Activity of Parathyroid Hormone Receptor Genes in Ligamentum Flavum Biopsies of Patients with Spinal Canal and Dural Sac Stenosis at the Lumbar Level

Parathyroid hormone receptors PTH1R and PTH2R are poorly studied in the pathology of the vertebral column and may be involved in both ectopic ossification of the vertebral ligaments and fibrous growth of the extracellular matrix, as well as in other unknown processes occurring in the pathological focus. Aim. To study the expression of genes encoding parathyroid hormone receptors in intraoperative Ligamentum flavum samples of patients with stenosis of the spinal canal and the lumbar dural sac of the spine and to assess the correlation with the expression of other genes active in connective tissue in conditions of developing pathology.Materials and methods. Studies of the Ligamentum flavum were performed in 33 patients (17 women, 16 men) with stenotic processes of the spinal canal and dural sac of the lumbar spine. RNA was isolated from the biopsies using Qiagen reagents (Germany). Then reverse transcription was performed. cDNA was used for setting up a polymerase chain reaction (Promega Reagents, USA) using a CFX96 thermal cycler (Biorad, USA) with specially selected specific primers.Results. The expression of genes encoding parathyroid hormone receptors PTH1R and PTH2R was detected and evaluated for the first time in intraoperative Ligamentum flavum samples of patients with spinal canal and dural sac stenosis, and their relationship with the activity of genes encoding estradiol receptors (ESR1 and ESR2) and FGFR3 was revealed. For the first time, common features of PTH1R and PTH2R gene expression, as well as their differences, were revealed. It is proved that the intensity of expression of parathyroid hormone receptors in intraoperative Ligamentum flavum biopsies does not depend on age, gender, or the presence of bone and cartilage nodes according to MRI results. The interdependence of differential changes in the expression of genes of the receptor apparatus involved in the metabolism of Ligamentum flavum tissues was  revealed

Activity of genes of matrix metalloproteinases and their inhibitors in the Ligamentum flavum of patients with stenosing processes in spinal canal and dural sac

New data have been obtained for assessing the expression of genes of metalloproteinases and their tissue inhibitors (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2) in the Ligamentum flavum in patients with lumbar stenosis of spinal canal and dural sac. The features of the metabolism of the extracellular matrix (ECM) were revealed, the data obtained were compared with those for previously studied candidate genes. The search for relationships with the features of the ECM metabolic characteristics was carried out.The aim. To study the expression of genes of metalloproteinases and their tissue inhibitors in intraoperative biopsies of the Ligamentum flavum of patients with lumbar stenosis of the spinal canal and dural sac.Materials and methods. A group of 33 people (17 women, 16 men) with lumbar stenosis of the spinal canal and dural sac was studied; the average age is 45.73 ± 1.95 years. RNA was isolated from intraoperative biopsies of the Ligamentum flavum, reverse transcription was performed, and PCR using specific primers was performed.Results. In Ligamentum flavum of patients with stenosing processes of the spinal canal and dural sac, an increased activity of MMP-1 and insufficient response of TIMP-1 and TIMP-2 were found; the expression of MMP-1 increased synchronously with Dio2, and both genes decreased their activity with increasing age of the patient. In patients with Ligamentum flavum ossification, the MMR-8 gene was more actively expressed, and the synthesis of the mRNA of the MMR-9 gene decreased compared to the subgroup without ossification

Molecular Genetic Studies of Intraoperative Ligamentum Flavum Bioptates of Patients with Spinal Canal Stenosis

