Connective Tissue Metabolism Research Articles

THE INFLUENCE OF THE CULTURE OF FIBROBLASTIC CELL ELEMENTS ON THE INDICATORS OF THE METABOLISM OF CONNECTIVE TISSUE IN EXPERIMENTAL ANIMALS

The number of patients with degenerative tendon disease affects millions of people both among athletes and the general population, causing significant socio-economic consequences. Despite the availability of various methods of conservative and surgical treatment, more than a third of patients experience constant pain. Objective. To study the indicators of the metabolism of connective tissue in animals with a model of degenerative damage to tendons against the background of the introduction of a culture of fibroblastic cell elements. Methods. Therefore, the development of methods for restoring the structure of tendons using cell cultures, in particular fibroblasts, will allow to optimize the course of reparative processes, reduce the risk of complications during surgical intervention and accelerate healing, and at the molecular level — to improve the structure of collagen fibers. Laboratory studies of biochemical markers of a tendon with a degenerative-dystrophic lesion and against the background of the introduction of cell culture can help in the differential diagnosis of its extracellular matrix. Results. The experimental data obtained by us indicate the presence of differences in the biochemical markers of tendons with degenerative-dystrophic lesions in rats 7, 21, and 45 days after the introduction of culture of fibroblastic cell elements. However, 45 days after the introduction of the culture of fibroblast cell elements, the normalization of metabolic processes in the extracellular matrix of connective tissue occurs, namely, the activity of collagenase and the concentration of protein-bound hydroxyproline approaches normal values. This indicates the predominance of the synthetic phase over the catabolic one in collagen metabolism. Conclusions. In this context, the introduction of culture of fibroblastic cell elements, as an alternative anti-inflammatory method, may provide another potential opportunity in the treatment of chronic degenerative-dystrophic lesions of the Achilles tendon.

Genetic Polymorphisms of COL1A1 Promoter Region (rs1800012) and TGFB1Signal Peptide (rs1800471): Role in Cervical Insufficiency Susceptibility?

A structural or functional cervix problem prevents a woman from carrying a full-term pregnancy, which leads to the disease known as cervical insufficiency. Cervical insufficiency is partially inherited, and in certain situations, variations in genes related to connective tissue metabolism may be involved. The main objective of this investigation was to describe the collagen type I alpha 1 chain (COL1A1) gene rs1800012 polymorphism and the transforming growth factor beta 1 (TGFB1) gene rs1800471 polymorphism in a cohort of patients suffering from cervical insufficiency. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays have been used to analyze the DNAs of 93 patients with cervical insufficiency and 103 healthy controls. The chi-square test was used for statistical analysis. There were significant differences in the genotype frequencies of the COL1A1 gene rs1800012 (G > T) and TGFB1 gene rs1800471 (G > C) polymorphisms between the patient and the control groups (p = 0.049 and p = 0.049, respectively). Also, the C allele of the TGFB1 rs1800471 polymorphism was significantly higher in the patient group than the control group (p = 0.016). Following clinical assessment, the COL1A1 rs1800012 polymorphism was found to be connected to the history of cerclage (p = 0.010). Additionally, the frequency of the TT/GG composite genotype of COL1A1 rs1800012/TGFB1 rs1800471 polymorphisms was significantly lower in the patient group than the control group (p = 0.049). The TT genotype of COL1A1 rs1800012 polymorphism was found to be protective against cervical insufficiency, while the C allele of TGFB1 rs1800471 polymorphism was found to predispose to the disease. It appears that the TT/GG composite genotype of COL1A1 rs1800012/TGFB1 rs1800471 polymorphisms protects against cervical insufficiency.

FEATURES OF THE COURSE OF GESTATION IN WOMEN WITH MITRAL VALVE PROLAPSE AGAINST THE BACKGROUND OF UNDIFFERENTIATED CONNECTIVE TISSUE DYSPLASIA

The article is devoted to the problems associated with connective tissue dysplasia (CTD), predominantly undifferentiated forms of the disease (nDST). The topic's relevance is due to the high prevalence of this pathological condition. The generalized nature of connective tissue damage with the involvement of the reproductive system in the pathological process significantly affects the course of pregnancy and Birth. Complications that may be associated with pregnancy, childbirth, and the postpartum period in women with nDST and which cause a high need for surgical aids: amnio-, episio- and perineotomy, and cesarean section are presented. Particular attention is paid to magnesium, which plays one of the determining roles in the complex biosynthesis of the extracellular matrix in the formation of connective tissue and the morphofunctional state of fibroblasts. The methods used to detect connective tissue metabolism disorders (determination of the level of oxyproline and fibronectin in blood serum, pyrinx D and glucosaminoglycans in urine, etc.) are described. Given the lack of reliable diagnostic (biochemical and genetic) criteria for nDST, special attention is paid to the need for an integrated approach to assessing the condition of patients using anamnesis data, the results of clinical, instrumental, and laboratory examinations.

