Connective Tissue Synthesis Research Articles

DYNAMIC CHANGES IN HISTOLOGICAL AND MORPHOMETRIC INDICATORS OF THE LUNGS IN SEXUALLY IMMATURE RATS DURING SIMULATION OF PARTIAL TRACHEAL STENOSIS

Introduction. The morphological features of the respiratory system in laryngomalacia remain insufficiently understood, particularly regarding structural, cytological, and functional alterations. The aim of this study is to investigate the morphological characteristics of the respiratory compartment in the lungs of sexually immature rats, conduct a morphometric assessment of lung tissue density, analyze the dynamics of erythrocyte mass and collagen accumulation, and identify correlations between these parameters. Materials and Methods: The study involved sexually immature male Wistar rats aged 25-28 days and weighing 40-55 g. Partial tracheal stenosis was induced in experimental animals using a developed method, restricting the tracheal lumen by 20-25%. The stenosis was maintained for 7 and 21 days in different groups. In one group, tracheal stenosis was relieved after 7 days by removing the compressive ligature. Histological, histochemical, and morphometric methods were employed to study changes in lung tissue. Results. Pathological changes in lung tissue during hypoxia were characterized by an increase in the number of different types of cells and erythrocyte mass, especially on the 21st day of the experiment and the removal of ligatures from the trachea in experimental animals. Disturbances in the microcirculation of the lung acini were manifested by a sharp increase in blood filling of the microvessels and expansion of their lumen. In this case, the process of erythrocyte penetration into the lumen of the alveoli was sometimes noted. The results of histochemical detection of collagen indicate that in the lung tissue of experimental animals there is no activation of fibrogenetic processes, which would be accompanied by a simultaneous increase in the specific density of collagen. Indicators characterizing the lung tissue (number of cells, their specific density) made it possible to evaluate the corresponding correlations. At the same time, they were not associated with the level of collagen or erythrocyte density in the studied loci of the respiratory system of experimental sexually immature rats. A significant increase in the specific density of erythrocyte mass in lung tissue did not depend on the duration of the experiment. Removal of the ligature and restoration of the tracheal lumen did not significantly affect the restoration of alveolar acini and the spectrum of identified cells. In addition, an increase in the specific density of lung tissue was observed. Conclusion. The findings of this study contribute to deeper understanding of lung damage in children with laryngomalacia and associated respiratory system ventilation impairment. The observed reactive changes in lung connective tissue and collagen synthesis during hypoxia do not necessarily indicate the development of respiratory system fibrosis. However, longer exposure to hypoxic conditions may increase the risk of fibrosis in children.

Aspects of nutriment in maintaining gum wellbeing: A literature review

This is an exhaustive narrative review on nutritional importance regarding periodontium health. Macronutrients have a significant impact on oral health. Highly refined carbohydrate intake has been linked to dental cavities and periodontal diseases. In contrast, complex carbohydrates in whole grains and vegetables promote periodontal health. Proteins are essential for host defences and the synthesis of connective tissues, making them crucial for periodontal well-being. Vegetable proteins positively affect periodontal health. Dietary fats promote inflammation and increase the risk of periodontal disease. Omega-3 fatty acids are well-known for their anti-inflammatory properties and minimizing periodontal inflammation. Vitamins and minerals are essential in maintaining periodontal health. Vitamins A, D, and K are necessary for oral epithelial integrity, bone growth, and tissue maintenance. Ca2+ and Mg2+ deficiencies have been associated with severe periodontal diseases. Antioxidants like vitamin C can mitigate periodontal inflammation. Most dental practitioners acknowledge that a person’s nutritional status attenuates periodontal disorders. The severity of inflammation in the gums is indirectly impacted by the inherent resistance of the periodontal tissues to infection at a systemic level. Dental professionals should address local irritants through different procedures, promote daily plaque control at home, and offer nutritional counselling on improving overall periodontal health.

Scurvy: Rediscovering a Forgotten Disease.

Scurvy is a nutritional deficiency caused by low vitamin C levels that has been described since ancient times. It leads to a varied presentation, affecting multiple organ systems due to its role in the biochemical reactions of connective tissue synthesis. Common manifestations include gingival bleeding, arthralgias, skin discoloration, impaired wound healing, perifollicular hemorrhage, and ecchymoses. Although there has been a dramatic reduction in the prevalence of scurvy in modern times owing to vitamin C supplementation and intake, sporadic cases still occur. In developed countries, it is mainly diagnosed in the elderly and malnourished individuals and is associated with alcoholism, low socio-economic status, and poor dietary habits. Scurvy has been an unusual cause of gastrointestinal (GI) bleeding among other GI manifestations. It can be adequately treated and prevented via vitamin C supplementation.

