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Siberian Scientific Medical Journal

2020 year, number 6

1.
Possibility of using the infrapatellar (Hoffa’s) fat pad as a source of autologous stem cells

Anastasia V. Korel1, Irina I. Kim2, Elena L. Strokova1, Natalia Yu. Pakhomova1, Arkady F. Gusev1, Alla M. Zaydman1
1Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Novosibirsk, Russia
akorel@niito.ru
2Research Institute of Clinical and Experimental Lymphology - Branch of Federal Research Center Institute of Cytology and Genetics of SB RAS, Novosibirsk, Russia
kii5@yandex.ru
Keywords: infrapatellar (Hoffa’s) fat pad, adipose tissue, CD markers, differentiation, mesenchymal stem cells

Abstract >>
Stem cells are the basis for the creation of tissue-engineered structures in regenerative medicine. The most well-studied sources of stem cells are the embryo and bone marrow. The use of embryonic cells is associated with ethical problems, and the collection of bone marrow is accompanied by invasive procedures. Using adipose tissue as a source of stem cells avoids these problems. But the collection of adipose tissue requires additional interventions, which does not exclude the occurrence of cosmetic defects. Aim of the study was to investigate the possibility of using mesenchymal stem cells (MSCs) isolated from the infrapatellar (Hoffa’s) fat pad. Material and methods. As a source of MSCs, tissue samples of Hoffa’s fat pad removed during the operation were used (8 cases), as a control - MSCs isolated from human adipose tissue (6 cases). MSCs were isolated using an enzymatic method. At the 3rd passage, phenotyping with specific antibodies against CD34, CD45, CD73, CD90, CD105 was performed by flow cytometry. Differentiation in the chondro- and osteogenic direction was carried out at the 3rd passage with the appropriate differentiation media. Chondrogenic differentiation was confirmed by staining with alcian blue, osteogenic - staining according to von Kossa. Results and discussion. Statistically significant decrease in CD105 expression, increase in CD73, CD34 expression and lack of adequate differentiation under standard conditions of differentiation media by MSCs isolated from the Hoffa’s fat pad compared to control was found. The data obtained indicate a discrepancy between the cells isolated from the Hoffa’s fat pad and the requirements for MSCs. Conclusion. The infrapatellar (Hoffa’s) fat pad cannot be used as a source of standardized MSCs.



2.
Effectiveness and safety of lidocaine use (review)

Aleksandr V. Matveev1,2, Anatoliy Ye. Krasheninnikov3, Elena A. Egorova4, Elena A. Matveeva4
1National Scientific Center of Pharmacovigilance, Moscow, Russia
avmcsmu@gmail.com
2Medical Academy n.a. S.I. Georgievsky, Crimean Federal University n.a. V.I. Vernadsky
3National Scientific Center of Pharmacovigilance, Moscow, Russia
anatoly.krasheninnikov@drugsafety.ru
4Medical Academy n.a. S.I. Georgievsky - Crimean Federal University n.a. V.I. Vernadsky, Simferopol, Russia
elena212007@rambler.ru
Keywords: ventricular arrhythmias, ventricular fibrillation, lidocaine, antiarrhythmic drugs

Abstract >>
Cardiac arrhythmias are complications of many cardiovascular diseases. They quite often acquire an unpredictable course and can result in the death. According to epidemiology data, heart rhythm disorders lead to the sudden death of about 200 thousand people in the Russian Federation annually. Sudden cardiac death overtakes about 400 thousand outpatients and hospital patients in the USA and about 280 thousand patients in Europe. The unpredictability of the occurrence and the transience of cardiac arrhythmias require urgent measures, including both non-pharmacological (electrical pacing, electrical shock therapy) and pharmacotherapeutic methods of treatment. This review is devoted to the study of the clinical features of the lidocaine infusions in patients with ventricular arrhythmias caused by an increase of the conducting cardiomyocytes automatism. The article presents the results of comparative effectiveness and safety studies of lidocaine prescribed for the treatment of ventricular tachycardia and ventricular fibrillation (in the absence of the effect of electro-impulse therapy). Lidocaine is compared with other antiarrhythmic drugs such as amiodarone, sotalol, bretylium tosylate and procainamide. Recommendations of ILCOR (International Committee for Interaction in the Field of Resuscitation), AHA (American Cardiology Association), ECS (European Cardiology Society) and European Society for Resuscitation for the treatment of refractory forms of ventricular arrhythmias and ventricular fibrillation are also discussed.