ВЛИЯНИЕ ОБЩЕСОМАТИЧЕСКИХ ФАКТОРОВ В РАЗВИТИИ ОСЛОЖНЕНННОЙ КАТАРАКТЫ И ГЛАУКОМЫ НА ФОНЕ ПСЕВДОЭКСФОЛИАТИВНОГО СИНДРОМА (ОБЗОР ЛИТЕРАТУРЫ).

The variety of surgical methods, modified approaches, and modern advances make it possible to predict the outcome of the intraoperative course in cataract and glaucoma surgery with minimal risk of complications. Interest in pseudoexfoliation syndrome will not subside and research and observations will be carried out at a broad clinical level, as the trend towards increasing life expectancy in the middle and older population continues. Pseudoexfoliation syndrome is a complex multifactorial process that is associated with cataracts and glaucoma. The etiology of PES remains unclear, despite the modern approach, the centuries-long development of clinical ophthalmology, non-nophysiology, and molecular biology. However, later, scientists, having discovered deposited abnormal material in internal organs and tissues, came to the conclusion that this syndrome is a systemic disorder of connective tissue metabolism. According to some authors, factors contributing to the development of this syndrome may be bad habits (smoking for many years), chronic somatic pathologies, mainly cardiovascular diseases, endocrinological pathologies, hypertension, atherosclerotic deposits, vascular aneurysms. Other authors have studied the risk of developing glaucoma with comorbid pathologies, noting the high incidence of cardiac and cerebrovascular pathologies. Comorbid pathologies can often increase intraocular fluid, which in turn can provoke the development of transient hypertension. The authors, comparing pseudoexfoliation syndrome with primary open-angle glaucoma, noted the influence of somatic conditions on orbital blood flow, which can also disrupt the hydrodynamics of the eye in the long term. In glaucoma and cataract surgery, there are various surgical, drug and non-drug approaches to improve the condition of the visual organ. This review describes the developments of various technologies, modified approaches, and the development of surgical instruments to solve complex problems for the surgeon.

Search for molecular markers of joint hypermobility

Background: Joint hypermobility (JH) is a condition that can be either benign or accompanied by pain and early development of osteoarthritis. For early verification of the risk of complications, it is necessary to study the molecular pathogenesis of various JH variants. The aim of the study: The aim of this study was to search for candidate genes involved in connective tissue metabolism and causing joint hypermobility in a form isolated or combined with connective tissue dysplasia (CTD). Materials and methods: The study involved young (21,86±0,22 y.o.) people (n=181). A clinical study was conducted for the presence of signs of JH (Beighton scale) and CTD (tables Kadurina T.I.). Further, a molecular genetic study was carried out and the search for associations of polymorphic variants of genes (vitamin D receptor (VDR), lumican (LUM), tenascin (TNXB), growth/differentiation factor 5 (GDF5), magnesium ion channel TRPM6), bone morphogenetic protein type 5 (BMP5)) and JH, CTD in isolated and combined forms. Statistical data processing was carried out by comparing qualitative features using the χ2 test, Fisher's exact test, and the χ2 test with Yates' correction for contingency tables 2x2. The strength of associations was assessed in terms of the odds ratio (Odds Ratio, OR, at p<0.05), the correction for multiple comparisons was carried out using the FDR method (Benjamin- Hochberg). Quantitative data were evaluated in pairs using the Student's t-test, the normality of distribution according to the Kolmogorov-Smirnov test. Results: Associations of the G allele and the GG genotype of the rs3734444 locus of the BMP5 gene with the presence of JH (OR=3.70 and OR=5.10), the A allele of the rs1470527 locus of the BMP5 gene and the presence of JH+CTD- (OR=8.00), the T allele and the TT genotype of the rs11144134 locus of the TRPM6 gene with JH in isolated (OR=3.00 and OR =10.19) and in the forms combined with CTD (OR=3.17 and OR=11.28), the TT genotype was also associated with the isolated form of CTD (OR=3.74). The GT genotype of the rs73611720 locus of the GDF5 gene was associated with isolated CTD (OR=4.15). No statistically significant associations were found for polymorphic variants rs11540149 (VDR), rs2268578 and rs3759222 (LUM), rs3130342 (TNXB). Conclusion: The G allele of locus rs3734444 of the BMP5 gene is a potential risk marker for JH in general, the A allele of locus rs1470527 is an isolated JH, the GT genotype of locus rs73611720 of the GDF5 gene is a marker for isolated CTD, the T allele of locus rs11144134 of the TRPM6 gene is a marker for JH combined with CTD.

