Connective Tissue Metabolism Research Articles

Changes in the indicators of connective tissue metabolism in the blood serum of experimental rats under the conditions of modeling the development of degenerative processes in paravertebral muscles

Low back pain is a common health problem. To deepen the understanding of the pathogenesis of the disease, experimental studies on animals with modeling of the pathological process are necessary. Objective. Based on the analysis of biochemical markers of connective tissue metabolism in the blood serum of laboratory rats, the applicability of the studied models of degenerative muscle tissue damage to study the relationship between this condition and the development of disorders in spinal motor segments was assessed. Methods. Two models of reproduction of degenerative processes in the paravertebral muscles of white rats were tested: I (n = 5) — alimentary (diet-induced) obesity, by keeping it for 3 months on a high-calorie diet; II (n = 5) — ischemia, by tying the large rectus muscles of the back with suture material (45 days). Control group (n = 5) — intact animals of similar age and sex. The content of glycoproteins, total chondroitin sulfates (CS), hexosamines, protein-bound hexoses, seroglycoides, fractional distribution and total content of hydroxyproline and glycosaminoglycan sulfates (GAGs) were investigated in the blood serum of rats. The results. In the blood serum of rats of groups I and II, a significant increase compared to the control level of glycoproteins was determined, with a greater effect in the ischemia model, but no significant changes of protein-bound hexoses, hexosamines and CS were recorded. The level of inflammatory markers (sialic acids and seroglycoides) in the blood serum of animals of both groups did not differ significantly from the control, and changes in the parameters of hydroxyproline (except for the slightly changed protein-bound fraction) and GAGs were significant only for the ischemia model. Conclusions. Based on the analysis of biochemical markers of connective tissue metabolism in rats of groups I and II, changes characteristic of degenerative processes were determined, with a greater manifestation in the ischemia model. No significant increase in biochemical markers of inflammation was recorded. Both models can be used to reproduce dystrophic processes in osteochondrosis.

PECULIARITIES OF CONNECTIVE TISSUE METABOLISM IN PATIENTS WITH POST-INFARCTION REMODELING AND REPERFUSION SYNDROME

Early restoration of coronary blood flow in acute myocardial infarction with elevation helps reduce the area of myocardial necrosis, prevent dilatation of the ventricular cavity, and reduce the development of arrhythmias and mortality. However, despite modern technologies in STEMI treatment, the development of reperfusion syndrome, in particular, arrhythmias, is possible after the restoration of blood flow in the infarct-related artery, which is a consequence of acute cellular, metabolic and local electrophysiological changes in the myocardium.
 The aim: is to investigate the long-term effects of reperfusion syndrome on the catabolic/anabolic activity of connective tissue and the processes of connective tissue framework formation in the post-infarction period in patients with myocardial infarction.
 Materials and methods. The study involved 156 patients with acute myocardial infarction with ST segment elevation (STEMI), and 15 apparently healthy individuals (control of laboratory parameters). The average age of the patients was (57.8±1.2) years. The percent of male patients prevailed (76 %).
 All MI patients were divided into two groups: Group I (98 people) – MI patients without clinical signs of reperfusion syndrome during revascularization, Group II (58 people) – MI patients with the signs of reperfusion syndrome in the form of rhythm and conductivity disturbances during revascularization of coronary arteries by percutaneous coronarography intervention (PCI) with prolonged stenting of the infarct-dependent coronary artery.
 Peculiarities of connective tissue metabolism were studied by the content of free and bound oxyproline, glycosaminoglycans, and antibodies to atypical collagens (Ig M and Ig G) in blood serum.
 Results. The recovery period after myocardial infarction showed an increase in collagen catabolism over collagen synthesizing processes in patients with MI who had reperfusion syndrome. The described patterns were also established by changes in glycosaminoglycans. The study showed an increase in the level of antibodies to atypical collagens. Particularly, the level of Ig M, which was within the norm (0.43±0.18) ng/ml, in patients with MI without reperfusion manifestations was three times higher (p<0.001), and in cases of combination of MI and reperfusion syndrome – the highest (p<0.001).
 Conclusions:
 
 Changes in collagen-synthesizing processes are observed in patients with MI, with a tendency to increase the processes of catabolism of the connective tissue matrix.
 The presence of reperfusion syndrome manifestations in MI patients after revascularization aggravates the processes of catabolism, even in the recovery period after MI.
 Increase in the activity of catabolic processes stimulates fibrosis and formation of rigid matrix and atypical collagen, to which antibodies are synthesized, thus blocking the pathological circuit of restructuring of the heart connective tissue framework, and accordingly its pathological remodeling.
 The obtained study results contribute to the identification of more sophisticated approaches to revascularization techniques to avoid negative effects of reperfusion syndrome, as well as new effective medications for collagen synthesis correction, which can increase the effectiveness of rehabilitative management of such

