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Translational Medicine

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Vol 7, No 5 (2020)
View or download the full issue PDF (Russian)
https://doi.org/10.18705/2311-4495-2020-7-5

CARDIOVASCULAR MEDICINE

6-16 1325
Abstract

Background. Atrial fibrillation (AF) is the most frequent arrhythmia. The method of catheter radiofrequency ablation (CRA) of pulmonary veins (PV) does not guarantee the preservation of sinus rhythm. Determination of predictors of AF relapses dictates the need in systemic approach taking into account demographic and clinical-instrumental characteristics of patients. Objective. Determination of preoperative predictors of AF recurrence within 3 year after follow-up CRA PV.

Design and methods. The study included 89 patients (50 men, 39 women; mean age 58 and 62 years respectively) followed during 3 years after CRA PV. The methods of principal components and discriminant analysis were used for analytical purposes. Results. The recurrence of AF was observed in 43 patients (48 %): during the first year — in 18 (43 %), during the second — in 16 (37 %), during the third — in 9 (20 %) cases. By consistently using the methods of descriptive and multivariant statistics a set of the preoperative indicators has been identified that distinguishes patients with AF relapses undergone CRA PV. It consists of the longivity of AF, the state of contractive myocardial function, the presence of ICD, cardioversion in the past and thyroid pathology. The contribution of modified risk factors: SBP level, BMI, tobacco smoking also are valued. Conclusion. Using of multivariant statistics allows to determine preoperative characteristics, which provide optimization of management of patients with AF.

17-28 656
Abstract

According to World Health Organization, annually cardiovascular diseases cause 17,5 billion deaths in the developed world. This is the reason why the study of molecular mechanisms of these pathologies has a huge importance for the development of new diagnostic and therapeutic strategies. One of the strategies on this matter is the research of the small extracellular vesicles or exosomes and its role in pathogenesis of cardiovascular diseases. Exploring their transporting and signaling functions in the development of acute coronary syndrome, stable angina, heart valve diseases, hypertrophic cardiomyopathy, vascular atherosclerosis has a great importance.

Exosomes are spherical vesicles of 30–100 nm, expressed by almost all human cells. Their cytoplasmic membrane has lipid bilayer structure with tetraspanins CD9, CD63, CD81 and CD82 as the markers. Exosomes act as effectors transferring microRNA, mRNA, cytokines and growth factors between varies cells.

The aim of this review is to analyze the literature data of exosomal role in the development of main cardiologic syndrome’s and evaluation of existed literature on exosomes potential as therapeutic target.

NEUROLOGY

29-42 977
Abstract
Background. To determine the optimal approach to managing patients in the acute period of stroke, the search for biomarkers that can increase value of existing diagnostic methods continues. Objective: to clarify the significance of the levels of neuron-specific enolase (NSE), glial fibrillar acid protein (GFAP), NR2-antibodies in the blood serum (BS) of patients in the acute period of ischemic stroke (IS) in dynamics, determine their relationship with the severity of neurological disturbances and short-term outcome. Design and methods. 40 patients were examined in the acute period of IS, mean age 72.6 ± 1.9 years. The levels of biomarkers were determined in the BS in the first 72 hours of IS and on days 10–14. Results. The concentration of NSE and GFAP in patients with IS in the first 72 hours exceeded the reference values and significantly decreased by 10–14 days (34.9 ± 5.9 → 17.7 ± 1.1; p = 0.007 and 0.4 ± 0, 1 → 0.2 ± 0.005, p = 0.22 respectively). The level of NR2 antibodies did not exceed of the reference values (1.01 ± 0.3), and in dynamics, by 10–14 days, an increase in the indicator was noted (1.1 ± 0.3), p = 0.007. In patients with more severe symptoms, the concentration of NSE, GFAP and NR2 antibodies was higher by 10–14 days. Patients who had an unfavorable short-term outcome by 10–14 days had a higher level of NSE, GFKB and NR2 antibodies. Conclusion. The investigated substances can be used as biomarkers in IS to control the degree of damage to the brain tissue, monitor the worsening of the pathological process, as well as for prognostic purposes.
43-52 723
Abstract
Background. Cerebral arteriovenous malformations (AVMs) are not static congenital lesions, but can grow, recur, and appear de novo after complete resection, embolization, or radiosurgery. Understanding the complex molecular biology of AVMs is critical to predicting their behavior during treatment and improving treatment outcomes. Objective. To study the dynamics of angiogenesis factors in the process of cerebral AVM embolization in order to develop a strategy for their personalized treatment. Design and methods. The study included 314 patients with AVM who received surgical treatment at the Department of Brain Vascular Surgery of the Polenov Neurosurgical Institute. Determined the level of vascular endothelial growth factor (VEGF), angiopoietin-2 (ANG-2) and matrix metalloproteinase-9 (MMP-9) in blood serum before and 24 hours after endovascular embolization using enzyme-linked immunosorbent assay (Personal Lab, Adaltis, Italy). Results. Primary patients (48.4 %) with AVM showed an increase in VEGF, MMP-9, ANG-2. A high level of VEGF and MMP-9 demonstrated AVM III grades according to Spetzler-Martin, AVM with a hemorrhagic flow type, with a deep drainage pattern, with afferents from the external carotid artery. The return to control values of all elevated growth factors after total embolization confirms the lack of potency for AVM recurrence. The absence of a decrease in aniogenesis factors after radical, according to angiographic criteria, embolization is a sign of subtotal AVM shutdown. Conclusion. A personalized concept of embolization in patients with a high risk of growth and recurrence has been formulated.