3.
Development of invasive EEG in epilepsy surgery (review)

Vidzhai M. Dzhafarov, Jamil A. Rzaev
Novosibirsk Center of Neurosurgery of Minzdrav of Russia, Novosibirsk, Russia
mvijayd@hotmail.com
Keywords: epilepsy, EEG, invasive video-EEG monitoring, stereo-EEG, subdural EEG monitoring

Abstract >>
There are different diagnostic methods that used for localization of the seizure onset zone in focal refractory epilepsy cases. Invasive video-EEG recording is the «gold standard» in determining the epileptogenic zone among other diagnostic methods. Invasive EEG already has a long history of using. This article provides historical review and analysis of the techniques, their advantages and disadvantages, current issues.



4.
Dopaminergic system and its relationship with the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid systems (review)

Irina N. Molodovskaya
N. Laverov Federal Center for Integrated Arctic Research of UrO RAS, Arkhangelsk, Russia
pushistiy-86@mail.ru
Keywords: dopamine, dopaminergic system, sex hormones, thyroid hormones

Abstract >>
This article reviews literature data on the activity of the central and peripheral dopaminergic systems, as well as its relationship with the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-thyroid systems. Studies have shown that dopamine levels vary depending on the territory of residence, while the data on the age dynamics of the plasma dopamine level contradict each other, which does not allow an unambiguous conclusion about a decrease or increase in its level with age. Most studies focus on the functions of dopamine in the central nervous system. Symptoms of several brain diseases, including schizophrenia, Parkinson’s disease, attention deficit and hyperactivity disorders and depression, are alleviated by the pharmacological modulation of dopamine transmission. However, there is evidence of a functional role of peripheral dopamine. While dopamine of the central dopaminergic system inhibits the secretion of thyrotropin, dopamine synthesized by sympathoadrenal nerve cells, heparinocytes, and thyroid parafollicular cells on the periphery stimulates the formation and release of iodothyronines. The neuroprotective effects of sex steroids determine the prevalence of studies of their role in preservation and maintaining the activity of the dopaminergic system. The dopaminergic system also affects the levels of sex hormones, enhancing aromatase activity, inhibiting the synthesis or secretion of prolactin, regulating the levels of gonadotropins and steroidogenesis in Leydig cells. The peripheral and central dopamine systems are sensitive to environmental influences, which indicate the relationship between the peripheral and central links.



5.
Pulmonary valve: contradictions in terminology and anatomy

Andrei A. Iakimov1,2
1Ural State Medical University of Minzdrav of Russia, Yekaterinburg, Russia
ayakimov07@mail.ru
2Ural Federal University n.a. the First President of Russia B.N. Yeltsin
Keywords: gross anatomy, anatomical terminology, heart anatomy, heart valves, pulmonary valve, pulmonary artery

Abstract >>
Data on the anatomy of human heart valves is of a great importance for cardiac surgery, X-ray and ultrasound diagnostics, and additive technologies in bioengineering. This review analyzed Russian and English-written papers and presented contradictions of terminology, macroscopic and microscopic structure, topography of the normal pulmonary valve. The article compared such terms as «pulmonary valve» and «pulmonary root», the approaches of different scientific sources for naming the sinuses and leaflets and analyzed constituents of the pulmonary valve complex. Pulmonary root appeared us to be a distinct structure that includes the distal part of right ventricular outlet and proximal part of the pulmonary trunk. Interleaflet triangles and valvular commissures as well as semilunar leaflets and sinuses of Valsalva are thought to be parts of pulmonary valve complex. According to modern concepts, interleaflet triangles and valvular commissures are not the same and should be distinguished. The mouth of the pulmonary root is not surrounded with planar fibrous ring which anybody could reveal by dissection or histology technics, so the “fibrous ring” of the pulmonary artery is nothing more than an anatomical myth. The paper cited morphometrical data on the perimeter, valve diameters, sizes of semilunar leaflets and sinuses, revealed various models of regression and correlation between the size of the valve and body parameters. We summarized data on cell and fiber architectonics of the valve. Terminological and morphometric consensus in heart valves anatomy is the mandatory step on the way to the evidence-based morphology.