Association of ID polymorphism of the CASP8 gene with vibration disease

Introduction. The study of the contribution of molecular genetic markers to the formation of occupational diseases is currently an urgent direction in occupational health. It is considered proven that the development and course of occupational diseases depends not only on the occupational risk, but also on the individual characteristics of the body of workers. The study of molecular genetic markers makes it possible to determine the risk groups of early development and unfavorable course of occupational diseases in the post-contact period. The study aims to explore the association of the ID polymorphism of the CASP8 gene with vibration disease, the timing of its development and some biochemical parameters. Materials and methods. We have examined eighty men with vibration disease. Of these: twenty three people with early stages of disease development (work experience under the influence of industrial vibration for less than fifteen years), fifty-seven people with late stages of disease development (work experience under the influence of industrial vibration for more than fifteen years). The scientists have carried DNA extraction from blood by the phenol-chloroform method. In the caspase 8 gene (CASP8) in the promoter we have checked the presence/absence of detention in 6 bp652 AGTAAG ins/del (rs3834129) using PCR.The researchers carried out the frequencies of the genotype and alleles of the I/D polymorphism of the CASP8 gene in the studied groups. Results. The authors found that the genotype ID of the rs3834129 polymorphism of the CASP8 gene is significantly more common in the group of patients with late-onset vibration disease (VD). The researchers found when studying some indicators of connective tissue metabolism, that the level of uronic acids (UC) was significantly lower in carriers of the genotype ID polymorphism of the CASP8 gene compared with carriers of other genotypes. Conclusion. The carriage of the genotype ID of the rs3834129 polymorphism of the CASP8 gene is a marker associated with resistance to the formation of VB in workers of vibration-hazardous professions, as well as with a low level of activity of fibroplastic processes. Limitations. The relatively small size of the studied groups. Ethics. The authors have conducted the study in compliance with the Ethical principles of conducting medical research with the participation of a person as a subject and the rules of clinical practice in the Russian Federation approved by Order of the Ministry of Health of the Russian Federation No. 266 of 19.06.2003. The conclusion of the Ethical Committee at the Federal State Budgetary Educational Institution of the Ministry of Health of the Russian Federation (Protocol No. 65 of 27.05.2014) and informed consent of patients was received.

Hepatoprotective Activity of Merremia tridentata against Carbon Tetrachloride Induced Hepatotoxicity in Rats

Objectives: Liver performs a variety of function including storage and purification of blood, secretion of bile, synthesis of plasma proteins and drug detoxification. In an attempt to study the biochemical and connective tissue metabolism during the progression of hepatic fibrosis and to gain more insight into the mechanisms leading to the altered metabolic processes in human hepatic fibrosis, an experimental animal model was developed using administration of carbon tetrachloride (CCl4). Methods: The present study evaluates the hepatoprotective activity of Merremia tridentate plant extract against CCl4 induced liver damage in Wistar albino rats. CCl4 caused a rise in liver and serum AST, ALT, ALP, ACP and total Bilirubin content. Pretreatment and post treatment of rats with ethanolic and aqueous extracts (50,100 & 200 mg/kg b.wt) significantly reduced these serum parameters and antioxidant enzymes levels compared to CCl4 induced rats. The post-treatment had better activity than the pre-treatment groups. Findings: Preliminary phytochemical analysis showed the presence of tannins, saponins, flavonoid, alkaloid, anthocyanin, quinones, glycosides, cardiac glycosides, terpinoids, phenol, coumarin and reducing sugar which may be responsible for the hepatoprotective activity. The liver stabilization activity is due to the presence of bioactive compounds in the Merremia tridentate extracts. Conclusions: Thus, Merremia tridenta extracts ameliorated the liver damage caused by the CCl4and raised the liver and serum enzymes to normal levels: Keywords: Liver; Detoxification; Carbon Tetrachloride; Merremia trident; Hepatotoxins

Informativeness of biochemical markers of connective tissue metabolism in canine babesiosis

The aim: to analyze the diagnostic informativeness of biochemical markers of connective tissue in the blood of dogs with babesiosis.
 Materials and methods. German Shepherd (n=7), Labrador Retriever (n=3) and Rottweiler (n=2) dogs aged 1 to 5 years and diagnosed with babesiosis were studied. As a control group, clinically healthy dogs were used, which came to the veterinary clinic for a preventive examination, the age of the animals was from 1 to 5 years (n=10). The animals were examined according to the following scheme: collection of anamnestic data, clinical examination according to generally accepted methods, general and biochemical blood analysis, urine examination. Glycoproteins in blood serum were determined according to Shteinberg – Dotsenko, sialic acids – according to the Hess method, chondroitin sulfates – Nemeth–Csoka in the modification of L.I. Slutsky.
 Results. The biochemical examination of the blood revealed the presence of acute cytolytic syndrome and cholestasis in the animal's body. Cholestasis in sick animals was characterized by an increase in the content of bilirubin and the activity of alkaline phosphatase, as well as an increase in the content of β-lipoproteins. The increase in the content of total bilirubin in the blood was obviously due mainly to its unconjugated fraction, since intravascular hemolysis took place. In the blood serum of patients with babesiosis in dogs, there was an increase in the content of markers of connective tissue metabolism – glycoproteins by 1.63, sialic acids – by 1.36, and chondroitin sulfates by 1.8 times, respectively.
 Conclusions. Glycoproteins have "acute phase proteins" in their composition, which are indicators for assessing the degree of the inflammatory process in the body of dogs with babesiosis. Sialic acids are components of sialoproteins, which are also markers of the inflammatory process and destructive changes in the body. An increase in the content of chondroitin sulfates in the blood during babesiosis indicates the development of a compensatory reaction, associated with the action of toxic hemolysis products on the endothelium of blood vessels. Thus, the increased content of biochemical markers of connective tissue in the blood of dogs with babesiosis indicates the presence of a systemic inflammatory-protective reaction in animals, which makes it possible to recommend them for assessing the acute phase of the inflammatory process in the body and protecting blood vessels from damage due to toxic hemolysis