Human Platelet-Rich Plasma Regulates Canine Mesenchymal Stem Cell Migration through Aquaporins.

Platelet products are commonly used in regenerative medicine due to their effects on the acceleration and promotion of wound healing, reduction of bleeding, synthesis of new connective tissue, and revascularization. Furthermore, a novel approach for the treatment of damaged tissues, following trauma or other pathological damages, is represented by the use of mesenchymal stem cells (MSCs). In dogs, both platelet-rich plasma (PRP) and MSCs have been suggested to be promising options for subacute skin wounds. However, the collection of canine PRP is not always feasible. In this study, we investigated the effect of human PRP (hPRP) on canine MSCs (cMSCs). We isolated cMSCs and observed that hPRP did not modify the expression levels of the primary class of major histocompatibility complex genes. However, hPRP was able to increase cMSC viability and migration by at least 1.5-fold. hPRP treatment enhanced both Aquaporin (AQP) 1 and AQP5 protein levels, and their inhibition by tetraethylammonium chloride led to a reduction of PRP-induced migration of cMSCs. In conclusion, we have provided evidence that hPRP supports cMSC survival and may promote cell migration, at least through AQP activation. Thus, hPRP may be useful in canine tissue regeneration and repair, placing as a promising tool for veterinary therapeutic approaches.

Subclinical Hypertension-Mediated Organ Damage (HMOD) in Hypertension: Atherosclerotic Cardiovascular Disease (ASCVD) and Calcium Score.

Calcium controls numerous events within the vessel wall. Permeability of the endothelium is calcium dependent, as are platelet activation and adhesion, vascular smooth muscle proliferation and migration, and synthesis of fibrous connective tissue. Double-helix computerized tomography is a noninvasive technique that can detect, measure, and compare coronary calcification in the coronary arteries. Despite some convincing evidence about the prognostic value and usefulness of coronary artery calcium score (CACS) in the stratification of cardiovascular risk in the high risk general population and also in hypertensive patients, current guidelines for the management of hypertension, do not include such evaluation among the recommended procedures to be performed in the majority of patients even with the intent to detect hypertension-mediated organ damage (HMOD) in an early phase. On the contrary, the European Society of Cardiology guidelines for the diagnosis and management of chronic coronary syndromes, the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, and the 2018 Cholesterol Clinical Practice Guidelines indicate that the evaluation of CACS may be of some usefulness in specific subpopulations, although this view is not accepted in the US Preventive Services Task Force document. Very recently, the European Society of Cardiology Guidelines on cardiovascular disease prevention in clinical practice stated that CACS estimation may be considered to improve risk classification around treatment decision thresholds. In conclusion, the use of CACS as a diagnostic tool is still controversial. While some evidence exists about is ability to improve stratification of cardiovascular risk in primary prevention, in particular in selected patients who are at intermediate or borderline risk of atherosclerotic cardiovascular disease, there is insufficient evidence to use it as a standard means to assess HMOD.

The Role of Copper Homeostasis in Brain Disease.

In the human body, copper is an important trace element and is a cofactor for several important enzymes involved in energy production, iron metabolism, neuropeptide activation, connective tissue synthesis, and neurotransmitter synthesis. Copper is also necessary for cellular processes, such as the regulation of intracellular signal transduction, catecholamine balance, myelination of neurons, and efficient synaptic transmission in the central nervous system. Copper is naturally present in some foods and is available as a dietary supplement. Only small amounts of copper are typically stored in the body and a large amount of copper is excreted through bile and urine. Given the critical role of copper in a breadth of cellular processes, local concentrations of copper and the cellular distribution of copper transporter proteins in the brain are important to maintain the steady state of the internal environment. The dysfunction of copper metabolism or regulatory pathways results in an imbalance in copper homeostasis in the brain, which can lead to a myriad of acute and chronic pathological effects on neurological function. It suggests a unique mechanism linking copper homeostasis and neuronal activation within the central nervous system. This article explores the relationship between impaired copper homeostasis and neuropathophysiological progress in brain diseases.