6.
Effect of new water-soluble phenolic antioxidants on the activity of Nrf2-driven enzymes, glutathione system, and Nrf2 translocation into the nucleus

Elena B. Menshchikova1, Nikolay K. Zenkov1, Peter M. Kozhin1, Anton V. Chechushkov1, Vladislav S. Pavlov1, Lidia P. Romakh1, Marina V. Khrapova1, Anastasia E. Serykh1, Oksana B. Gritsyk1, Natalya V. Kandalintseva2
1Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia
lemen@centercem.ru
2Novosibirsk State Pedagogical University, Novosibirsk, Russia
aquaphenol@mail.ru
Keywords: reactive oxygen and nitrogen species, antioxidants, Keap1/Nrf2/ARE signaling system, NAD(P)H:quinone oxidoreductase 1, glutathione S-transferase, glutathione peroxidase, glutathione reductase, glutathione system

Abstract >>
Understanding the role of reactive oxygen and nitrogen species in eustress (redox balance) and distress (oxidative stress) development poses new challenges for biomedical scientists and pharmacologists in the search for compounds that can not only have a direct antioxidant (antiradical) effect, but also affect redox-sensitive signaling pathways, primarily Keap1/Nrf2/ARE system. Aim of the study was to investigate the influence of novel water-soluble structurally related monophenols on key elements of Keap1/Nrf2/ARE system induction (activity of Nrf2-driven enzymes, the state of the glutathione system, and intracellular redistribution of transcription factor Nrf2). Material and methods. Five original hydrophilic structurally related monophenols, differing in the number of tert-butyl ortho-substituents, the length of the para-alkyl substituent, and the presence of a divalent sulfur or selenium atom in it were investigated (phenoxane, the potassium salt of phenosan acid, was used as a reference compound). Cell lines U937 and J774 were cultured for 24 h in the presence of tested compounds, and comparative analysis was performed of its ability to induce the synthesis of Nrf2-driven enzymes of phase II xenobiotic detoxification pathway and antioxidant enzymes (NAD(P)H: quinone oxidoreductase 1 (NQO1), glutathione S-transferases (GST), glutathione peroxidases, glutathione reductase (biochemical spectrophotometric methods were used to study their activity), as well as to influence the state of glutathione system (spectrophotometry) and translocation of transcription factor Nrf2 into the nucleus (immunofluorescent staining, confocal microscopy) (key events of Keap1/Nrf2/ARE signaling system activation). Results and discussion. Monophenol TS-13 have found to be the most effective inducer of tested enzymes in U937 cells among the structural analogs, while the structure of the para-alkyl substituent and the degree of OH group hindrance are important for the implementation of this effect; TS-13 also effectively enhanced Nrf2 import into J774 cell nucleus. The NQO1- and GST-inducing abilities of structurally related monophenols are closely interrelated, which indicates the possibility of coordinated induction of these enzymes and the presence of a common regulatory system that ensures their activation in response to cell treatment with phenolic antioxidants.



7.
Toxic effect of copper-zinc pyrite ore on erythropoiesis in chronic experiment

Klara R. Ziyakaeva, Aliya F. Kayumova
Bashkir State Medical University of Minzdrav of Russia, Ufa, Russia
klazia@yandex.ru
Keywords: erythropoiesis, erythroblastic islet, red blood cells, heavy metals