Indicators of connective tissue biopolymers in healthy pregnant women

Objective. To detect the features of connective tissue metabolism in healthy women during pregnancy.
 Materials and methods. The study of the connective tissue components was conducted at the terms of 1516 weeks, 2024 weeks as well as before the labor. Under observation there were 52 pregnant women (main group), who underwent the study of the connective tissue components in dynamics of pregnancy and 39 patients (comparison group) the study of the connective tissue biopolymers before pregnancy. The main protein of connective tissue collagen was studied by a quantitative determination of amino acids of the free- and peptide-bound hydroxyproline. Metabolism of glycoproteins was investigated according to the concentrations of free oligo-bound and protein-bound sialic acids, oligo-bound and protein-bound fucose, fucosidose and hyaluronidase activity. Seromucoid, hexasamine and glycosaminoglycan content was analyzed.
 Results. There was established a statistically significant increase in the blood serum free and piptide-bound hydroxyproline content, the absence of changes in the blood serum glycoprotein concentration, the growth of glycosaminoglycan concentrations and fucosidase concentrations beginning from the week 20 of pregnancy, the elevation of protein-bound sialic acid concentration from the weeks 2024 of pregnancy, free and oligo-bound sialic acids from the week 37 in the blood serum.
 Conclusions. The study results indicate that among healthy women, disorganization and structural changes in the connective tissue during pregnancy are based on the changes in the anabolic and catabolic processes conditioned by improvement of the humoral control of metabolism.

ORAL REHABILITATION WITH DENTAL IMPLANTS IN A PATIENT WITH HADJU-CHENEY SYNDROME: CASE REPORT

Hadju-Cheney syndrome (HCS) is a rare disease of the connective tissue and bone metabolism. This osteolytic disorder follows an autosomal-dominant inheritance pattern, and some manifestations are acro-osteolysis, osteoporosis, short stature, craniofacial changes, progressive periodontitis, premature tooth loss, and dental abnormalities. The proband was a 21-year-old male patient with HCS with the chief complaint of pain and chewing difficulty due to teeth mobility. Clinical examination showed generalized advanced periodontitis. However, computed tomography showed satisfactory basal bone height. For oral rehabilitation, total teeth extraction and dental implant was proposed. First, total extraction of the maxillary teeth and 6 dental implants were performed. In the second surgery, total extraction of the mandibular teeth and 4 dental implants were performed. Six months after the first surgery and successful osseointegration of the dental implants, an implant-supported dental prosthesis was placed. The oral rehabilitation provided a more aesthetic appearance, with better masticatory performance and quality of life. Hadju-Cheney syndrome (HCS) is a rare disease of the connective tissue and bone metabolism. This osteolytic disorder follows an autosomal-dominant inheritance pattern, and some manifestations are acro-osteolysis, osteoporosis, short stature, craniofacial changes, progressive periodontitis, premature tooth loss, and dental abnormalities. The proband was a 21-year-old male patient with HCS with the chief complaint of pain and chewing difficulty due to teeth mobility. Clinical examination showed generalized advanced periodontitis. However, computed tomography showed satisfactory basal bone height. For oral rehabilitation, total teeth extraction and dental implant was proposed. First, total extraction of the maxillary teeth and 6 dental implants were performed. In the second surgery, total extraction of the mandibular teeth and 4 dental implants were performed. Six months after the first surgery and successful osseointegration of the dental implants, an implant-supported dental prosthesis was placed. The oral rehabilitation provided a more aesthetic appearance, with better masticatory performance and quality of life.

The role of connective tissue biopolymers in the pathogenesis of dog bronchopneunmonia and cat brochnial asthma