Cardiac Complications in Marfan Syndrome: A Review

Marfan syndrome (MFS) is a rare inherited disorder of the connective tissue with an autosomal dominant mode of inheritance which happens as a result of a mutation in the fibrillin-1 (FBN1) gene located on chromosome 15q21.1. This mutation results in the defective formation of microfibrils and increased levels of active transforming growth factor beta (TGFbeta), leading to defective connective tissue synthesis. These changes affect various parts of the body but most notably affected are the heart, eyes, and the musculoskeletal system. The standard presenting features of a person suffering from MFS are tall stature with a large arm span, kyphosis, congenital dislocation of the lens (ectopia lentis) and cardiovascular manifestations. The 2010 modified Ghent criteria are used to diagnose MFS on the basis of parameters such as cardiovascular, eye, and musculoskeletal disorders. The cardiovascular manifestations in a patient with MFS are the leading causes of mortality. The most common and dreaded complication is an aortic aneurysm and subsequent dissection. Cardiomyopathy and arrhythmia are also potential killers in such patients. This article aims to look at the various cardiac complications mentioned above and gain an understanding of their pathogenesis, incidence, and outcome. It also includes a brief overview of the rare complication post-Bentall graft infection, and its cause, diagnosis, and management. Various articles by several different authors from around the world were searched for information regarding the pathogenesis, incidence, and outcomes of these patients and are referenced below.

Progress Toward Understanding Protein Control of Reaction Outcome in the Diverse Reactivity of Iron(II)‐ and 2‐Oxoglutarate‐dependent Oxygenases

In mammals, iron(II)‐ and 2‐oxoglutarate‐dependent (Fe/2OG) dioxygenases have roles in oxygen and body‐mass homeostasis, connective tissue synthesis, and control of transcription and epigenetic inheritance.1 Related enzymes in plants, fungi, and bacteria enable diverse biosynthetic pathways to valuable natural‐product drugs by catalyzing halogenation, epimerization, desaturation, cyclization, ring‐opening/expansion, and endoperoxidation reactions; some of these enzymes even catalyze multiple reaction types within the same pathway!2 Almost every enzyme in this class initiates its reaction by using a common oxoiron(IV) (ferryl) intermediate, first demonstrated by the Penn State group in 2003,3,4 to abstract a hydrogen atom from its target substrate (Figure 1). The iron(II)‐chelating co‐substrate, 2OG, is oxidatively decarboxylated to a succinate ligand in formation of the ferryl complex. To mediate an outcome other than hydroxylation, an enzyme must avoid what can be a facile “oxygen rebound,” Groves term for the coupling of the substrate radical with the iron‐coordinated oxygen just after it abstracts the hydrogen. By direct biophysical observation and “metallomimicry” of intermediates, we have rationalized several of these outcomes in terms of the alternative fates of the substrate radical and the structural features of the enzyme that avert oxygen rebound to enable these alternative fates.5‐11 Very recently, we explained how the most unusual Fe/2OG oxygenase discovered to date, the microbial ethylene‐forming enzyme (EFE), branches from the canonical pathway even before the ferryl intermediate is formed (Figure 2),12,13 leading to global fragmentation of 2OG to three carbon dioxide equivalents and ethylene, a reaction that requires but does not transform the amino acid L‐arginine. The elucidation of the unusual “radical‐polar‐crossover” mechanism of EFE13 significantly expands the paradigm of 2OG‐assisted dioxygen activation pathways and suggests unexpected uses of EFE in biotechnology.1. Hausinger, R. P. Crit. Rev. Biochem. Mol. Biol., 2004, 39, 21–68.2. Bollinger, J. M., Jr., et al. 2015 in RSC Metallobiology Series No. 3. R.P. Hausinger and C.J. Schofield, eds. pp. 95‐122. Royal Society of Chemistry, Washington, D.C.3. Price, J. C., et al. Biochemistry,2003,42,7497‐7508.4. Price, J. C., et al. J. Am. Chem. Soc., 2003, 125, 13008‐13009.5. Matthews, M. L., et al. Proc. Natl. Acad. Sci. USA, 2009, 106, 17723‐17728.6. Chang, W.‐c., et al. Science 2014, 343, 1140‐1143.7. Martinie, R. J., et. al. J. Am. Chem. Soc. 2015,137, 6912‐6919.8. Martinie, R. J., et al. Inorg. Chem. 2017, 56, 13382‐13389.9. Dunham, N. P. et al. J. Am. Chem. Soc. 2018, 140, 7116‐7128.10. Dunham N. P., et al. J. Am. Chem. Soc. 2019, 141, 9964‐9979.11. Pan, J., et al. J. Am. Chem. Soc.2019, 141, 15153−15165.12. Copeland, R. A., et al. J. Am. Chem. Soc. 2021, 143, 2293‐2303.13. Copeland, R. A., et al. Science2021, 373, 1489‐1493.