METABOLIC DISEASES

53-61 543
Abstract
Background. Congenital hyperinsulinism (CH) is characterized by persistent hypoglycemia, leading to irreversible damage to the cerebral cortex. The atypical form of CH (ACH) remains practically unexplored. Objective. Description of histological and immunohistochemical features of the pancreas in ACH. Design and methods. Material for research — fragments of the resected pancreas of 3 children with ACH aged 3, 6 and 7 months. Control group — pancreas of 9 children who died from heart malformations. Pancreatic tissue was stained with hematoxylin and eosin, an immunohistochemical reaction was performed with antibodies to chromogranin A, somatostatin, and transcription factors (TF) NeuroD1, Nkx2.2, and Isl1. Results. In all patients, numerous hyperplastic islets of Langerhans were observed, which in places merged with each other. In two patients, the lesion was limited to the pancreas area, and in one it covered the entire gland. All patients showed a sharp increase (p < 0.01) in the expression of NeuroD1 both in the exocrine and endocrine parts of the pancreas in the affected area: in 79.0 ± 23.4 % of endocrinocytes and in 88.0 ± 8.2 % of exocrinocytes (in the control 10.5 ± 7.9 % and 4.0 ± 4.9 % respectively). The expression of chromogranin A and TF Isl1 and Nkx2.2 increased statistically significantly (p < 0.01) only in affected endocrinocytes (chromogranin A — 62.3 ± 15.4 % of endocrinocytes, Isl1 — 82.0 ± 4.6 %, Nkx2.2 — 81.3 ± 4.6 %; in the control — 39.4 ± 7.9 %, 30.2 ± 16.2 % and 26.4 ± 11.9 % respectively). In 2 patients, there was a tendency to an increase in the number of somatostatin + endocrinocytes. Conclusion. ACH is morphologically very heterogeneous. Like other forms of CH, ACH was characterized by a statistically significant increase in the expression of chromogranin A and TF NeuroD1, Nkx2.2, Isl1, while the expression of somatostatin in general remained unchanged.
62-80 650
Abstract
Background. Kisspeptin system plays a fundamental role in the neuroendocrine control of hypothalamic-pituitary-gonadal axis, initiation of puberty and fertility. These observations suggest that kisspeptin system is a potential novel therapeutic and diagnostic approach for treating children with delayed puberty and hypogonadotropic hypogonadism and is currently a focus of translational research. Objective. Estimation of the functional activity of the kisspeptin system and its role in the genesis of delayed puberty. Design and methods. The experimental part of the study included 53 male Wistar rats. The clinical part of the study included 75 somatically healthy boys. The expression levels of kisspeptin receptors KISS1R in central androgen dependent tissues were evaluated by immunohistochemical method. Kisspeptin receptor levels and serum levels of kisspeptin were assessed by ELISA. Serum levels of luteinizing hormone and follicle-stimulating hormone were evaluated by chemiluminescent immunoassay. Results. A negative regulatory feedback was established between the concentration of kisspeptin and plasma testosterone both in the experimental and clinical parts of the study. Hypotestosteronemia leads to a significant decrease in the number of kisspeptin receptors in androgen-dependent tissues. Low testosterone levels cause degenerative-dystrophic changes in the neurons of the medial arcuate nucleus of the hypothalamus, which undergo partial regression during testosterone therapy. The level of kisspeptin significantly increases in individuals with delayed puberty. Serum kisspeptin levels exceeding 16.9 pg/ml is a reliable predictor of delayed puberty. Conclusion. Obtained results indicate the importance of translating them into clinical practice in order to substantiate novel diagnostic and therapeutic approach to the management of central forms of delayed puberty.