The aim: to analyze the pathogenetic role of connective tissue biopolymers in canine pneumonia and feline asthma.
 Materials and methods. The study was conducted by analyzing the sources of scientific literature: PubMed, Elsevier, electronic resources of the National Library, named after V.I. Vernadsky and the results of our own scientific and clinical experience.
 Results. Studies on the pathogenetic justification of the role of biochemical indicators of the connective tissue in the diagnosis and treatment of diseases of the respiratory system of dogs and cats were conducted. This is due to the need to expand knowledge about the peculiarities of the course, to determine the leading pathogenetic links of the most common pathologies –bronchopneumonia and bronchial asthma, which are found in clinical veterinary practice.
 Conclusions. In bronchopneumonia of dogs on the background of severe clinical symptoms (cough, fever, wheezing in the lungs), radiological signs (inhomogeneous compaction of the lung tissue, lack of clear contours of the bronchi), anemic syndrome, general and neutrophilic leukocytosis, lymphocytopenia, hypoalbuminemia, dysproteinemia (increased concentration of α2- and β-globulins in the blood serum), hypercholesterolemia, hyper-β-lipoproteinemia, hyperfermentemia (increased activity of AST and alkaline phosphatase,) there is an increase in serum glycoproteins and chondroitin sulfates, sialic acids, total glycosaminoglycans (GAG) due to the chondroitin-4-sulfate fraction; urinary excretion of oxyproline and uronic acids increases. Disorders of connective tissue metabolism in dogs with bronchopneumonia are caused by an acute inflammatory process in the lungs with the development of pulmonary fibrosis.
 Bronchial asthma in cats is manifested by intermittent cough, shortness of breath, hypochromic normocytic anemia, leukocytosis, eosinophilia and lymphocytopenia, increased serum activity of AST and alkaline phosphatase, haptoglobin content, glial acid concentration sulfate; urinary excretion of oxyproline and uronic acids increases. Connective tissue disorders in cats with bronchial asthma are caused by increased mucus excretion with a high content of GAG, as well as chronic inflammation of the bronchial mucosa and their fibrosis

Аssociation between incidence of caries of temporary teeth and pathology of the musculoskeletal system in preschool children, considering biochemical markers of connective tissue metabolism

The aim is study biochemical markers of connective tissue metabolism in children with musculoskeletal disorders and their association with dental caries of temporary teeth. There were examined 232 children at the age of 5 (202 children with musculoskeletal disorders and 30 conditionally healthy children without somatic pathology). Among children with musculoskeletal disorders 68 (33.66%) had flat feet, 59 (29.21%) – postural impairment and 75 (37.13%) – combined pathology of the musculoskeletal sestem. For further research, the children were divided into three groups, 30 people in each. Group І included children with pathology of the musculoskeletal system, dental caries, without oxyproline in urine; group ІІ – with pathology of the musculoskeletal system, dental caries and oxyproline in urine; group ІІІ – with dental caries and without oxyproline in urine. Urinary excretion of glycosaminoglycans using a nephelometric test with cetylpyridinium chloride was determined. The concentration of creatinine in urine was measured in units of weight in the formation of a chromogenic complex of a solution of picric acid with creatinine in an alkaline medium. Dental status was assessed in terms of caries prevalence, deft index and severity of dental caries. The prevalence of caries of temporary teeth in 5-years old children with musculoskeletal disorders was on average 90.6±2.05%, deft index ─ 6.62±0.20, being significantly higher than in children without somatic pathology (respectively 70.83±4.45% and 5.15±0.34, р<0.001). Oxyprolin was detected only in the urine of children with combined pathology of musculoskeletal system (on average 3.53±0.11 units). The excretion rates of glycosaminoglycans in children with pathology of the musculoskeletal system, dental caries and oxyproline in urine (gr.ІІ) were two times higher than the reference range (415.37±15,09 CPCh units / 1 g creatinine, р<0.001). In the absence of oxyproline in urine, both in somatically healthy children (gr. ІІІ) and in children with pathology of the musculoskeletal system (gr. І), the levels of excretion of glycosoaminoglycans were within the reference range (respectively 198.83±10.71 and 203.87±12.52 CPCh units / 1 g creatinine. The levels of daily excretion of creatinine were within the normal range in children of gr. ІІІ (1.17±0.13 g/day; in children of gr. І they were 2.85 times lower (0.41±0.05 g/day, p<0.001); in children of gr. ІІ – 6.5 times lower (0.18±0.02 g/day р<0.001). In children of gr. ІІ, a negative correlation was found between the levels of creatinine and oxyproline (τ= -0.68, p<0.05). The absence of oxyproline in the urine of children of gr. І and ІІІ indicates the absence of collagen decay in their bodies. In children with pathology of the musculoskeletal system against the background of undifferentiated connective tissue dysplasia (gr. ІІ), a strong, positive correlation was found between the deft index and levels of urinary excretion of oxyproline (τ= +0.77, p<0.05) and glycosaminoglycans (τ= +0.90, p<0.05), which indicates that the development of dental caries depends on the severity of the pathology of the musculoskeletal system.