Background. Ligamentum flavum is involved in the development of stenosis of the spinal canal and dural sac, but the mechanisms underlying degenerative-dystrophic changes have not yet been sufficiently studied. Aim. To study the expression of candidate genes potentially involved in connective tissue metabolism in intraoperative samples of Ligamentum flavum of patients with stenosis processes of spinal canal and duralsac on the lumbar spine.Materials and methods. During the surgical treatment, Ligamentum flavum biopsies were collected from 33 people with stenosis processes of spinal canal and dural sac on the lumbar spine (16 men, 17 women). RNA was isolated, then reverse transcription was performed. After that, real time PCR was performed (CFX96, Biorad) with the specific primers (RealTimePrimers.com).Results. The characteristics of the expression of candidate genes that are active in the Ligamentum flavum of  the examined patient population are given: NAT1 and NAT2 acetyltransferase genes; genes that determine the intensity of local metabolism (Dio1, Dio2 and Dio3); estradiol receptor genes ESR1 and ESR2; genes encoding receptors for growth factors and parathyroid hormone. All Ligamentum flavum samples showed activity of the NAT, ESR 2, FGFR1, FGFR3, NA20, PTH1R, and PTH2R genes. In the vast majority of samples (93.9–97.0 %), the following genes were active: PDGFA, ESR1, CALCR, and PDGFB. In 21.2–39.4 % of samples, “silence” of the Dio1, Dio2, Dio3, NAT2 and GDF5 genes was detected, and only 39.4 % of samples revealed NAT1 transcripts. The highest heterogeneity of transcript content was observed for Dio1, NAT2, and Dio2. The most stable expression in Ligamentum flavum tissue and a narrow range of fluctuations were characterized by genes with a high level of activity AANAT, ESR2, NAA20 and genes with an average level of activity FGFR1, FGFR3, PTH1R and PTH2R.Conclusions. Ligamentum flavum is a promising little-studied substrate for molecular genetic research. The revealed features of gene expression provide new information about pathogenesis, and the new fundamental knowledge obtained can provide a basis for developing methods for preventing the development of epidural fibrosis

Climate and Transformation of Ecosystems by the Example of Natural Plague Foci of South-East of Russia

Shown was the influence of modern day warming and some other factors on natural plague foci of the European South-East of Russia. Analyzed were the basic mechanisms of transformation of biocenotic structure of natural foci complexes. It was shown that the tendency of gradual change of dominant carriers species would be preserved due to further warming of climate. As a result, the expansion of polyhostal natural foci of plague of semidesert type would be continued

Verification of Mathematical Models of Plague

Mathematic modeling and prognostication of infectious diseases epidemic process is a promising trend of epidemiologic investigations. The complex of mathematic models (SEIRF type) of plague epidemic process was developed for this purpose by the Russian Research Anti-Plague Institute “Microbe” and laboratory of epidemiologic cybernetics of N.F.Gamaleya Institute for Epidemiology and Microbiology. The data on the plague outbreak in 1945 in the rural settlement Avan’ (Aral region of Kzyl-Orda district of Kazakh SSR) were used to test working efficiency of this complex. The data analysis permitted to obtain the starting and boundary conditions for epidemic process modeling. In the process of modeling the mathematical models of epidemic process of plague with various ways of infection transmission for each epidemic focus in regard with historical data were used. The data were processed by the analytical platform Deductor 5.1. Identified was strong positive correlation between estimated and historical data – r = +0,71. The results received testify that mathematic models are effective and give high degree of confidence. They can be used to receive quantitative characteristics of prognosis for plague epidemic process development with different transmission routes considering that anti-epidemic measures have been taken

Hygiene of residentiai and public buildings

The purpose of the study is to study the favorableness of residential and public buildings.Цель исследования – изучить благоприятность жилых и общественных зданий

Change of the Shape of the Dural Sac in the Laminectomy Model at Different Stages of the Reparation in the Experiment

