Understanding of cellular and tissue mechanisms which are the cornerstone of age changes of connective tissue allows to create at students of the first courses idea of realization of trophic, mechanical, protective, adaptive functions during various age periods and to create complete approach to assessment of integrative connective tissue of function during various age periods. In work cytotopographical classification of connective tissue proper is provided, characteristic of a cytogenesis and cytophysiology of cells of a fibroblastic differon in age aspect is given, are provided a morph – functional changes of connective tissue in the prenatal and post-natal periods of an ontogenesis. Special attention is devoted to morphogenetic changes of cells of a fibroblastic differon and intercellular matrix of fibrous connective tissue when aging. Age changes of connective tissue are defined by reduction of number and change of a ratio between cell of a fibroblastic differon, decrease in their proliferative and synthetic activity that is followed by changes of quantitative and qualitative structure of an intercellular matrix and it integrative – buffer properties.

At the present stage, the subject of intensive research is the study of the transmission mechanisms of molecular signals of the conserved Notch signaling pathway in the development of liver pathologies. The review article summarizes current scientific evidence on the role of the signaling pathway in liver fibrogenesis. Literature analysis indicates that the role of the Notch signaling pathway in the regulation of stellate cells and hepatocytes activation, macrophage polarization and its interaction with other signaling pathways in fibrogenesis has not been fully studied. It should be noted that the study of changes in the activity of the signaling cascade is of great therapeutic importance in the development of a medical guidelines for fibrosis using new antifibrotic medications.

Background. There are many strategies for modifying the surface of implants to create optimal conditions for the development of bone tissue. At the same time, the question of correlation of the effect of surface roughness or surface chemical composition on cell activity or osteogenesis processes remains open. Objective. The study of cellular mechanisms of osseointegration using cell cultures that occur after implantation of implants with a different type of alloy and the nature of their surface. Methods. To analyze the adhesion and cell proliferaiton, the resazurin reduction method was used, scanning electron microscopy was used to determine the distribution of cells on the sample surface and the type of cell interaction with surface. Results. Cell adhesion is observed in all studied groups, and the degree of cell adhesion is directly related to the presence of hydroxyapatite on the surface. A growing trend in the proliferation of osteoblasts is noted, while fibroblast proliferation slows down from the 3rd to the 7th day. At the same time, slow cell proliferation occurs on the surface of the implants without modification, and the percentage the reduction of resazurin does not exceed 23.5%. It should be noted that there is no difference between the types of alloys, which proves the predominance of the influence of surface topography on the proliferative activity of osteoblasts. Scanning electron microscopy on the 7th day revealed the presence of osteoblasts and fibroblasts in all studied samples. However, in the absence of hydroxyapatite, the cells are unevenly located on the surface of the sample, they are large in size and have long processes that do not have a clear orientation, and on the surface with hydroxyapatite coating there is a higher cell growth density, which predominantly has 2 processes and oriented in the same direction. Conclusion. The use of hydroxyapatite coating significantly increases the ability of cells to adhere to the surface of the implant. The presence of calcium and phosphorus mainly stimulates the proliferation of osteoblastic dipheron cells and almost does not affect the ability of fibroblasts to proliferate.

Актуальність. Солі важких металів негативно впливають на здоров'я населення та викликають розвиток патології окремих органів тасистем організму.Наднирники займають одне з ключових місць у регуляції та підтриманні основних функцій організму. Мета. Вивчення морфологічних адаптивних перебудов структурних компонентів кори наднирників статевозрілих щурів-самців за умов довготривалого впливу солей важких металів та негормональної корекції вітаміном Е залишається актуальною та недостатньо вивченою темою. Методи дослідження. Експеримент проведений на 24 білих статевозрілих щурах-самцях масою 200-250г, віком 5-6 місяців, які після довготривалого (90-денного) впливу комбінації солей важких металів: цинку (ZnSO4 · 7H2O) – 5 мг/л, міді (CuSO4·5H2O) – 1 мг/л, заліза (FeSO4) – 10 мг/л, марганця (MnSO4·5H2O) – 0,1 мг/л, свинця (Pb(NO3)2) – 0,1 мг/л та хрому (K2Cr2O7) – 0,1 мг/л на протязі 30-ти діб вживали звичайну питну воду з препаратом-коректором вітаміном Е (9,1 мг / кг 10% перорального масляного розчину). Застосовувалися загальноприйняті гістологічні методи дослідження. Результати. Антиоксидант L-токоферол, після надходження до організму комбінації солей важких металів, виявив достовірну стреспротекторну дію на всі структурні компоненти наднирника: стан судинної стінки, ядерного та секреторного апарату спонгіоцитів всіх зон кори. Підсумок. L-токоферол сприяє зменшенню токсичного впливу солей важких металів на кору наднирників, виявляє мембранопротекторну та стреспротекторну дію, послаблює прояви стадії виснаження загального адаптаційного синдрому, частково відновлює гормональну активність адренокортикоцитів. Але, 30-ти добовий термін корекції морфологічних перебудов, викликаних надходженням до організму солей важких металів, є недостатнім для повного відновлення стану судинної стінки, реологічних властивостей крові та секреторної активності клітин кори наднирника.