EVALUATION OF METABOLISM PARAMETRES OF CONNECTIVE TISSUE IN TREATMENT OF EXPERIMENTAL PURULENT WOUNDS OF CATS

Wound pathology is one of the most important problems of modern veterinary surgery. Violation of connective tissue metabolism significantly affects occurrence and development of many pathological processes in various organs and tissues, however, parametres of connective tissue metabolism in purulent wounds of cats have not been thoroughly studied. Therefore, their study will allow to substantiate pathogenetically and improve treatment methods of purulent wounds of cats. The studies were carried out from 2010 to 2020 on the basis of the clinic of veterinary medicine and the laboratory of the Department of Surgery and Diseases of Small Animals of Luhansk State Agrarian University, as well as in biochemical and immunological laboratory of Lugansk. Twelve animals were used in the experiment, which were divided into two groups (the first - experimental, the second - control). The ointment "Methyluracil with Miramistin" (Darnitsa) with addition of 1% hyaluronic acid and 1% trifusol were used in the experimental group. Only "Methyluracil with Miramistin" ointment was used for treatment of animals in the control group. Animals underwent daily revision of wounds and local mechanical treatment. For planimetric studies, a ruler and a transparent film with a grid on it with a cell size of 1 cm2 were used. As for animals of the experimental group, content increase of hexoses associated with proteins, hexoses of glycoproteins and sialic acids was recorded only during the period of inflammatory and degenerative changes. Subsequently, starting from the 12th day of the experiment, these parametres decreased to the initial level. As for animals of the control group, the content of hexoses associated with proteins gradually decreased, but was higher than that of cats of the experimental group due to increase of hexoses of glycosaminoglycans. Also, the content of sialic acids in the control group remained high throughout the experiment. Such tendency indicates that application of ointment with addition of hyaluronic acid and trifusol contributes to normalization of the H-GAG / H-GP index, which is typical for a more intensive development of reparative processes. On the contrary, an increase of the healing time of a wound defect of animals of the control group was accompanied by a redistribution of hexose fractions towards an increase in the proportion of glycosaminoglycans. These changes are stipulated by gradual depolymerization and restructuring of the basic substance of the connective tissue in the phase of regeneration and proliferation of the wound process.

Застосування методів консервативної терапії в дітей з післяопіковими рубцевими деформаціями та їх вплив на метаболізм сполучної тканини

One of the factors of scarring is changes in the connective tissue (CT). Defeat of CT is accompanied by changes in the content of glycosaminoglycans (GAG), activity of lysosomal enzymes, levels of mineral metabolism. To eliminate the influence of inflammatory phenomena and disorders of CT metabolism on the formation of scar tissue, it is urgent to use conservative rehabilitation measures. Purpose - to determine the effectiveness of measures of conservative therapy of post-burn scars in children for the clinical course and metabolism of connective tissue. Material and methods. 27 children aged 5 to 18 were supervised. The group of healthy children without clinical manifestations of inflammatory reactions consisted of 17 people. Conservative treatment of children with scarring included local, drug, physiotherapy, balneological and efferent therapy methods. The impact of treatment measures was assessed on a modified scar score scale, which consisted of a patient (parent) scale and a researcher scale. Laboratory criteria of effectiveness were the amount of ceruloplasmin (CP), lactic (MC) and sialic (SC) acids, GAG content, lysosomal enzyme activity (bone and alkaline phosphatase), mineral metabolism (total calcium). Laboratory parameters in patients were studied in the period from 150 to 170 and 310 to 340 days after injury. SPSS v was used for statistical analysis. 17.0. Results. Improvements in clinical signs of scar tissue were 1.7-fold according to objective estimates and 1.6-fold according to patient estimates. Laboratory monitoring showed the effectiveness of conservative treatment of convalescents, which was manifested in a reduction in GAG levels 1.6 times after 6 months and 2.0 times after a year. There was a decrease in the activity of acid phosphatase in 1.6 times, alkaline phosphatase and its bone fraction in 1.4 times. In addition, after treatment, there was an increase in ceruloplasmin activity by 1.5 times at all times. A 1.5-fold increase in the number of MCs was determined at all observation times. After treatment, the amount of MC decreased by 1.2 times (P<0.05). Significant confirmation of an increase in the level of SC in 1.4 times (P<0.05) was observed only on the 160th day of the study. At other times, the increase in the IC was unreliable. Conclusions. Long-term studies have shown that in children after thermal trauma in the process of productive scarring there are deviations in the metabolism of CT in the direction of increasing its synthetic function, metabolic disorders and inflammation continue. The use of complex conservative therapy in children with post-burn scars during convalescence allowed to reduce the severity of inflammatory reactions, improve CT metabolism and reduce scarring. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Key words: post-burn scarring in children, connective tissue, metabolism, inflammation, conservative therapy.

CORRELATION OF INFLAMMATION WITH STRUCTURAL AND FUNCTIONAL CHANGES IN THE RATS’ PROSTATE GLAND WITH CHRONIC PROSTATITIS UNDER THE EXPOSURE OF CHONDROITIN SULPHATE