Epidural fibrosis is a dynamic pathological process that develops and progresses over time and is a polyetiological and multifactorial complication in the postoperative period during spinal surgery.Aim of the study. To study the reparative process and the formation of epidural fibrosis and its effect on the shape of the dural sac in the area of laminectomy at different periods of wound healing.Materials and methods. To assess the dynamics of the formation of epidural fibrosis and the involvement of the dura mater in this process, laminectomy was performed at the level of the LVI vertebra in 35 male Wistar rats at the age of 4–5 months. The animals were divided into 5 periods of withdrawal from the experiment on days 3, 7, 14, 21, and 28. The histological material was studied by staining with hematoxylin and eosin. To assess the deformation of the dural sac, the ratio of the diameter to the length of the canal was assessed on histological preparations in the laminectomy zone, and these measurements were carried out in a group of intact animals at the level of the LVI vertebra (n = 7). Results. During the observation process, a change in the ratio of the sizes of the dural sac has been observed. In the period from days 3 to 14, the anterior-posterior size of the dural sac progressively decreases, in parallel, the transverse size increases, which leads to a change in its shape. On follow-up, some form correction occurs. It is possible that the change in the shape of the dural sac in terms of up to 14 days is due to edema, plasma saturation of tissues, as well as the growth of connective tissue. The subsequent decrease in edema and the restructuring of the newly formed connective tissue leads to a correction of the shape of the dural sac.Conclusion. In the work, the dynamics of morphological changes in the zone of formation of epidural fibrosis during laminectomy in the experiment was assessed. The dynamics of changes in the lumen of the dural sac was established. The early involvement of the dura mater in the pathological process, its interest during the entire observation period was noted. Also, histological preparations show the involvement of the nerve fibers of the cauda equina in the pathological process from the early stages after surgery: vacuolization and destruction of nerve fibers, adhesion of fibers to each other and to the dura mater, as well as activation of endotheliocytes in the vasa nervorum

Factors of local conversion of iodothyronines correlate with indicators of hormonal, biochemical, and hematological profiles in patients with spinal canal and dural sac stenosis of the lumbar spine

In order to find out the mechanisms of pathogenesis of degenerative-dystrophic diseases of the spine, it is of particular interest to search for body parameters which are directly or indirectly interrelated with the key factors of peripheral conversion of nidus iodothyronines and constitute a system of network interactions, affecting metabolic indicators at the local and systemic level.The aim. To search for correlations of local key factors of peripheral conversion of Ligamentum flavum iodothyronines with indicators of biochemical, hematological and hormonal blood profiles of patients with stenosing processes of the spinal canal and dural sac in the lumbar spine.Materials and methods. 33 patients (15 males, 18 females) with stenosing processes of the spinal canal and dural sac in the lumbar spine were examined (mean age – 45.73 ± 1.95 years). The expression of deiodinase genes and other candidate genes was determined in Ligamentum flavum biopsies collected during surgical treatment. Biochemical, hematological and hormonal parameters were determined in peripheral blood. The resulting data array was processed in order to find correlations between the parameters of systemic and local metabolism.Results. The relationships of deiodinases with the expression of GDF5, MMP1, MMP3 and TIMP1 in Ligamentum flavum (p < 0.05) were found. Of the hormonal profile of the blood serum, the most significant indicators were thyreotropin, free triiodothyronine and thyroperoxidase antibodies. In the biochemical profile, levels of direct bilirubin, total cholesterol, HDL and LDL cholesterol and triglycerides changed along with the expression of deiodinases. Correlative relationships with the expression of deiodinases were found for the following hematological analytes of whole peripheral blood: hemoglobin, mean corpuscular hemoglobin concentration, numbers of granulocytes, lymphocytes, eosinophils, monocytes, band neutrophils, red cell distribution width and platelet crit. The data obtained indicate the involvement of peripheral conversion factors in the pathogenetic process and provide information to form a new view on the pathogenesis of degenerative-dystrophic processes in the Ligamentum flavum of patients with stenosing processes of the spinal canal and the dural sac in the lumbar spine