A Pharmacological Study on the Effect of Calendula officinalis Leaf Extract on Excision Wound Healing in Swiss Albino Mice

Calendula officinalis is one of those plants which have medicinal importance due to its leaf and flowers have pharmacological activity, the important pharmacological parameters have been less investigated properly and can be scientifically proved by reverse pharmacology. It was found of interest to evaluate these properties of the extract of the leaf of C. officinalis. The present study is to screen wound healing activity of gels prepared from methanolic extracts of C. officinalis Linn. using excision wound models in albino mice. Formulations of the extracts were prepared in the gels of Carbopol individually and also in combination in equal ratio. In excision wound models, the so treated animals showed significant reduction in a period of epithelization and wound healing activity. The enhanced wound healing activity of hydroalcoholic extracts may be due to free radical scavenging action and the phytoconstituents present in it which either due to their individual or additive effect fastens the process of wound healing. It was found that Calendula extract enhanced the wound healing activity as seen by increased synthesis of connective tissue, especially collagen. There was a significant increase in the granuloma tissue. The wound contraction and increased tensile strength were found to be statistically significant.

Aligned nanofiber nerve conduits inhibit alpha smooth muscle actin expression and collagen proliferation by suppressing TGF-β1/SMAD signaling in traumatic neuromas.

Transforming growth factor-beta 1 (TGF-β1) is a powerful activator of connective tissue synthesis that is strongly associated with the pathophysiology of traumatic neuroma. Previous studies have demonstrated that aligned nanofiber conduits made from silk fibroin and poly (L-lactic acid-co-ε-caprolactone; PLCL) could prevent traumatic neuromas. In the present study, the possible mechanisms of conduits in treating traumatic neuromas were investigated to provide theoretical basis for procedures. Aligned nanofiber conduits were used for nerve capping. Sciatic nerves of Sprague-Dawley rats were used to create an animal model. The present study contains two parts, each including four experimental groups. SB-431542/SRI-011381 hydrochloride was used to suppress/enhance TGF-β1/SMAD signaling. Part I discussed the connections between traumatic neuroma and the proliferation of alpha smooth muscle actin (α-SMA) and collagen; it also investigated the therapeutic effect of conduits. Part II hypothesized that conduits suppressed TGF-β1/SMAD signaling. Histological characteristics, quantitative analysis of α-SMA, collagens and signaling-related parameters were assessed and compared among groups one month postoperatively. Results from Part I demonstrated that aligned nanofiber conduits suppressed the expression of α-SMA and collagens; and results from Part II revealed the downregulation of pathway-related proteins, suggesting that the suppression was mediated by TGF-β1/SMAD signaling. Aligned nanofiber conduits may be effective nerve capping biomaterials. One of the mechanisms involves suppressing TGF-β1/SMAD signaling. Novel treatments using aligned nanofiber conduits could be developed to manage traumatic neuromas.

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.

The Role of the Liver in Iron Homeostasis and What Goes Wrong?

Iron is an essential mineral that is vital for growth development, normal cellular function, synthesis of hormones and connective tissue, and most importantly, serves as a component of hemoglobin to carry oxygen to body tissues. The body finely regulates the amount of circulating and stored iron within the body to maintain concentration levels within range for optimal physiologic function. Without iron, the ability for cells to participate in electron transport and energy metabolism decreases. Furthermore, hemoglobin synthesis is altered, which leads to anemia and decreased oxygen delivery to tissue. Problems arise when there is too little or too much iron. This review explores the role of the liver in iron physiology, iron overload and discusses the most common causes of primary and secondary hepatic iron overload.

Advances in molecular mechanisms of pelvic organ prolapse (Review).

Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directly caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed.