According to statistics, about 10 % of urological patients in Ukraine have diagnose as well chronic prostatitis/chronic pelvic pain syndrome, or non-bacterial chronic prostatitis. The etiology and pathogenesis continue to be substantially uncertain, but inflammation is one of the triggers that also involves connective tissue. The aim of the work was to evaluate and compare changes of inflammation markers and histological structure of prostate tissue in rats with experimental chronic prostatitis under conditions of Chondroitin sulfate use. Material and Methods. Non-bacterial prostatitis was caused by local irrigation of the previously exposed surgical access to isthmus and ventral parts of the prostate for 5 seconds by an applicator for the wart removal Wartner®, the wounded surface was sewed in afterwards. Non-bacterial prostatitis was caused by local irrigation of the previously exposed surgical access to isthmus and ventral parts of the prostate for 5 seconds by an applicator for the wart removal Wartner®, the wounded surface was sewed in afterwards. To assess the anti-inflammatory and prostatoprotective properties, we used the introduction of the substance Chondroitin sulfate (manufactured by Sigma, USA) and the reference drug Prostoplant forte (manufactured by Schwabe, Germany). The drugs were administered three days before the simulation of cryotraumatic prostatitis and within 11 days after cryotrauma. The state of inflammation was assessed by the level of C-reactive protein, the number of leukocytes, the erythrocyte sedimentation rate in the blood, and during pharmacological correction. The state of the connective tissue was assessed according to the results of histological examination of the prostate. The results of the laboratory and histological studies in the conditions of simulating prostatopathy have been shown that markers of inflammation of the blood and prostate tissue have parallel unidirectional changes. Both drugs have a distinct anti-inflammatory effect and they are able to protect prostate tissue from destructive changes resulting from inflammation. The effectiveness of Chondroitin sulfate did not concede to the comparison drug Prostoplant forte, and was even partly more effective in normalizing the concentration of C-reactive protein C-reactive protein and reconstruction of prostate tissue. Conclusion. These results indicate that the use of a combination of prostatoprotectors and drugs capable of affecting the metabolism and reconstruction of connective tissue is promising for the treatment of prostatitis.

Inherited connective tissue diseases highlight macromolecular network interdependences in skin extracellular matrix: a histomorphometric study

ABSTRACT Mutation of just a single extracellular matrix protein, a receptor or enzyme involved in connective tissue metabolism is sufficient to cause systemic pathologies and failure of tissues that are subjected to strong mechanical stresses. Skin histological and computerized image analyses can provide a good qualitative and quantitative indication of these inherited connective tissue diseases. In this study, skin biopsies from young (10 to 25 years) and middle-aged patients (26 to 50 years) suffering from Ehlers-Danlos syndromes (EDS), Marfan syndrome (MS) or pseudoxanthoma elasticum (PXE) were studied after specific staining of both the collagen and elastic networks. Findings from the histomorphometric analyses conducted on skin sections of the patients with EDS, MS and PXE were compared to skin sections of healthy subjects from the same age groups. Our results show that both the collagen and the elastic networks were affected in all the studied pathological cases, but that the adverse changes to the elastic network in older patients were distinct from the physiological changes observed during aging process for healthy subjects. This degenerative process may be explained by an added phenomenon involving a general connective tissue proteolysis.

ИЗУЧЕНИЕ МИКРОЭЛЕМЕНТНОГО СОСТАВА МЕЖПОЗВОНКОВЫХ ДИСКОВ ПРИ ОСТЕОХОНДРОЗЕ ПОЯСНИЧНОГО ОТДЕЛА ПОЗВОНОЧНИКА

The progressive prevalence, significant economic losses, the cost of compulsory health insurance and high-tech medical care have turned the problem of lumbar osteochondrosis into a socially significant issue. The relevance of this problem is dictated by the need to study the etiopathogenesis of the course of degenerative changes for an integrated approach when choosing an adequate treatment. The progression of the pathological process in the spine significantly contributes to changes in the metabolism of connective tissue, which is closely associated with the violation of microelements. Purpose: Evaluation of changes in the homeostasis of the intervertebral disc, in particular the study of the microelement composition of the intervertebral disc at various stages of development of hernias of the lumbar spine using instrumental neutron activation analysis. Material and methods: The studied biomaterial was obtained intraoperatively, with traditional microdiscectomy in herniations of the spine at the level of VL3-4, VL4-5, VL5-S1. By the method of instrumental neutron activation analysis, a study of biomaterials, represented by tissue fragments of the remote part of the hernia of the intervertebral disc, located at different stages of the degenerative process, was carried out. Results: The quantitative content of 22 macro- and microelements in the removed fragments was determined. As a result of the data obtained, it was found that in the tissues of the intervertebral discs, a gradual change in the content of a number of essential elements occurs, depending on the stage of development of the degeneration process. Conclusion: Changes in the microelement composition indicate metabolic processes occurring in the intervertebral discs, and the relationship of the microelement composition of the disc tissue and the course of the degenerative process can be used to predict the condition of the patient and choose an adequate treatment.

Innate Immunity in the Development of Connective Tissue Dysplasia: Pilot Study in Children with Congenital Hip Dislocation

Introduction: Observing and treatment of hip dysplasia in children have always been in the sphere of interest of modern molecular medicine. The role of molecular factors in the formation of connective tissue dysplasia in children is considered crucial for such multisystem disorders, and connective tissue dysplasia progressing involves immune system parameters and biochemical markers. The aim of this work was to establish the relationship between immune status indicators and biochemical markers of connective tissue using bioinformatics and modeling methods. Materials and Methods: 27 patients with congenital hip dislocation, admitted to the University Clinic of Privolzhsky Research Medical University, Department of children orthopedics for surgical treatment, were examined. Determination of 10 blood parameters was conducted by modern biochemical and immunological methods. Statistica 12.0 software from StatSoft was used for statistical data processing. Methods of nonparametric statistics were used since the samples in the control group partially follow the normal distribution. Correlation methods and regression modeling methods were used to evaluate the relationship of indicators. Results and Conclusion: In our investigation we have shown the presence of statistical and mathematical interactions between the parameters of innate immunity and indicators of connective tissue metabolism. The leading role of the immune system in the development of pathologies associated with connective tissue dysplasia is assumed. In further investigations it is necessary to clarify the role hypoxia in HIF-1 stimulated control of skeletal dysplasia, collagen modification, connective tissue dysplasia development.