ЛУЧЕВАЯ ДИАГНОСТИКА И ТЕРАПИЯ

81-90 966
Abstract

Background. Currently, one of the topical issues of prenatal magnetic resonance imaging is accurate and timely diagnosis of pathological conditions of extrafetal structures of the fetus. In particular, the most acute problem is the need to improve the diagnostic accuracy of recognition and differentiation of placental adhesive-invasive pathology (PAIP). In the literature, there is no unified approach to the methodology and description of MRI examination of the placenta. Objective. To improve the diagnostic methods of the method of magnetic resonance imaging for the study of the placenta. Design and methods. A total of 293 MRI studies of the small pelvis of pregnant women aged 22 to 45 years (average — 35 years), in gestational age from 14 to 38 weeks (average 36 weeks) were performed and analyzed. Results. A clinical three-stage method of MRI of the placenta and an algorithm for systematized description of MRI of the placenta of pregnant women have been developed and implemented. Conclusion. The developed systematic approach to the study of the placenta will help improve the capabilities of the MRI method for examining the placenta in connection with the demand for accurate and correct interpretation of this organ in vivo.

HISTORY OF MEDICINE

91-108 1611
Abstract
Today, robot-assisted surgery and the use of robots in medicine marks a qualitatively new stage in the development of minimally invasive technologies and endovideosurgery, due to the high level of accuracy, functionality and ergonomics of modern robotic systems. With the help of robotic technologies, the quality of diagnostic manipulations as well as the results of therapeutic procedures and surgical interventions are significantly improved, which ultimately leads to an improved prognosis and quality of life for patients, while also expanding the capabilities of clinicians. This review article presents the main historical milestones and prerequisites for the development of automation and robotic technologies used in various industries, from ancient times to the present. The history of the use of robotic procedures in various fields of medicine is briefly described. Special attention is paid to robot-assisted surgery as one of the main bases for applying modern technologies. At the moment, we can safely say that medical robotics plays a very important role in the development of surgery of the future.

Experimental studies

109-118 479
Abstract

Background. In preschool age, age-related changes in the principles of information processing are observed. The formation of concepts is a convenient approach for the comparative study of the cognitive abilities of healthy children and children with a high risk of the impairment of the intelligence formation. Objective. The goal of the work was to conduct the comparative study of the formation of concepts using real geometric figures and flat contour images as stimuli in 4–5-year-old children. Design and methods. The original method was used in which a child independently revealed a certain pattern of choosing stimuli under the conditions of the simultaneous presentation of four objects or images. Results. The speed of forming the concepts of the "size" and "shape"/"contour shape" did not significantly differ in the 4-5-year-old children. However, the formation of both the concepts required the longer learning period with using the contour images compared to the the learning period with using real objects as stimuli. The heterogeneity of the 4–5-year-old children group was related to the difference of the speed of forming concepts. This fact implies the qualitative differences in the processing of information. In the children with long-lasting training, the synthesis of separate empirical representations took place due to the inductive function of abstract thinking. Some children probably have already possessed those concepts and they could quickly relate rewarded concrete stimuli to those concepts using the deductive function of abstract thinking. Conclusion. Our experimental psychological method using contour images can be used in clinical practice with the subsequent transition to stimuli on a computer screen with the simultaneous recording of brain activity to study the dynamics of the children mental development, as well as to identify delays and deviations in their cognitive sphere.

119-130 1291
Abstract
Background. The study of red bone marrow in preclinical studies is an important component of the study program of the drug. Objective. To compare the results obtained in parallel studies of the material from the same animal by two different methods for rats, rabbits and mice (cytological examination of the material obtained from the femur and histological examination of the material obtained from the sternum). Design and methods. Bone marrow obtained from intact animals was studied. Cytological preparation was stained according to Romanowski–Giemsa, histological preparation was prepared in the usual way and stained with hematoxylin-eosin. Stained preparations were examined by microscope. Results. As a result of this study was sets of myelograms with leuko-erythroblast ratio and neutrophil maturation index. Conclusion. A number of conclusions were made: when conducting preclinical studies, the most appropriate can be considered a bone marrow sampling from the femur; the fence can be carried out both for cytological examination, and for histological; taking into account the high variability of indicators in preclinical studies of myelograms, it is necessary to have control groups of (intact) animals of the same species that did not receive the study drug; Myelograms in rabbits turned out to be the least varied, both according to the results of our own studies (with histological and cytological studies), and when compared with literature data, which allows us to recognize rabbits as the best object for studying the composition and function of red bone marrow; when comparing the literature data, significant patterns in the number of cells at different age periods were not observed in the studied animal species, and, therefore, in preclinical studies using KKM analysis, animals of any age can be used.


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ISSN 2311-4495 (Print)
ISSN 2410-5155 (Online)