Molecular factors associated with regression of liver fibrosis of alcoholic etiology

Liver fibrosis develops as a result of chronic liver damage of various etiologies, is characterized by excessive synthesis of connective tissue by activated stellate liver cells. The toxic effect of alcohol is one of the most significant and common etiological factors worldwide. Stellate cell activation results from the interaction of multiple molecular fibrogenic pathways triggered by intracellular and extracellular, hepatic and extrahepatic stimuli. Data analysis showed that knowledge about these abnormal pathways and biomolecular processes may further contribute to the improvement of approaches to assessment of disease prognosis and treatment of alcoholic liver disease.

Effects of Adipose-Derived Stem Cells and Platelet-Rich Plasma for Prevention of Alopecia and Other Skin Complications of Radiotherapy.

Radiotherapy (RT) involves the use of ionizing radiation in treating malignancies and benign disorders. However, RT damages target and healthy surrounding tissues in a dose-dependent manner. This effectively reduces patient compliance and quality of life, thereby warranting the prevention of RT-induced adverse effects on skin. Adipose-derived stem cells (ASCs) are used to treat RT-induced damage and platelet-rich plasma (PRP) provides a scaffold that potentiates the effects of ASCs. Thus, the aim of this study was to determine the mechanism employed by ASCs and PRP in protecting against RT-induced adverse effects. We have established an immunodeficient mouse transplantation model using which human hair follicular units were implanted. When the follicular units were macroscopically and microscopically mature and anagenic, we administered localized RT. Subsequently, the mice were randomly divided into 4 groups based on the subcutaneous injection of the following to the irradiated transplantation site: saline, PRP, ASCs, and a combination of ASCs and PRP. Next, we used macroscopic and microscopic analyses to determine the protective effects of the injected solutions on skin and hair follicles. Adipose-derived stem cells reduced RT-induced adverse effects, such as impaired wound healing, alopecia, skin atrophy, and fibrosis by suppressing inflammation, dystrophy, degeneration, connective tissue synthesis, and apoptosis and increasing cellular proliferation, differentiation, and signaling. Moreover, these effects were augmented by PRP. Thus, co-administering ASCs with PRP in mice prevented RT-induced adverse effects and can be tested for use in clinical practice.

MODERN VIEW ON THE PROBLEM OF DIAGNOSIS AND TREATMENT OF THE GENITOURINARY SYNDROME

The article highlights the current approach on the problem of genitourinary syndrome (GS) diagnosis and treatment in the perimenopausal period patients. Recent studies indicate a significant role of undifferentiated connective tissue dysplasia (UDCTD), which is manifested by a violation of the collagen and the main matrix of connective tissue structure (CT). Nowadays, there is no unified approach on the GS diagnosis and treatment in perimenopausal period women, which determined the purpose and objectives of our research.The purpose of the research: pathogenetically justify CO2 -laser application in the complex treatment of genitourinary syndrome in perimenopausal period patients.Materials and methods of research. We examined 132 women aged 45-55 years with clinical manifestations of GS, who, depending on the proposed therapy, were divided into the main group – 56 women and the comparison group – 76 women. In addition to the General clinical examination patients of the both groups were examined for the contents of CT markers of synthesis (Total P1 NP, P3 NP, Total) and resorption (deoxypiridinolin Pyriliks – D). In order to determine the severity of GS symptoms and to identify sexual dysfunction index we used PFDI-20 and FSFI questionnaires. Women of the main group received therapy that involved the application of 4 sessions of CO2 - laser at an interval of 30-45 days in combination with local application of estradiol-based cream for 7 months. Women of the comparison group received only therapy involving local application of estradiol-based cream for 7 months.The results of the study and their discussion. The average age of patients in the examined groups was 47,3±2,4 years. For women with GS manifestations, the average value of the type I collagen synthesis marker was decreased by 58,5% (the main group) and by 65,2% (the comparison group) from the physiological norm. At the same time, the average value of the marker of III type collagen synthesis in women of the study groups was increased by 52,2% (the main group) and by 36,0% (the comparison group) from the physiological norm. The average value of the connective tissue resorption marker Pyriliks-D in women of the main and the comparison groups, did not differ significantly. According to the PFDI-20 questionnaire, there was a significant decrease in the median score from 55 to 18 in women of the main group during 8 months of treatment. According to FSFI questionnaire, a significant increase in the index of sexual function in women of the main group (the median score before treatment was 25, after treatment – 46; p<0,05) was noticed. Determination of the average Total P1 NP marker concentration in the dynamics of treatment after 4 months demonstrated a significant increase by 72,8% in women who received CO2 -laser therapy in combination with local estradiol treatment. The average Total P3 NP marker concentration in women who received CO2 -laser therapy in combination with local treatment significantly decreased compared to the base value by 62,4%. Against the background of CO2 -laser therapy in combination with local estradiol treatment in women of the main group and the comparison group, there was no significant difference in the indicators of the connective tissue resorption marker Pyriliks-D.Conclusions. The inclusion of CO2 -laser therapy to the complex treatment of genitourinary syndrome can significantly reduce the manifestations of genitourinary disorders, which is confirmed by a significant decrease in the median score from 55 to 18 in women of the main group according to the results of PFDI-20 questionnaire (p<0,05). The positive therapeutic result of the CO2 -laser, from our point of view, occurs due to the effect on the etiopathogenetic mechanisms of the syndrome complex – an age-related imbalance of markers of synthesis and resorption of connective tissue. An increase in the concentration of I type collagen synthesis marker contributed to a synergistic decrease in the concentration of III type Total P3 NP marker in women of the main group and stabilization of its value in the dynamics of treatment. From our point of view, a study of the hormonal status of women with genitourinary syndrome to improve the tactics of etiotropic treatment and prevention of relapse, offers the greatest promise.