ПАТОГЕНЕТИЧЕСКИЕ ПОДХОДЫ К ТЕРАПИИ ПРИ ЭКСПЕРИМЕНТАЛЬНЫХ ИНФИЦИРОВАННЫХ РАНАХ У КОШЕК

Wound pathology is one of the most important problems of modern veterinary surgery. Violation of connective tissue metabolism significantly affects the occurrence and development of many pathological processes in various organs and tissues, but the indicators of connective tissue metabolism in purulent wounds in cats have not been studied enough. Therefore, their study will allow pathogenetically substantiate and improve the methods of treatment of purulent wounds in cats. In animals of the experimental group who were treated with methyluracil with miramistin with the addition of 1% hyaluronic acid and 1% trifuzol, an increase in the content of hexoses associated with proteins, hexoses of glycoproteins and sialic acids was recorded only during the period of inflammatory and degenerative changes. In the future, starting from the twelve days of the experiment, these indicators decreased to the initial level. In animals of the control group during treatment, the content of hexoses associated with proteins gradually decreased, but was higher than in cats of the experimental group due to an increase in the proportion of hexoses of glycosaminglicans. Also in the control group, the content of sialic acids remained high throughout the experiment. This trend indicates that the use of ointment with the addition of hyaluronic acid and trifuzol contributes to the normalization of the G-GAG / G-GP index, which is characteristic of a more intensive development of reparative processes. On the contrary, an increase in the healing time of a wound defect in animals of the control group was accompanied by a redistribution of hexose fractions towards an increase in the proportion of glycosaminglicans. These changes are due to the gradual depolymerization and restructuring of the main substance of the connective tissue in the phase of regeneration and proliferation of the wound process.

Biochemical markers of connective tissue metabolism in the diagnostics of respiratory diseases in human and animals: retrospective analysis (1984–2010)

The aim: to analyze the literature data for the period from 1984 to 2010 on the use of biochemical markers of disorders of connective tissue metabolism in diseases of the respiratory system in humans and animals.
 Materials and methods. The research was conducted by the method of scientific literature open source analysis: PubMed, Elsevier, electronic resources of the National Library named after V.I. Vernadsky (1984–2010).
 Results. In the case of diseases of the respiratory system in humans, the pathogenesis of pneumonia is the development of inflammation in the interstitial, peribronchial, perivascular and perilobular connective tissue, lymphatic vessels of the lungs, followed by involvement of alveoli and bronchioles in the inflammation. The morphological basis of these changes may be pneumofibrosis and pneumosclerotic changes. In the chronic course of pneumonia, chronic obstructive pulmonary disease develops. This pathology is closely related to the action of inflammatory cytokines that regulate connective tissue proliferation. Similar studies were performed on eosinophilic bronchopneumonia in dogs, but the material for the study was bronchoalveolar lavage. The current method of diagnosing respiratory diseases using cytokines (interleukin-4, interferon-γ) and bronchoalveolar lavage has no diagnostic information in chronic bronchitis and bronchial asthma in cats. Fundamental studies of connective tissue biopolymers in clinically healthy and bronchopneumonia piglets have recently been conducted in veterinary medicine.
 Conclusions. Recently, in medicine of particular interest to researchers is the determination of the content in biological fluids of indicators of connective tissue metabolism (hydroxyproline, glycosaminoglycans, glycoproteins, sialic acids) to diagnose diseases of the respiratory system. To diagnose connective tissue disorders in lung diseases in medical practice use indicators of oxyproline in serum and urine. Oxyproline is one of the most important components of lung collagen. An increase in the content of free oxyproline in the blood indicates an increased rate of collagen breakdown in the lung tissue. Analysis of oxyproline fractions, as indicators of the direction of collagen metabolism, allows to assess the condition of the connective tissue of the lungs and can serve as a prognostic criterion for the course of the disease. Thus, the indicators of connective tissue metabolism showed significant diagnostic information, which allowed to recommend them for use in the practice of veterinary medicine.