Results of surgical treatment of hernias of the anterior abdominal wall in patients with connective tissue dysplasia syndrome

Relevance. The problem of surgical treatment of hernias of the anterior abdominal wall remains relevant. Despite the introduction of new technologies, the results of surgical interventions cannot be considered satisfactory. The development of hernias and their relapses is facilitated by connective tissue dysplasia syndrome, which manifests as phenotypic signs, disorders of the autonomic nervous system, and morphological changes in the structure of the connective tissue.Objective. To improve the results of surgical treatment of hernias of the anterior abdominal wall in patients with connective tissue dysplasia syndrome.Materials and methods. The study was based on clinical observations and studies of 497 patients with hernias of the anterior abdominal wall. Inguinal (29 %) and postoperative hernias (21 %) predominated. In the structure of recurrent hernias, postoperative (47 %) and inguinal (42 %) hernias were more often observed. Hernioautoplasty was performed in 31 %, plastic surgery using a mesh endoprosthesis — in 54 %, endoscopic hernioplasty — in 15 % of patients. The severity of the clinical, morphological, and metabolic signs of connective tissue dysplasia syndrome was assessed. The concentration of free hydroxyproline in the blood was determined as a marker of connective tissue metabolism. The state of the autonomic nervous system was assessed using variational pulsometry. To assess the state of collagen in connective tissue, a morphological study of the aponeuroses of the muscles of the anterior abdominal wall was performed in the clinic and experiment.Results. The overall incidence of dysplasia in hernias of the anterior abdominal wall was 48 %. The highest incidence of connective tissue dysplasia was detected in recurrent hernias (70 %). Studies of the level of free hydroxyproline in abdominal hernias have shown the dependence of this marker on the degree of connective tissue dysplasia. In cases of recurrent hernias, the highest intensity of collagen biodegradation was observed. A study of the functional state of the autonomic nervous system revealed a predominance of sympathetic activity in abdominal wall hernias with an increase in the tension index by more than 4 times. An increase in the severity of dysplasia is accompanied by an increase in sympathetic activity. Histological studies in patients with abdominal hernias revealed characteristic changes in the morphological structure of the connective tissue. The average thickness, specific area, brightness of staining, and orientation of collagen fibers in postoperative and recurrent hernias were significantly different compared to the group with primary hernias (p˂0.05). Additionally, an experiment was performed on 30 laboratory animals (white rats) to determine the optimal conditions for healing of the aponeurosis of the anterior abdominal wall. The activating effect of prozerin on the process of histogenesis in the wound was revealed. Based on the results of the study, the surgical treatment of hernias was assessed depending on the type of hernioplasty and the severity of connective tissue dysplasia. It has been established that with increasing severity of dysplasia, the frequency of relapses increases by 2.2–3.4 times. With the progression of dysplasia, the frequency of relapses increased by more than twice. The use of the endoscopic hernioplasty method reduced the risk of recurrent hernias by 9 times.Conclusion. In externally localized hernias, the incidence of connective tissue dysplasia ranges from 34 % to 70 %. In patients with connective tissue dysplasia syndrome after hernia autoplasty, the frequency of hernia recurrence is 3.4 times higher. Drug correction of sympathetic activity along with alloplasty increased collagen synthesis intensity by 36 %. The choice of hernia repair method should be determined by the type of hernia, the age of the patient, and the severity of connective tissue dysplasia.

Disorders of connective tissue metabolism, which can affect injuries and other risks during sports and physical culture

The purpose of the article: to carry out a theoretical analysis of scientific literature data on disorders of connective tissue metabolism, in particular connective tissue dysplasia, which can cause increased injuries and other negative health consequences when performing physical activity of various types. The article briefly describes changes in the structural elements and metabolism of connective tissue, which can lead to disruption of its basic functions. More often, such changes, according to scientific literature, are described by the term “connective tissue dysplasia” and characterize a variety of all manifestations on the part of most organs and systems of the body. The presence of dysplastic changes in the connective tissue can serve as a prerequisite for the development of many morpho-functional changes, maladaptive changes and the development of pathological conditions in the body of athletes and people involved in physical culture. Against the background of manifestations of connective tissue dysplasia, dislocations, subluxations of joints, episodic arthralgias, tendinitis, bursitis, epicondylitis, tunnel syndrome, protrusions of intervertebral discs, various skeletal deformities, varicose disease of the lower extremities, decreased aerobic productivity, and cases of sudden cardiac death in sports often occur. Thus, timely detection of markers of connective tissue dysplasia will make it possible to rationally select (plan) physical activity in order to prevent cases of injury and the development of other pathological conditions in people involved in physical culture and sports.

Study of chondroprotective properties of interleukin-1 receptor antagonist.