Background. Extramammary Paget’s disease is one of the rarest malignant skin tumors which are mostly apocrine. However, there were described some cases in non-apocrine bearing glands areas. The perianal region, as part of the anogenital site, is the place where extramammary Paget’s disease could manifest. It is used to classified this disease into 2 categories: primary and secondary, where the main differentiating feature is the absence or presence of underlying carcinoma relatively. Due to extramammary Paget’s disease rarity all around the world publishing information about any case could help to evaluate the situation in all. Objective. To report a rare case of the extramammary Paget’s disease and analyze one-case-publications during last 5 years on PubMed and assessed contributions of age, sex, and localizations. Methods. While making a diagnosis histological, immunohistochemical studies and statistical methods were used. Results. The first case of primary noninvasive extramammary Paget’s disease was diagnosed in the immunohistochemical laboratory of the Medical Diagnostic Center of the Medical Academy and described in this article. A 64-year-old Ukranian man suffered within 1 year from big erythematous pruritus unhealed lesion between his buttocks and came to our laboratory to verify suspicious malignant melanoma what was assumed while previous histological study. According to immunohistochemical study, this tumor had positive status with cytokeratin 7, HER-2/Neu, EGFR and p16, while cytokeratin HMW, S100, HMB-45, EBV were negative. Such immunophenotype might point to some ways of the pathogenesis of this problem. The theory about involved Toker cell and preceded Toker cell hyperplasia had both advantages and drawbacks, what we showed with the presented example. There were already published 49 cases with middle age 67,68±1,64; median 67 years, m:f ratio 1,58:1 and utterly predominant location – anogenital region. Conclusion. Received data have mostly corresponded to published information previously.Both clinical studies and immunophenotype gave a possibility to make an accurate diagnose.

Background. Testicular tumors are rare neoplasia (1-2% of all malignant tumors in men) and are more common in young men, what attaches importanceof this problem both medical and social significance. Objective. The aim of the work was to study proliferative and apoptotic processes in testicular seminoma. Methods. The study was performed on 13 surgically removed testicles affected by seminoma.Tumors were grouped according to the degree of tumorous progression in accordance with the pTNM classification. For evaluation of proliferative and apoptotic processes the relative area (S) and intensity (L) of Ki-67, Bax, Bcl-2, and p53 expression were studied. The proliferation index (PI) was calculated as well. Results. The study determined increasing of average S, L values of Ki-67 expression and PI, and also very high and moderate positive correlation between PI and S with L expression (r= +0,98; r= +0,60; p<0,05, respectively) during the transition from the initial to the late stages of tumorous progressionwas revealed. S of Bax expression was also increasing at the transition from early to late stages of tumorous progression, and L expression remained high regardless of stage. High positive correlation between S of Bax and S of Ki-67 expression and between S of Bax and PI (r= +0.83; r= +0.84; p<0.05, respectively) was revealed during the transition from the initial to the late stages of tumorous progression. This result allows us to talk about the lack of resistance of seminoma tumorous cells to apoptosis. The activity of the anti-apoptotic protein bcl-2 in the seminoma was extremely insignificant, and p53 expression was absent, which together indicates a low tumor aggressiveness. Conclusion. Based on the foregoing we believe that in the diagnosis of testicular tumors it is appropriate to use Ki-67, Bax, bcl-2 and p53, as reflecting the malignant potential of the tumor and as prognostic markers. In the same time we have opinion that increasing of S of Bax expression during the transition from the initial to the late stages of tumorous progression in combination with p53 intactness characterizes seminoma as curable tumor with lowaggressiveness.

Background. With the development and improvement of modern methods of immunohistochemical examination, new possibilities for studying the molecular-biological features of cervical dysplasia (CD/CIN) emerged, opening new stages of its morphogenesis. Taking into account the demographic situation in Ukraine, and the fact that incidence rate of squamous cell intraepithelial cervical lesions and infertility have a tendency to increase, it becomes apparent the need for further investigation of CIN associated with the (HPV) infection. Objective. The purpose of the study was to determine the immunohistochemical features of cervical dysplasia in women with infertility, depending on the progression of papillomavirus infection. Methods. Specific quantitative diagnostics of real-time polymerase-chain reaction with hybridization-fluorescence detection was used to detect papillomavirus infection. Immunohistochemical studies used primary monoclonal antibodies to Ki-67, p63, VEGF, p16ink4a, estrogen (ER) and progesterone receptors (PR), E-cadherin. The results obtained during the study were subjected to statistical processing by methods of variational statistics. Results. Immunomorphological features of cervical dysplasia depending on the progression of papillomavirus infection have been established in women with infertility, and the reliable influence of HPV WRC loading on the level of expression of molecular-biological markers depending on the severity of cervical dysplasia has been demonstrated. Conclusion.Therefore, the use of Ki-67, p63, pl6ink4a, VEGF, E-cadherin markers is the most optimal for the implementation of the diagnostic process and for determining the course of CIN, since the change in their expression most often corresponded to the severity of CIN.

