activity in female CBA mice intranasally immunized with cold-adapted influenza vaccine strains of different genome compositions of 5:3 or 6:2. For experimental infection pandemic influenza viruses A/South Africa/3626/13 (H1N1)pdm09 and A/New York/61/15 (H1N1)pdm09 were used to be administered to animals at a dose of 106 EID50 at day 3 after immunization (challenge infection). Although challenge viruses replicate at mice lungs at various, extend, on day 10 after immunization mice were protected from death from 60 up to 80%. Reassortants LAIV did not differ statistically on these levels.

Study of the expression of IFN-α and IFN-β genes in human lung macrophage line cells THP-1 in vitro have shown that macrophages stimulated with vaccine strains with the genome formula 6:2 and 5:3, had a sufficient level of expression of these genes, comparable to that, as in infection with wild virus type A/South Africa/3626/13 (H1N1)pdm09. These data may indicate that surface proteins of influenza A virus are involved in the process of stimulation of the IFN-α and IFN-β genes.

Medical academic journal. 2019;19(3):37-46
Morphofunctional alterations of the hypothalamic neurons activity during sleep-wake cycle regulation disturbances after experimental traumatic brain injury
Gavrilov Y.V., Derevtsova K.Z., Korneva E.A.

Relevance. The study of sleep disorders mechanisms after traumatic brain injury is complicated and poorly understood. Traumatic damage to the structures that are responsible for the sleep-wake cycle regulation is a common cause of sleep disorders after traumatic brain injury. The number of hypothalamic neurotransmitter systems, which are involved in the sleep-wake cycle regulation, could change its functional activity after trauma that suggests their key role in the development of disturbances of this process.

The aim of the study was to assess the morphological alterations of the hypothalamus neurons that is involved in the regulation of sleep and wakefulness after traumatic brain injury in an experiment.

Methods. For a combined analysis of posttraumatic disturbances of the sleep-wake cycle and morphofunctional changes in the neurotransmitter systems which are involved in the regulation of the sleep-wake cycle, we used a polysomnography in rats during a month and then an immunohistochemical method for estimating the quantify the orexin A, melanin-concentrating hormone, histamine and tyrosine hydroxylase.

Results. The number of histamine-containing cells in the tuberomammillary nuclei of the hypothalamus is obviously decreased after traumatic brain injury in animals. This alteration of the degree of immunoreactivity of histamine-containing cells after traumatic brain injury correlated with sleep duration changes in animals. The number of noradrenergic and orexinergic neurons was compare with control animal group.

Conclusion. These results suggest that a change in the functional activity of histamine-containing neurons after traumatic brain injury may be the cause of post-traumatic sleep and wakefulness disorders. Our results may lead to a creating of a new approach for a therapy for posttraumatic sleep-wake disturbances.

Medical academic journal. 2019;19(3):47-56
Novel technologies
Lectin panel screening for evaluating of murine thymocytes apoptosis stages
Serebriakova M.K., Dotsenko A.A., Kudryavtsev I.V., Polevshchikov A.V.

The aim of the study was to investigate the interaction of lectins with various populations of maturing murine T-lymphocytes, as well as with thymocytes at different stages of apoptosis.

Materials and methods. Thymocyte typing of 80 CBA mice was performed by flow cytometry. The binding of lectins to cells in early and late apoptosis induced by the administration of hydrocortisone was also evaluated.

Results. The suitability of peanut and Helix pomatia lectins for differentiation of mature and immature mouse thymocytes has been established. 11 lectins bound to living cells, during the transition of cells to the state of early apoptosis, thymocytes were stained with 16 lectins, and upon transition to late apoptosis, 20 of 23 lectins bound to the cells.

Conclusion. The use of labeled lectins to assess the stage of murine thymocyte apoptosis does not have obvious advantages over existing methods. The degree of binding of all lectins to thymocytes in apoptosis increases as the charge on the membrane decreases and its permeability increases. For typing thymocytes in the early stages of maturation, peanut and Helix pomatia lectins can be used. Snowdrop and amaryllis lectins are not suitable for differentiation of thymocytes by maturity.

Medical academic journal. 2019;19(3):57-70
Approval of the method of electrophoretic separation and identification of some urine proteins in rats with toxic nephropathy
Sivak K.V., Zabrodskaya Y.A., Dobrovolskaya O.A.

The aim of the article. The aim was to test the method for determining certain protein markers in rat urine by electrophoretic separation followed by mass spectrometric identification for early diagnostic of nephrotoxicity. The objectives of the study included assessing the reproducibility of the protein separation method, comparing rats urine protein profiles normal and after gentamicin sulfate administration, as well as a biochemical and morphological study of kidney biopsy specimens.

Materials and methods. Gentamicin sulfate (GS) was administered intramuscularly to rats of both sexes at a dose of 60 mg/kg b.w. for consequence 5 days. Daily urine was collected in the background, on the 3rd, 7th and 14th day from the start of the administration of GS in the metabolic cages. We measured the concentrations of total protein and creatinine in urine samples, the level of lipids in the homogenates of the kidneys. Electrophoretic separation of urine proteins was performed in the Mini-PROTEAN Tetra Vertical Electrophoresis. The gels were stained, and the stained zones were excised and enzymatic hydrolysis of the proteins was performed. Spectra of tryptic peptides were recorded on an ultrafleXtreme MALDI-TOF/TOF mass spectrometer (Bruker, Germany). Proteins were identified in the Biotools program by accessing the Mascot database (matrixscience.com).