Application of DataMining clustering and classification methods in the study of the mechanisms of mutual burdening of reactive arthritis and chronic pyelonephritis in terms of connective tissue metabolism

Disorders of metabolic processes in the "proteoglycans-collagen" system, changes in enzymatic reactions in patients with reactive arthritis (ReA) are often preceded by many complications, including impaired renal function. Classical regression methods are not very informative in determining the mutual burden of ReA and chronic pyelonephritis (CP), as well as the primacy of the disease.Objective - to investigate the possible relationship between ReA and CP in order to establish early criteria for predicting the development of CP on the background of ReA on the indicators of connective tissue metabolism. Material and methods. 113 patients were examined, which were divided into two groups: the first group - patients with urogenic ReA, activity I-III. FTS I-III st. (n = 65); the second group - patients with urogenic ReA and CKD I-II: pyelonephritis in the acute phase (n = 48). The control group consisted of 20 healthy individuals. The average duration of the disease of the examined patients was 24.4 ± 4.7 months. The mean age of patients was 32.5 ± 1.2 years. DataMining clustering and classification methods were used to process the obtained research results.Results. As a result of clustering methods (k-means and fuzzy clustering), the same results of cluster membership were obtained. In particular, ReA disease was correctly diagnosed in 48 cases, which is 74% of all diagnosed, 17 people (26%) were assigned to cluster "2". There is also a mismatch in the second cluster. In particular, out of 32 people diagnosed with ReA + CP, according to mathematical calculations, 28 people (88%) got into this cluster. Four patients (13%) were assigned to cluster "1" – to the group of persons in whom only one ReA disease should be diagnosed. This indicates that the boundary between the ReA and ReA + CP clusters are somewhat blurred. And this is the basis for establishing the fact that ReA disease can gradually lead to CP.Conclusions. Using DataMining clustering methods the greatest significance was defined in the diagnostic algorithm of ReA progression of such indicators as free oxyproline (FOP), protein-bound oxyproline (PBOP), the degree of collagenolytic activity (CLA) (intensity of azocol lysis), which showed a direct dependence on the degree of activity of the inflammatory process. Increases in FOP> 13.8 μmol/l, PBOP> 65.0 μmol/l and CLA (azocol)> 0.85 μg / ml in 1 h are probable risk factors for progression and early criteria for severe ReA and CP.

Periarticular lesions as actual problem of general practice: modern possibilities of diagnosis and boosting effectiveness of treatment

Background. Lesions of extra-articular soft tissues occupy a leading place in the structure of diseases of the musculoskeletal system in primary health care. At the same time, insuffcient attention is paid to this pathology, which leads to a decrease in the quality of care for patients with extra-articular pathology.Objective. Increasing the awareness of general practitioners about the clinical forms of extra-articular soft tissue diseases, current approaches to diagnosis and treatment.Basic provisions. The article presents the characteristics of the main forms of periarticular lesions: periarthritis, incl. painful shoulder, tendonitis, tenosynovitis, capsulitis, bursitis. The leading mechanisms of periarticular disorders are presented, the clinical picture and diagnostic signs of particular forms are described. The role of modern methods of visualization of periarticular lesions using ultrasound and MRI is noted. The main approaches to the drug therapy of periarticular disorders are presented, including use of slow-acting symptom-modifying drugs (SYSADOA). The authors present their own data demonstrating the connective tissue metabolism disturbance in periarticular disorders as well as the effectiveness of the drug Alflutop in the treatment of periarticular lesions of a ‘mechanical’ nature.Conclusions. Primary forms of periarticular disorders are a consequence of microtraumatization and can be attributed to ‘mechanical’ types of damage. The ultrasound is pivotal in the diagnosis and evaluation the severity of the lesion and its origin. Biomarkers of connective tissue damage can be detected in the blood of patients with periarticular disorders. The treatment results can be improved with drugs from the SYSADOA group.

Indices of connective tissue metabolism, their interconnection in patients with 5D stage chronic kidney disease and in patients with anterior abdominal wall hernias

Objective. To study the interconnection between the indices of matrix metalloproteinases (MMPs) of type I collagen terminal telopeptides in patients with end-stage chronic kidney disease (CKD) and in patients with anterior abdominal wall hearnias.Materials and methods. 39 patients with CKD stage 5D, 24 patients with primary anterior abdominal wall hernias and 25 patients of the comparison group without visual signs of connective tissue dysplasia were included into the prospective study. The concentrations of the levels of MMP-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-3, N-terminal telopeptide NTX-N, C-terminal telopeptide CTX-C were determined in plasma using the enzyme immunoassay (ELISA).Results. The end-stage patients with CKD and the patients with anterior abdominal wall hernias showed no statistically signifcant biochemical indices of ongoing bone tissue destruction based on the levels of terminal telopeptides NTX-N and CTX-C. There are statistically signifcant increases in the levels of MMP-1, MMP-2, MMP-9 (p ˂ 0.001) in the CKD stage 5D patients and major TIMP-1 and TIMP-3 (p ˂ 0.001) in relation to the comparison group. These indices were comparable with the changes in the connective tissue of the patients with primary anterior abdominal wall hernias.Conclusion. The obtained results indicate disturbances in the regulation of the synthesis and structural relationships of connective tissue in CKD stage 5D patients and in patients with primary anterior abdominal wall hernias. CKD stage 5D patients and primary anterior abdominal wall hernias reveal identical direct correlations in the indices of connective tissue metabolism according to NTX-N, MMP-1 and MMP-9, TIMP-1, which indicates similar disturbances in the regulation of the synthesis and structural disorders in connective tissue.