Osteoarthritis is one of the most widespread diseases, represents a medical and socio-economic problem and is one of the first places among the causes of long-term disability of the population in the world. Cytokine mechanisms of osteoarthritis development are attracting more and more attention.
 The aim of the study was to determine the chondroprotective and anti-inflammatory properties of the original recombinant interleukin-1 (IL-1) receptor antagonist (ARIL-1) raleukin on the model of systemic steroid osteoarthritis (SSO) in rats.
 Materials and methods. The SSO model was reproduced in a modified form by intramuscular three-time administration of dexamethasone at a dose of 7 mg/kg with an interval of one week. Raleukin was injected subcutaneously in a conditionally effective dose of 3 mg/kg for anti-inflammatory activity, and glucosamine (GA) orally in a dose of 50 mg/kg (ED50 for anti-inflammatory activity). Starting from the 28th day of the study and for 4 weeks, the study objects were introduced by the appropriate route once a day.
 Result. The results of the experiment show that clinical signs of damage to the locomotor system appeared in all animals after three administrations of dexamethasone. Later and before the end of the experiment, a typical clinical picture of the development of SSO was observed, which was confirmed by the results of the study of biochemical markers (mainly in blood serum) of the state of the connective tissue of the experimental animals.
 Significant changes in the functional status of the animals were noted in rats with SSO who received raleukin starting from the second week of administration. In rats, motor activity increased, tolerance to physical exertion increased, joint condition visually normalised, and appetite increased. When the reference drug GA was administered, the functional state of the animals differed from the control pathology group to a somewhat lesser extent. Besides, raleukin did not reliably differ from GA in its effect on biochemical parameters characterising the state of connective tissue and the content of its main metabolites in the blood serum of rats with steroid osteoarthritis.
 Conclusions. In the model of systemic steroid osteoarthritis, raleukin contributed to the improvement of functional indicators of the condition of animals and the normalisation of their body weight; namely, it moderately reduced the content of all markers of connective tissue metabolism in the blood serum of animals, especially chondroitin sulfates and sialic acids, which can be explained by the systemic nature of its effect. In terms of its effect on the level of the main metabolites of connective tissue in the blood serum of rats, raleukin prevailed over glucosamine hydrochloride. Thus, the analysis of biochemical data against the background of experimental osteoarthritis allows us to draw a conclusion about the high chondroprotective and anti-inflammatory potential of the recombinant IL-1 receptor antagonist

About diverticular colon disease

Relevance. Despite many studies devoted to diverticular colon disease, the results of treatment of this pathology cannot be considered satisfactory. This is primarily due to the fact that the pathogenesis of this pathology has not been fully studied, there are conflicting data on the clinical significance of the level of intraluminal pressure in the intestine and the degree of violation of collagen synthesis in patients. To a certain extent, these criteria can be decisive in assessing the prognosis of the course of the disease in order to timely conduct proactive conservative therapy and adequate surgical aid. The purpose of the study. Improving the results of treatment of patients with complicated course of diverticular colon disease. Materials and methods. There were 194 patients with diverticular colon disease under observation. In 86% of cases, diverticula were localized in the left half of the colon, and isolated sigmoid colon diverticulosis was detected in 68.0% of patients, in the right half — in 4.7% of cases, total diverticulosis — in 9.3% of patients. In patients, the leukocyte intoxication index, the body resistance index, the neutrophil reactive response, the determination of connective tissue dysplasia, connective tissue metabolism indicators, and the measurement of intraluminal pressure in the sigmoid colon were calculated. Results. Conservative therapy was effective in 158 patients (81.4%). Surgical treatment was required for 36 patients (18.6%), with perforation of the diverticulum — in 13.4%, with stenosis — in 5.2% of cases. The nature of the operation was determined by the localization of diverticula and the variant of complication. Postoperative mortality was 2.8%. It was found that connective tissue dysplasia is observed in all patients with diverticular disease, mild — in 36.6% of patients, moderate — in 63.4%. When assessing the intraluminal pressure in 46 patients, its increase was found in all variants of the course of diverticular disease. The average intraluminal pressure was 13.5 ± 0.4 mm Hg. The maximum pressure level was detected in patients with uncomplicated course of the disease. With the development of complications, a decrease in intraluminal pressure was noted. A decrease in intraluminal pressure to 12 mm Hg or less was an unfavourable factor and a predisposition to the development of a complicated course of the disease. The following signs had a significant effect on the recurrence of the disease: age (61-68 years), complications, duration of the disease (more than 4 years), the size of the diverticulum mouth (less than 0.6 cm and more than 1.0 cm), leukocyte intoxication index (more than 2.4 conventional units), the maximum number of rows of the muscle plate of the mucosa and muscle membranes (more than 8.3 and 84 respectively). Conclusions. To predict the course of diverticular disease, a comprehensive analysis of the age of patients, the stage of the disease and its duration, the diameter of the diverticular mouth, the sum of alternative signs of trouble, leukocyte intoxication index, the reactive response of neutrophils, the number of rows of myocytes of the muscle plate of the mucosa and muscle membranes is necessary. Their evidentiary value exceeds 70%. The level of intraluminal pressure in the colon can act as a criterion for the complicated course of diverticular disease.