Abstract >>
Natural ores contain a large number of harmful components for human health. Workers of mining and processing enterprises, who have long-term contact with these natural elements, are often diagnosed with anemia, that pathogenesis is not sufficiently studied. Aim of the study was to detail the mechanisms of rats’ erythron disorders in the long-term intoxication by natural complex of heavy metal compounds of copper-zinc pyrite ore. Material and methods. The work was performed on 60 white non-linear male rats aged 3-4 months weighing 220,52 ± 15,51 g. The experimental group of animals ( n = 40) were injected orally with water suspension of copper-zinc powder in a bread crumb an hour before standard feeding during 75-120 days. The blood and bone marrow of experimental groups of rats were carried out on the 75-th, 90-th, 105-th and 120-th days of the experiment. The blood and bone marrow of rats’ control groups were studied on the 75-th and 105-th day. The central part of erythron was assessed by the number and composition of the erythroblastic islets (EI) of bone marrow, the number of free macrophages, the coefficients of involvement of colony-forming units of red blood cells (CFU-E) and macrophages into erythropoiesis. Results. In the peripheral blood of experimental rats the number of red blood cells and the content of hemoglobin were reliably less than the control values on the 90-th and 120-th day, the number of reticulocytes was exceeded the control group on the 75-th, 105-th and 120-th day. In the bone marrow of experimental rats there were only a single EI1 and EI2 classes of maturity. Throughout the experiment, the content of free macrophages and EI with reticulocytes «crown» in the bone marrow of rats was elevated, and the concentration of iron and erythropoietin in the blood, on the contrary, was reduced. The intensity of CFU-E involvement in the erythropoiesis was less than the control level by 2 times on 105th and 120th days of the experiment. Conclusion. With long-term introduction of copper-zinc pyrite ore in the bone marrow of rats the process of formation of EI de novo is suppressed by destabilizing the contact of free bone macrophages with young red blood cells. There is reduces in the content of serum erythropoietin and bound iron, that combines with the change of erythropoiesis nature, leads to decreasing of the number of mature red blood cells and content of hemoglobin in the peripheral blood.



8.
Some morphological factors of resistance of the bronchial wall to the development of chronic obstructive lung disease in smoking individuals

Elena A. Gereng, Irina V. Suhodolo, Raisa I. Pleshko, Ekaterina B. Bukreeva, Anna À. Bulanova, Ivan S. Kremis, Tatyana S. Klyushina
Siberian State Medical University of Minzdrav of Russia, Tomsk, Russia
e-gereng@mail.ru
Keywords: chronic obstructive pulmonary disease, bronchial biopsy, bronchial vascular remodeling

Abstract >>
According to current epidemiological studies, chronic obstructive pulmonary disease (COPD) develops in only 15-20 % of smokers. This suggests that exposure to tobacco smoke is just a trigger of the pathological process, and other pathophysiological factors play a key role in the development of COPD. The aim of the study was to perform morphological analysis of bronchial mucosa features in smokers with and without chronic obstructive pulmonary disease. Material and research methods. Morphological and electron-microscopic analysis of biopsy samples of the bronchial mucosa of smoking patients with ( n = 40) and without ( n = 30) chronic obstructive pulmonary disease was carried out. Òhe study involved men (80.2 % of men) and women aged 42 to 67 years (62.3 ± 2.24 years) with smoking experience of more than 20 years and smoking intensity of 20-45 pack-years. In the main group was a verified diagnosis of COPD. All patients of the studied groups underwent morphological, morphometric counting of bulk densities of various types of epithelial cells and structures of their lamina propria of the bronchial mucosa, as well as the density of inflammatory infiltrate and various cell populations, immunohistochemical (typing of CD4- and CD8-positive lymphocytes, expression of transforming growth factor β1 receptors) and electron microscopic analysis of bronchobioptates. Results and discussion. Smokers without chronic obstructive pulmonary disease develop exudative inflammation, which does not violate the structural architectonics of the epithelial layer, but causes activation of protein-synthetic and energy processes in the epithelial cells of the bronchial wall. With prolonged exposure to tobacco smoke associated with the development of chronic obstructive pulmonary disease, chronic neutrophilic inflammation forms in the bronchial mucosa, leading to a violation of the functional morphology of the vessels and epithelial cells of the bronchial mucosa, followed by remodeling of the bronchial wall.