Role of sex steroid hormones in pelvic organ prolapse.

Pelvic organ prolapse (POP) affects a significant percentage of women and contributes to major healthcare costs both in the United States and worldwide. This review examines the current understanding of the role of sex steroid hormones (estrogens, androgens, and progesterone) in POP in premenopausal, perimenopausal, and postmenopausal women. We reviewed the relevant studies on POP related to estrogens, androgens, and progesterone in both animal models and humans. Estrogen has a profound influence on the synthesis and metabolism of pelvic connective tissues, and may have the ability to both prevent POP and improve prognosis if used therapeutically. There is limited research regarding the role of androgens and progesterone and their receptors in POP and results so far have been contradictory, warranting further study to determine whether changes in androgen and progesterone receptor expression are a cause or effect of POP. Because of the role that estrogen plays in maintaining the integrity of pelvic floor connective tissues, we propose that rigorous and well-controlled studies are needed on the role of exogenous estrogen administration as a form of POP prevention. : Video Summary:http://links.lww.com/MENO/A583.

Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans.

Traumatic strain injury in skeletal muscle is often associated with fluid accumulation at the site of rupture, but the role of this injury exudate (EX) in cellular responses and healing is unknown. We aimed to characterize the EX sampled from human hamstring or calf muscles following a strain injury (n = 12). The cytokine and growth-factor profile, gene expression, and transcriptome analysis of EX-derived cells were compared with blood taken simultaneously from the same individuals. Cellular responses to the EX were tested in 3-dimensional (3D) culture based on primary human fibroblasts and myoblasts isolated from hamstring muscles. The EX contained a highly proinflammatory profile with a substantial expression of angiogenic factors. The proinflammatory profile was present in samples taken early postinjury and in samples aspirated several weeks postinjury, suggesting persistent inflammation. Cells derived from the EX demonstrated an increased expression of fibrogenic, adipogenic, and angiogenesis-related genes in comparison with blood cells. The injury EX stimulated fibroblast proliferation 2-fold compared with plasma, whereas such an effect was not seen for myoblasts. Finally, in 3D cell culture, the EX induced an up-regulation of connective tissue-related genes. In summary, EX formation following a muscle-strain injury stimulates fibroblast proliferation and the synthesis of connective tissue in fibroblasts. This suggests that the EX promotes an acute tissue-healing response but potentially also contributes to the formation of fibrotic tissue in the later phases of tissue repair.-Bayer, M. L., Bang, L., Hoegberget-Kalisz, M., Svensson, R. B., Olesen, J. L., Karlsson, M. M., Schjerling, P., Hellsten, Y., Hoier, B., Magnusson, S. P., Kjaer, M. Muscle-strain injury exudate favors acute tissue healing and prolonged connective tissue formation in humans.