Матриксные металлопротеиназы — перспективная терапевтическая мишень для лечения остеоартрита

Osteoarthritis (osteoarthrosis) is one of the most common pathologies of the musculoskeletal system, primarily among the elderly, who present typical clinical symptoms such as joint pain, swelling, stiffness and motion limitation. This can lead to a decrease in physical activity and quality of life, in addition to increasing the socio-economic burden on patients and society as a whole. According to data from 2017, more than 303 million people worldwide suffer from osteoarthritis, which makes this disease socially significant. Consonant to modern concepts, osteoarthritis is a joint disease characterized by cellular stress and degradation of the extracellular matrix resulting from macro/micro-injuries that activate pathological adaptive restorative responses, including pro-inflammatory pathways of the immune system. A long-term research period into the pathogenesis of this disease did not allow the development of treatment and prevention techniques that would completely solve the problem of osteoarthritis high incidence. Currently, a pertinent research area is the investigation of this disease phenotypes with particular emphasis on phenotypes associated with inflammation and connective tissue metabolism. An urgent task is to identify the factors regulating these conditions, namely pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukins 1, 6, 18 and catabolism enzymes — matrix metalloproteinases (MMPs), since they can become potential new therapy targets. Most MMPs, including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13 and MMP-14, are involved in the metabolism of the extracellular matrix and the associated destruction of articular cartilage in osteoarthritis. This article is devoted to determining the role of inflammatory mediators, MMPs in the osteoarthritis pathogenesis and reviewing new pathogenetically justified treatment options for this disease. KEYWORDS: osteoarthritis, inflammation, matrix metalloproteinases, therapy targets, connective tissue. FOR CITATION: Tyurin A.V., Gaydukova I.Z., Akhiyarova K.E., Galina I.I., Khusainova R.I. Matrix metalloproteinases are a promising therapeutic target for the osteoarthritis treatment. Russian Medical Inquiry. 2024;8(7):400–405 (in Russ.). DOI: 10.32364/2587-6821-2024-8-7-5.

INDICATORS OF COLLAGEN METABOLISM, CONTENT OF MICRO- AND MACRO ELEMENTS AS BIOMARKERS FOR PREDICTING CHANGES IN DENTAL STATUS IN RATS WITH EXPERIMENTALLY INDUCED FETAL MACROSOMIA

Diseases that manifest in adult life are largely "pre-programmed" already in utero. Fetal macrosomia defined as a body weight at birth of 4.000 grams or more is a condition associated with a range of immediate and long-term consequences. Objective. This study is focused on determining the indicators of collagen metabolism and the exchange of micro- and macroelements in the blood serum of experimental animals born macrosomic. The aim is to establish if any of prognostic markers for the emergence of dental disorders can be found. Material and Methods. Rats of Wistar Albino Glaxo population born with induced macrosomia were used as the test animals. The markers for connective tissue metabolism (free and bound oxyproline) as well as levels of calcium, potassium, copper, magnesium, and zinc were analyzed in the serum of 104 rats in total. The animals were divided into groups immediately after birth according to their weight-height parameters and were sacrificed on the 1st, 90th, 180th, 360th, and 540th day after their birth. Research Results. In the blood serum of animals born macrosomic but with a relative insufficiency of body weight (a weight-height index was lower than that in the control group), as well as in animals with «harmonious intrauterine development» (a weight-height index was comparable with that in the control group), a decrease in copper concentrations by 5–20% and decrease in magnesium levels by 20–40% were registered. Also, reduction by factor 1.4 of the bound fraction of oxyproline and an increase of no more than by factor 1.7 of its free fraction were found. Such biochemical changes precede the formation of periodontal disease. In animals born with "intrauterine obesity" (a weight-height index was higher than that in the control group) and who had the highest intensity of caries among all animals, biochemical changes emerged at an earlier stages of the monitored lifespan. In the serum of such animals, a decrease in magnesium levels by 13–38%, a decrease in zinc by 4–12%, and an increase of up to 11% in copper levels were found. A reduction in the bound fraction of hydroxyproline by factor 1.2–1.4 and an increase in its free fraction by factor 1.4–2.6 were also observed. According to the performed correlation analysis, the significance of the relationship (degree of correlation or anticorrelation and their reliability) between the studied indicators and caries was proven to increase for older animals. Conclusion: In animals born macrosomic, mineral metabolism as well as significant changes of in the organic component in their connective tissue leading to alterations in the bone tissue of the periodontium and the hard tooth tissues. Biochemical changes in the blood serum of rats precede the development of periodontal tissue diseases and carious lesions in ontogeny and depend on the weight-height parameters of the animals at birth.