9.
The role of hematological parameters as predictors of mortality in elderly patients in the hospital period

Lyudmila V. Borisova1,2, Svetlana A. Rukavishnikova3,4, Alexander S. Pushkin5,6,7, Timur A. Akhmedov3,4, Vladimir V. Yakovlev8
1Saint-Petersburg Institute of Bioregulation and Gerontology, Saint-Petersburg, Russia
lucibor@yandex.ru
2City multidisciplinary hospital ¹ 2
3City multidisciplinary hospital ¹ 2, Saint-Petersburg, Russia
kdlb2@yandex.ru
4First Pavlov State Medical University of St. Petersburg of Minzdrav of Russia
timaxm@gmail.ru
5Saint-Petersburg Institute of Bioregulation and Gerontology, Saint-Petersburg, Russia
pushkindoc@mail.ru
6City multidisciplinary hospital ¹ 2
7First Pavlov State Medical University of St. Petersburg of Minzdrav of Russia
8Military medical Academy of S.M. Kirov, Saint-Petersburg, Russia
yakovlev-mma@yandex.ru
Keywords: acute coronary syndrome, hematological parameters, predictors, elderly and senile age

Abstract >>
The development of algorithms for predicting adverse outcomes, including death in elderly and senile patients, is an urgent issue. Potential predictors include hematologic parameters. A clinical blood test is one of the most affordable diagnostic methods in practical medicine, reflecting systemic pathological processes in the human body based on a quantitative assessment of the cellular composition and blood morphology. The aim of this study was to evaluate hematological parameters as predictors of in-hospital mortality in patients of the elderly and senile age with acute coronary syndrome. Material and methods. The study included 277 patients with acute coronary syndrome. The study of hematological parameters was carried out on a CELL-DYN Sapphire hematology analyzer (Abbott Laboratories, USA). The values of neutrophil-lymphocytes ratio and platelet-lymphocytes ratio were also evaluated as predictors of in-hospital mortality. Results. High content of leukocytes (above 10.45 × 109/l) during hospitalization in patients with ACS aged 60-74 years are associated with a higher risk of death at the hospital stage. Among patients with ACS aged 75-89 years, the risk of death is associated with the following changes in peripheral blood upon admission: a decrease in the absolute number of eosinophils below 0.086 × 109/l, an increase in the absolute number of basophils above 0.079 × 109/l and a decrease in platelet-lymphocytes ratio below 31.06.



10.
Risk factors in patients with non-alcoholic fatty liver disease associated with arterial hypertension, overweight and obesity

Yuri A. Nikolaev, Evgenia V. Sevostyanova, Vladimir Ya. Polyakov, Igor M. Mitrofanov, Alina A. Us
Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Russia
nicol@centercem.ru
Keywords: non-alcoholic fatty liver disease, arterial hypertension, overweight, obesity, risk factors

Abstract >>
Purpose of the study was to investigate the features of the occurrence of risk factors in patients with non-alcoholic fatty liver disease associated with arterial hypertension, overweight and obesity. Material and methods. The object of the study was the data of 14 393 case histories of patients with arterial hypertension (AH), non-alcoholic fatty liver disease (NFLD), overweight body (OB) and obesity, examined and treated at the clinic of the Federal Research Center for Fundamental and Translational Medicine (Novosibirsk). Results and discussion. Features of biochemical parameters in patients with NFLD with AH, OB and obesity were studied in comparison with patients with isolated diseases. It was shown that in patients, in case of the presence of this comorbidity, the value of transsystem polymorbidity is statistically significantly increased compared with groups of patients with isolated diseases. It was established that patients with concomitant diseases have higher, statistically significant values of systolic and diastolic blood pressure, body mass index. They have higher concentrations of total cholesterol, triglycerides, high density lipoprotein cholesterol, glucose, uric acid in the blood serum, higher atherogenic index. A study of the frequency of occurrence of risk factors in the groups showed the highest frequency values in patients with associated diseases: high blood pressure, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, hypoalphacholesterolemia, hyperlipidemia, increased atherogenic index, hyperglycemia, hyperuricemia, the higher levels of C-reactive protein, which indicates that with associated pathology, changes in carbohydrate, lipid and purine metabolism are more pronounced. These changes are factors that aggravate the course of the pathology and are risk factors for the development of diabetes mellitus, atherosclerosis and associated conditions, which requires a personalized approach to the treatment and prevention of this category of patients. The results of this study can form the basis for the development of new medical technology for assessing the severity of condition in patients with non-alcoholic fatty liver disease combined with arterial hypertension, overweight and obesity.