ОСОБЛИВОСТІ ОБМІНУ КОЛАГЕНУ У ЖІНОК ПРЕМЕНОПАУЗАЛЬНОГО ВІКУ З СТРЕСОВИМ НЕТРИМАННЯМ СЕЧІ НА ТЛІ КОНСЕРВАТИВНОГО ТА ЛАЗЕРНОГО ЛІКУВАННЯ

Стаття узагальнює аргументи та контраргументи в межах наукової дискусії з питання впливу недиференційованої дисплазії сполучної тканини на розвиток стресового нетримання сечі у жінок пременопаузального віку та підходи до лікування даної патології. Основною метою проведеного дослідження є визначення особливостей обміну колагену у жінок пременопаузального віку зі стресовим нетриманням сечі для удосконалення тактики лікування та розробки диференціального підходу до профілактики розвитку даної патології в майбутньому. Систематизація даних літературних джерел та відсутність єдиного підходу до лікування стресового нетримання сечі у жінок пременопаузального віку засвідчила необхідність пошуку нових підходів до лікування даного захворювання, які впливатимуть на етіопатогенетичні ланки виникнення стресового нетримання сечі у даної категорії гінекологічних пацієнток. Актуальність дослідження даної патології полягає у тому, що стресове нетримання сечі – це проблема, яка суттєво знижує якість життя жінок в пременопаузі, стає причиною замкненості та невпевненості в собі, а в певних випадках може призводити й до психологічних порушень. Методика проведення дослідження полягала в проспективному клініко-статистичному обстеженні, до якого було залучено 133 пацієнтки пременопаузального віку зі стресовим нетриманням сечі, яких в залежності від призначеної терапії було розподілено на дві групи. До основної групи увійшли 57 жінок зі стресовим нетриманням сечі пременопаузального віку, яким з метою корекції проявів захворювання була запропонована лазерна терапія. Групу порівняння сформували 76 пацієнток пременопаузального віку зі стресовим нетриманням сечі, які отримували консервативне лікування. Всім пацієнткам обстежених груп, крім загально-клінічного обстеження, проводилось визначення маркерів синтезу (Total P1NP, Total P3NP) та резорбції (дезоксипіридинолін Pyriliks – D) сполучної тканини на початковому рівні, одразу після лікування та через 6 місяців лікування, тривалість дослідження становила десять місяців. Результати клінічного дослідження продемонстрували, що у даної категорії пацієнток на тлі застосування лазерної терапії відмітився достовірно-позитивний ефект, отриманий в результаті лікування, спрямованого на підвищення середнього рівня маркеру синтезу колагену I типу та зниження середнього рівня маркеру синтезу колагену III типу, а також нормалізації середнього рівня маркера резорбції сполучної тканини. Дослідження емпірично підтверджує та теоретично доводить, що використання лазерної терапії є патогенетично-обумовленим, адже його позитивний ефект реалізується шляхом впливу на сполучну тканину сечо-статевої діафрагми, стимуляцію вироблення колагену І типу та синергічне пригнічення продукції колагену ІІІ типу та Pyriliks-D. Результати проведеного дослідження можуть бути корисними для лікарів гінекологічних стаціонарів, лікарів загальної практики і сімейної медицини та лікарів жіночих консультацій.

A pharmacological study on the effect of calendula officinalis extract on wound healing in animals

Background: Calendula officinalis is one of those plants which have medicinal importance due to its flowers (HECO) has pharmacological activity the important pharmacological parameters have been less investigated properly and can be scientifically proved by reverse pharmacology. It was found of interest to evaluate these properties of extract of flowers of Calendula officinalis.Methods: Study was conducted in Albino Wistar rats. For evaluating wound healing activity Excision wound model and Incision wound mode were used containing 4 groups each. The wound contraction was studied by tracing the raw wound area on graph paper. Scar area and time for complete epithelisation were measured. The percentage of wound contraction was recorded. The differences between experimental groups were compared by ANOVA followed by Students “t” unpaired test.Results: In the excision wound healing model, 5% and 10% flowers showed a highly significant reduction in wound area as compared with control. In incision wound model, rats treated with 5% and 10% ointment of Calendula officinalis flowers extract showed highly significant increase in tensile strength as compared to control.Conclusions: It was found that the Calendula extract enhanced the wound healing in both the models as seen by increased synthesis of connective tissue especially collagen. There was a significant increase in the granuloma tissue. In both the models wound contraction and increased tensile strength was found to be statistically significant.