Нарушения метаболизма аминокислот крови и мочи у детей с диспластическими деформациями позвоночника и грудной клетки

The purpose — to study the content of amino acids in the blood and urine of children with undifferentiated connective tissue dysplasia, having spine and chest deformities. Material and methods. 81 children with undifferentiated connective tissue dysplasia aged 7–17 years were examined. The main group consisted of 49 children with spinal and thoracic deformities; the comparison group consisted of 32 children without spinal and thoracic deformities. The state of the free amino acid pool was assessed by thin-layer chromatography. The blood content and daily urinary excretion of 22 free amino acids and their derivatives were determined. Results. We found that in children with undifferentiated connective tissue dysplasia, changes in the content of proline in the blood were most common in 73 (90.1%) and hydroxyproline in 63 (77.8%) patients. In patients with spinal and thoracic deformities, the content of all 22 amino acids in the blood was changed; among children without spinal and thoracic deformities, the concentration of 11 amino acids was changed. Changes in the content of amino acids in the urine of children with undifferentiated connective tissue dysplasia were detected more often than changes in their content in the blood. At the same time, there were changes in the content of all amino acids in urine among patients. Most often, in children with undifferentiated connective tissue dysplasia, changes in the content of proline were recorded in urine in 73 (90.1%) and hydroxyproline in 65 (80.3%) patients. Less frequently, there was a change in the content of lysine — in 49 (49.4%), ornithine — in 32 (39.5%), phenylalanine — in 29 (35.8%). In children with deformities of the spine and chest, the altered content of amino acids in urine was more common than in patients without deformities. Conclusions. The revealed changes in the content of amino acids in the blood and urine of children with undifferentiated connective tissue dysplasia reflected a violation of their metabolism in the structural components of connective tissue, which led to a violation of its structure and functions. The formation of deformities of the spine and chest can be considered as a clinical manifestation of deep biochemical disorders of connective tissue metabolism in children with undifferentiated connective tissue dysplasia.

Some parameters of connective tissue metabolism in genital prolapse

Genital prolapse (GP) is one of the most common gynecological problems, with an incidence of 28-39%. The problem is exacerbated by the fact that about 1/3 of all these patients are women of reproductive age. And with age, GP becomes progressive. We examined 63 women with the GP of reproductive age who applied to the 8th maternity complex in Tashkent. We found that in women, genital prolapse in 57.1% of cases is due to uCTD. It was found that the severity of GP development depended on the severity of uCTD. In women with GP and uCTD, the magnesium level was significantly lower by 1.8-2 times than in the group without pathology. In more than half (69.4%) of women with GP and uCTD, the excretion of OP was significant and exceeded the due value by more than 2 times. In almost a third (30.6%) of patients, the increase in this indicator was moderate and averaged 76.1±1.9 mg/day.

Assessment of connective tissue metabolism in patients with head and neck malignancies treated with radiotherapy.

<br><b>Introduction:</b> Despite the use of highly specialized irradiation techniques in the treatment of head and neck tumors, it is still impossible to selectively destroy cancer cells without damaging normal structures, including connective tissue cells.</br> <br><b>Aim:</b> The aim of the study was to analyze the concentration of degradation markers such as collagen type I (carboxyterminal telopeptide of type I collagen; ICTP) and elastin (elastin-derived peptides; EDPs) as well as selected metalloproteinases (MMP-1, MMP-2, MMP-9) in patients with head and neck malignancies undergoing radiotherapy.</br> <br><b>Material and methods:</b> The test group consisted of 56 men, who underwent radical or palliative radiotherapy. The concentrations of ICTP, EDPs, MMP-1, MMP-2, MMP-9 were determined in three blood samples collected from patients prior to radiotherapy, immediately after its completion and 3 months after the therapy.</br> <br><b>Results</b>: Both radical and palliative radiotherapy contribute to a significant increase in the concentration of EDPs. At the time of healing of post-irradiation lesions, the level of EDPs was reduced in both groups. The ICTP concentration was not affected by radiotherapy. No significant differences were observed in the concentration of MMP-1 and MMP-2 before and after radiotherapy. Radical radiotherapy caused a statistically significant late reduction in the concentration of MMP-9. The lowest concentrations of MMP-1, MMP-2, MMP-9 in the serum of patients qualified for palliative radiotherapy were recorded in a samples collected three months post-irradiation.</br> <br><b>Conclusions:</b> The degradation markers of key extracellular matrix structural proteins may be helpful tools in the objective assessment of radiation-induced injuries to the connective tissue.</br&gt.

Serum biochemical indicators in rats of different ages after replacing femoral metaphysis defects with allogeneic bone implants saturated with mesenchymal stem cells