ФАЗОВЫЕ РАВНОВЕСИЯ В ЖИДКОМ МЕТАЛЛЕ СИСТЕМЫ Cu–Al–Cr–O

A thermodynamic analysis of phase equilibria in a Cu–Al–Cr–O system was performed. The study involved thermodynamic modeling of the liquidus surface of the Cu2O–Al2O3–Cr2O3 oxide phase diagram. To describe the thermodynamic activity of the molten oxide, an approximation of the sub-regular ionic solutions theory was used with the energy parameters determined in the modeling process. Melting characteristics of CuCrO2 were also evaluated during calculations. Calculation results were used to determine the coordinates of invariant equilibria points in the Cu2O–Al2O3–Cr2O3 ternary oxide system. The study also involved thermodynamic modeling of interactions in the Cu–Al–Cr–O system in the conditions of a copper-based metal melt. The temperature function of the reaction equilibrium constant was determined for the formation of solid CuCrO2 from the components of the Cu–Al–Cr–O molten metal system. The temperature function was obtained for the first order (Wagner’s) interaction parameter of Cr and O dissolved in liquid copper. The results of thermodynamic modeling for the Cu–Al–Cr–O system are represented as the surface of components solubility in metal, which allows us to relate the quantitative changes in the molten metal concentration to the qualitative changes in the composition of resulting reaction products. As a result of modeling, it was found that the given considerable concentrations of Al and Cr in the Cu–Al–Cr–O molten copper system form the |Al2O3, Cr2O3|ss solid solution particles as primary reaction products. The results of the study may be used to improve the chromium bronze smelting process.Проведен термодинамический анализ фазовых равновесий, реализующихся в системе Cu–Al–Cr–O. Выполнено термодинамическое моделирование поверхности ликвидус оксидной фазовой диаграммы Cu2O–Al2O3–Cr2O3. Для описания активностей оксидного расплава использовалось приближение теории субрегулярных ионных растворов, энергетические параметры которой были определены в процессе моделирования. В ходе расчета также оценены характеристики плавления соединения CuCrO2. По результатам выполненного расчета установлены координаты точек нонвариантных равновесий, реализующихся в трехкомпонентной оксидной системе Cu2O–Al2O3–Cr2O3. Также проведено термодинамическое моделирование процессов взаимодействия в системе Cu–Al–Cr–O в условиях существования металлического расплава на основе меди. Определена температурная зависимость для константы равновесия реакции, характеризующей образование твердого соединения CuCrO2 из компонентов металлического расплава системы Cu–Al–Cr–O. Получена температурная зависимость для параметра взаимодействия первого порядка (по Вагнеру) хрома и кислорода, растворенных в жидкой меди. Результаты термодинамического моделирования для системы Cu–Al–Cr–O представлены в виде поверхности растворимости компонентов в металле, которая позволяет связать количественные изменения в концентрации металлического расплава с качественными изменениями в составе образующихся продуктов взаимодействия. По результатам проведенного моделирования определено, что при значимых концентрациях алюминия и хрома в медном расплаве системы Cu–Al–Cr–O будут образовываться частицы твердого раствора |Al2O3, Cr2O3|тв.р в качестве основного продукта взаимодействия. Результаты работы могут быть интересны для совершенствования технологического процесса выплавки хромовых бронз

The effect of A-PRP-therapy on reparative regeneration of bone tissue with acute bone fractures of the limbs

Objective. To evaluate the effect of A-PRP-therapy on reparative bone regeneration in acute limb bone fractures. Material and Methods. The study consisted of two parts – in the first part we studied the effect of A-PRP-therapy on the model of a comminuted fracture created in the operating room, an experimental study conducted on 40 Mature rabbits of the Flander breed, all animals were divided according to the principle of analogues into 2 groups (20 animals): in the study group – on the 5th day after osteotomy, platelet-rich plasma was injected into the fracture area, in the comparison group – the fusion occurred without the influence of any drugs. The second part presents the results of clinical testing of A-PRP-therapy, analyzed the results of treatment of 16 women with low-energy fractures of the distal radius metaepiphysis. The study group consisted of 6 patients whose surgical treatment was supplemented by A-PRP-therapy on 7, 14 days after surgery. The control group consisted of 10 patients who underwent surgical treatment without A-PRP-therapy.Results. The use of platelet-rich plasma to stimulate reparative osteogenesis in accute fractures reduces the time of fracture consolidation by 9.5 ± 1.1%.Conclusion. Platelet-rich plasma (PRP) to stimulate reparative osteogenesis is an inexpensive, easy to perform and effective alternative to the methods considered. The possibilities of application of this technology in traumatology and orthopedics require further research in order to create protocols for the use of PRP-therapy to stimulate the maturation of bone calluses