Backgroud. The metabolic syndrome of the mother and the effect of its components on the fetal development is the focus of medical science and health care. Also known that it is the close relationship between functional immaturity of the organs and tissues of the fetus and comorbidities of the mother, especially type 2 diabetes, hypertension, obesity and dyslipidemia. Objective is to carry out differential diagnosis of pathomorphological changes in the lungs of premature infants in the study groups. Methods. The studies were performed on the section material of the lungs of premature infants of 29-33 weeks of gestation (120 cases), which were divided into three groups depending on the components of the metabolic syndrome of the mother. Results. Moderate swelling of the mucous membrane, areas of blood filling, venous plethora, mucous membrane in segmental bronchial tubes of children of group I are observed. Segmental bronchi of children of group II corrugated and swollen, hyperplastic growths of the ciliated prismatic epithelium are observed. In group III of the study, the mucous membrane of the segmental bronchi is represented by a multilayered ciliated cylindrical epithelium; Morphometric parameters of the epithelial cells of the respiratory parts of the lungs of premature infants in the three study groups indicate a lag in their differentiation processes, which delay the structural and functional development of lung tissue. Conclusion. Differential diagnostics of pathomorphological changes in the lungs of premature infants in the study groups revealed immaturity of the lung tissue, which corresponds to the specified gestation periods, and their morphological changes are related to the influence of maternal factors, such as hypertension, diabetes mellitus, diabetes mellitus.

Background. The study of normal embryonic development of the vertebral column is important for understanding the pathogenesis of congenital anomalies of the axial skeleton. Objective. To study the histodifferentiation of cartilage and bone tissue in the vertebral centra and neural arches of particular parts of the vertebral column in human embryos of the first half of fetal development. Methods. Whole-mount skeletal preparations, stained with alcian blue and alizarin red, as well as serial histological sections from the embryological collections of the Belarusian State Medical University and from the Carnegie collection (3D Atlas of Human Embryology project, https://www.ehd.org/virtual-human-embryo/ ) using hematoxylin and eosin and Masson's trichrome staining were studied. A total of 37 human embryos/fetuses from 5 to 20 weeks of age were used. Results. Primary centers of ossification were found in the neural arches of the upper cervical and centra of lower thoracic and upper lumbar vertebrae of 9-10-week human embryos. They consist of hypertrophic chondrocytes surrounded by a mineralized matrix. Complete ossification of the cartilaginous anlages of the vertebral bodies begins at 12 week of embryogenesis. The appearance of the osteoid and structural elements of the bone marrow in their centers is preceded by the ingrowth of vascular canаls. In the vertebral neural arches, the formation of bone tissue occurs due to endochondral and perichondral ossification. Three growth zones are formed near the ossification center – one is for the region of the pedicle of the neural arch; the other for the lamina/spinous process; the third – for the base of the transverse process. Conclusion. According to the histological structure, the ossification of the vertebral body is similar to the secondary ossification center of long bone, and the ossification center in the neural arch at the microscopic level resembles the diaphyseal ossification center of the long bone. Differences in the timing of appearance and osteogenic pathways of the vertebral centra and neural arches are determined by different sources of their origin.

Background. One of actual problems in medical practice are diseases of the urinary system and the bladder in particular (20%). Many diseases of the urinary system in older children and adults occur in the neonatal period or even before birth. Objective.The aim of this study was to study the morphological features of the bladder of rats in the period of early postnatal ontogenesis.Methods. Study consisted of a histological examination of the bladders of 24 rats and the mathematical processing of data. The containment and manipulations on animals were in accordance with the “General ethical principles of experiments on animals.” A morphometric study and photomicrography were performed using a ZEIZZ microscope with an Axiocam 105 color digital microplotter. Variation statistical methods were used to using perform a quantitative analysis of the results of a morphometric study by using programs such as Excel and STATISTICA. Results. Next properties were studied: the average length and thickness of the folds of the mucous membrane, the thickness of the urothelia and its own plate, muscle shell and outer shell. The average number of lymphocyte cells in the field of view. An increase in the thickness of the membranes of the bladder was observed, with a maximum thickness being reached by the 30th day of life. Also, by the end of the first month, an increase in the quantitative and qualitative composition of cells of the immunomorphological complex in the mucous structure is well pronounced. This can be attributed to a change in the type of nutrition of the rats, since from 14 to 21 days there is a transition from dairy to natural nutrition.