The aim of the study: to evaluate the course of metabolic processes after replacing femoral metaphysis defects with allogeneic bone implants saturated with allogeneic mesenchymal stem cells (MSCs) based on the analysis of serum biochemical indicators of connective tissue metabolism in laboratory rats. Material and methods. A critical-sized transcortical femoral defect model in the femur metaphysis of white rats was used. Blood serum concentrations of glycoproteins, total chondroitin sulfates, total protein and calcium, alkaline and acid phosphatase activity were measured. Results. On the 28th day, in 3-month-old animals with MSC, in comparison with the data of rats without MSC, clear signs of connective tissue formation and bone resorption activity were observed, as evidenced by an increase in serum chondroitin sulfates and acid phosphatase activity. On the 90th day, this group of rats under the influence of MSCs showed signs of decreased bone tissue formation with lower serum activity of alkaline phosphatase. In 3-month-old rats with MSC, signs of the inflammatory process chronization with higher serum concentrations of glycoproteins were detected on the 90th day of the experiment in comparison with data from animals without MSC. In 12-month-old rats with MSCs, signs of bone resorption were documented on the 14th day, which were manifested by a higher serum activity of acid phosphatase with less formation of connective tissue and lower concentrations of chondroitin sulfates. On the 28th day, the effect of MSCs in 12-month-old animals was manifested in the form of a slowdown in bone formation with a decrease in alkaline phosphatase activity. On the 90th day, the connective tissue formation was activated with higher concentrations of chondroitin sulfates in these animals. Conclusions. The studied biochemical indicators in 3-month-old animals showed greater lability. The regeneration phases were faster in 3-month-old animals as well as in animals with alloimplants without MSCs. Injections of allogeneic MSCs together with an allograft immediately after a bone damage, regardless of age, caused signs of bone formation slowing and excessive formation of connective tissue, therefore, the combination of allogeneic MSCs with an allogeneic bone implant is not advisable to use in fresh fractures.

Transcriptomic profiling of mare endometrium at different stages of endometrosis

In the current study, transcriptome profiles of mare endometrium, classified into categories I, IIA, and IIB according to Kenney and Doig, were compared using RNA sequencing, analyzed, and functionally annotated using in silico analysis. In the mild stage (IIA) of endometrosis compared to category I endometrium, differentially expressed genes (DEGs) were annotated to inflammation, abnormal metabolism, wound healing, and quantity of connective tissue. In the moderate stage (IIB) of endometrosis compared to category I endometrium, DEGs were annotated to inflammation, fibrosis, cellular homeostasis, mitochondrial dysfunction, and pregnancy disorders. Ingenuity pathway analysis (IPA) identified cytokines such as transforming growth factor (TGF)-β1, interleukin (IL)-4, IL-13, and IL-17 as upstream regulators of DEGs associated with cellular homeostasis, metabolism, and fibrosis signaling pathways. In vitro studies showed the effect of these cytokines on DEGs such as ADAMTS1, -4, -5, -9, and HK2 in endometrial fibroblasts at different stages of endometrosis. The effect of cytokines on ADAMTS members’ gene transcription in fibroblasts differs according to the severity of endometrosis. The identified transcriptomic changes associated with endometrosis suggest that inflammation and metabolic changes are features of mild and moderate stages of endometrosis. The changes of ADAMTS-1, -4, -5, -9, in fibrotic endometrium as well as in endometrial fibroblast in response to TGF-β1, IL-4, IL-13, and IL-17 suggest the important role of these factors in the development of endometrosis.

Correlations of cytokines, regulating the synthesis of structural macromolecules of connective tissue, in undifferentiated connective tissue dysplasia in adolescent girls

Objective: to study the correlations of serum levels of cytokines, regulating the synthesis of structural macromolecules of connective tissue, in undifferentiated connective tissue dysplasia in adolescent girls with menstrual cycle disorders. Materials and methods: 176 adolescent girls aged 11 to 17 years with menstrual cycle disorders (MCD) and undifferentiated connective tissue dysplasia (UCTD) and 69 healthy girls of the same age were examined. Levels of cytokines IL-1β, IL-4, IL-6, IL-10, IL-17A, TNF-α, OPG, RANKL were studied in serum samples. Results: a significant increase in serum IL-6 and RANKL (p<0,01), as well as a tendency (p<0,1) to increase OPG production was found in adolescent girls with UCTD with MCD. In UCTD with NMC, correlations between the studied cytokines are much more common than in the control group (p=0,01). The most pronounced in adolescent girls with UCTD are positive correlations (moderate strength) between the concentrations of three cytokines IL-6, RANKL and OPG. Conclusions: The data obtained reflect the mechanisms of cytokine dysregulation of metabolism and remodeling of connective tissue and indicate the development of a weakly expressed systemic inflammatory process in UCTD with MCD in adolescent girls. The results of the study can be used to develop effective individualized schemes of therapeutic and preventive measures.