Results. Assessment of reproducibility of the results of electrophoretic separation of rat urine proteins showed an acceptable value of the coefficient of variation (on average 8.03%) and the error of analysis (Δanalysis = 14.53%). It that normally in rats of males the alpha-2-uroglobulin precursor dominates in urine and in females immunoglobulin G light chains dominate was show. Against the background of the administration of GS, leukocytes in pathological concentrations appear in the urine in rats of both sexes; in males, the proteomic profile has a strong intraspecific dispersion, including due to sperm contamination; in females, well identified zones of albumin, alpha-1-antitrypsin, aminopeptidase M, beta-2-microglobulin, and transferrin was appear. A biochemical study of kidney homogenates an increase in total cholesterol (males) and triacylglycerides (females) revealed. Pathomorphological changes were similar in male and female rats in the form of fatty degeneration of the proximal tubule nephrothelium and leukocyte infiltration of interstitium and confirmed changes in the spectrum of urine proteins.

Conclusion. Based on the analysis of the experimental results it was found that the use of the technology of electrophoretic separation of proteins in PAGE under denaturing conditions followed by MALDI mass spectrometric identification (PAGE-MALDI-TOF/TOF) and densitometric determination of the percentage of protein fractions is applicable for the detection of nephrotoxicity. Due to gender differences in the protein spectrum it is preferable to examine the urine of female rats. Pathomorphological changes did not have gender differences.

Medical academic journal. 2019;19(3):71-82
Clinical research
Lesions of brain structures in HIV infection
Trofimova T., Rassokhin V.V., Leonova O.N., Shelomov A.S., Yakovlev A.A., Azovtseva O., Bakulina E.G., Belyakov N.A.

A feature of the HIV epidemic is currently a large number of comorbid and severe forms of the disease, with frequent involvement in the pathological process of the brain. Brain lesions can be primary, caused by the human immunodeficiency virus itself and secondary, due to the development of opportunistic and secondary diseases and tumors. Correct and timely deciphering of the nature of brain damage is necessary for the choice of treatment tactics and as a consequence of reducing mortality.

Objective. To study the radiological manifestations of brain damage in HIV infection in urgent and planned admission of patients to specialized hospitals.

Materials and methods of research. In the work, studies were conducted to study the clinical and radiological manifestations of brain damage in HIV-infected patients admitted to various medical institutions with a diagnosis of HIV infection. Radiation examination of the brain was performed in adult HIV-infected patients (n = 410) using magnetic resonance imaging with intravenous contrast. The final diagnosis was made taking into account clinical, laboratory, radiological studies on the classification of ICD-10 in accordance with the domestic requirements of the formulation of comorbid diagnosis.

Conclusion. To correctly decipher the nature of brain damage, it is necessary to use comprehensive studies including clinical, laboratory and radiation examination methods. Magnetic resonance imaging with intravenous contrast is the method of choice in the examination of the brain in HIV-infected patients.

The structure of brain damage in HIV-infected patients had a different nature: in 54.4% there were signs of the presence of opportunistic and secondary diseases; in 24.9% — signs of HIV encephalopathy; in 13.2% — signs of nonspecific changes in small vessels of the brain, indicating premature aging or abnormal development; in 7.56% signs of involvement of the brain in the pathological process were not detected.

Structure and opportunistic secondary diseases were presented: toxoplasmosis of the brain — 18.3%; herpes lesions — 12.2%; chief of 10.24%; neuroinfection unspecified etiology is 12.2%; cryptococcosis — 4.39%; TB is 2.44%; lymphoma of the brain is 2.44%; MAC infection is 0.24%.

Brain damage in HIV-infected patients is largely characterized by synchronicity (mixed infection in 8.52 %) and multifactorial lesions.

Medical academic journal. 2019;19(3):83-95
History of medicine
Life and the “Scientific method” of Academician I.P. Pavlov (to 170th anniversary of the birthday)
Morgoshiia T.S.

The life and scientific work of I.P. Pavlov are presented. Little-known facts from the life of the scientist are covered. It is noted that the doctrine of higher nervous activity created by I.P. Pavlov is one of the greatest achievements of modern natural science. Outstanding properties and features of extremely rich human nature with amazing harmony are combined in one person, the like of which can hardly be found among other creators of experimental sciences. The laws discovered by him are related to the phenomena of mental life in animals and humans. Many researchers suffered a brutal setback while searching explanations to them. The works of Pavlov on the physiology of digestion was awarded the International Nobel Prize in 1904. It is considered that during 15–20 years of hard work Pavlov became the creator of an extensive branch of knowledge. The origins of the classical studies of the scientist on the physiology of digestion date back to his student years. From the first steps in science, he caught the main thread of interconnections of body systems and, regardless of the object of observation, studied the substance of the nervous systems. It is noted that the “scientific method of Pavlov” embodies the main features of his worldview, his views on the integrity of the organism and on the unity of the organism with the environment — views that make him related to the outstanding representatives of advanced materialistic biology and philosophy of the 19th and first half of the 20th century, primarily with Darwin, Sechenov, Timiryazev. It is emphasized that the “scientific method of Pavlov” in the new period of his creative work — in the process of studying the physiology of higher nervous activity — continuously improved, the importance of its components — analytical and synthetic approach in the study of complex functions of the body — more clearly emerged. Thus it is shown that the teaching of I.P. Pavlov played an outstanding role in the development of world medical science because in his experiments, he did not use template methods of scientific research, but used completely new, original and extremely simple ones, which gave convincing information and brought clarity to the most complex issues.

Medical academic journal. 2019;19(3):97-105

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