The role of connective tissue metabolism disorders in the genesis of stress urinary incontinence in premenopausal women

Research objectives: to study the pathogenetic links in the development of stress urinary incontinence (SUI) by determining the state of connective tissue (CT), concentrations of trace elements, vitamins and estradiol in premenopausal women.Materials and methods. 189 women aged 45–55 years with SUI were examined. In addition to general clinical examination, concentrations of Total PІNP (type I collagen synthesis marker) and Total PІІІNP (type III collagen synthesis marker) and CT resorption marker Pyriliks-D, ionized magnesium, ionized calcium, total calcium, vitamins D and C, estradiol were studied in the blood serum in order to determine the state of fibrous CT.Results. In the structure of somatic morbidity were conditions defined as phenotypic manifestations of CT undifferentiated dysplasia. A decrease of the Total PІNP by 24.9% was found against the background of an increased Total PІІІNP by 46.7% and an increased Pyriliks-D by 54.1%. Women with SUI were characterized by a significant decrease in the average value of Mg2+ by an average of 16.7%, as well as a significant increase in the average value of Ca2+ by 5.3% and total Ca by 3.9%. The vitamin balance study shows a significant decrease of vitamin D by 40.6% and vitamin C by 37.0%. Estradiol concentration was at the minimum values of the physiological norm.Conclusions. Women in premenopausal age with SUI are characterized by a violation of the CT synthesis and resorption, which are realized by reducing the formation of the Total PІNP against the background of intensification of the Total PІІІNP and Pyriliks-D synthesis, combined with a disbalance of vitamins and trace elements. These features are highly likely to be considered as predictors of the SUI development in women of premenopausal age

BIOCHEMICAL INDICATORS OF BLOOD SERUM OF RATS OF DIFFERENT AGES AFTER FILLING THE DEFECT IN THE METAPHYSIS OF THE FEMUR WITH ALLOGENEIC BONE IMPLANTS

Bone defects that do not heal on their own are a significant problem in orthopaedic and trauma surgery. One of the approaches to its solution is the use of bone alloimplants (AloI). Objective. On the basis of the analysis of biochemical indicators of the metabolism of connective tissue in the blood serum of laboratory rats, the course of metabolic processes after the filling of the defect in the metaphysis of the AloI femur was evaluated. Methods. A model of creating a transcortical defect of critical size (diameter 3 mm, depth 3 mm) in the metaphysis of the femur of 3- and 6-month-old rats was used. In animals of groups I (n = 15, age 3 months) and III (n = 15,12 months) the defects were left unfilled, II (n = 15, 3 months) and IV (n = 15, 12 months) — filled with structural AloI. After 14, 28 and 90 days, the content of glycoproteins, total chondroitin sulphates (CS), protein and calcium, activity of alkaline and acid phosphatases in blood serum was investigated. Results. The introduction of AloI leads to an increase in the content of glycoproteins for all periodsof observation in rats of both age groups. 14 days after implantation in 12-month-old rats, compared to 3-month-old rats, a 1.30 times higher level of CS in blood serum was determined (p = 0.008), which is due to their higher content in the area of connective tissue implantation; the activity of alkaline phosphatase decreased by 1.80 times p = 0.016) and acid phosphatase by 1.50 times (p = 0.018), which indicates a delay in the formation and reorganization of bone tissue. However, the level of CS under the conditions of the establishment of AloI on the 90th day was lower compared to the correspondinggroups without plasticity of the defect: in 3-month-old rats by 1.44 times ( p = 0.008), in 12-month-old rats by 1.52 times (p = 0.008). Conclusions. According to the indicators of biochemical markers of connective tissue metabolism, the use of AloI for plasticity of defects of a critical size in the metaphysis of the femur of rats leads to the activation of bone regeneration with a greater manifestation in younger recipients compared to groups with an unfilleddefect.

Analysis of the relationship between degenerative changes in the joint under conditions of hip osteoarthritis with hemostasis disorders in patients based on the results of a biochemical study

Venous thromboembolism is one of the serious complications that occurs after total hip arthroplasty (THA). Among the risk factors may be the presence of disorders of hemostasis and fibrinolysis in patients before surgical intervention. The aim of study to identify the influence of hip osteoarthritis III–IV stages on the hemostasis of patients before performing THA. Methods. A prospective study was conducted with the participation of 60 patients with hip ostheoarthritis III–IV stages and 30 healthy volunteers (control group). Blood and urine samples were obtained from all participants (in patients — one day before THA). Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, fibrinolytic activity (FA), soluble fibrin monomer complexes (SFMCs), glycoproteins, sialic acids, chondroitin sulfates (CS), acid and alkaline phosphatases, β lipoproteins were determined in the blood; in urine — oxyproline, uronic acids, Ca and P. The Pearson correlation coefficient (r) was calculated to determine the relationship between markers of hemostasis and connective tissue metabolism. Results. Compared with the control group, the level of alkaline phosphatase in the blood of patients with hip ostheoarthritis level of glycoproteins (r = 0.97; p < 0.05), cholesterol (r = 0.91; p < 0.05); the level of SFMCs was correlated with the level of glycoproteins (r = 0.99; p < 0.05), CS (r = 0.94; p < 0.05). Conclusions. In patients with hip ostheoarthritis III-IV stages the levels of connective tissue markers (glycoproteins, CS) correlate with the levels of hemostasis markers (fibrinogen, SFMCs). This is of clinical significance for the timely prevention of the development of thromboembolic complications in patients to whom THA is recommended.