Pancreatic stellate cells: the top managers of the pancreatic tumor microenvironment.

Background Stellate pancreatocytes, being cells - producers of stromal components, actively interact with cancer cells, determine the formation of a stromal barrier between the latter and thereby provide tumor chemoresistance. Objective The review is devoted to the analysis of recent data on the role of stellate pancreatocytes in the formation of the stromal microenvironment of pancreatic tumors, molecular mechanisms through which the regulation and realization of stellate cell functions is carried out. Methods Data processing was carried out by the method of complex material analysis. Results. Stellate pancreatocytes (PSC) exhibit phenotypically and functionally two states: inactive and active. PSC activation is carried out by cells of the developing tumor through a variety of molecular mediators. Activation triggers for PSC are Yes-associated protein, TGF-β1, miRNA let-7d, IL-8, MCP1, TGF-β2, IGFBP2, and others. 10 actively expressed genes were identified: TP53, SRC, IL6, JUN, ISG15, CAD, STAT1, OAS3, OAS1, VIM during co-cultivation of a cancer cell line (PCC) with PSC. PSC deactivation is associated with speckle-type mediator POZ (SPOP) acting through nuclear factor-kappaB, transretinoic acid (ATRA). Exhibiting their activity, PSCs express several stem cell markers, α-SMA (α-actin of smooth muscle cells), vimentin, α ITGA 11 (collagen type I receptor), α5 integrin receptor ITGA5 (fibronectin receptor), hyaluronic acid, hyaluronan synthase 2 (HAS2), hyaluronidase 1 (HYAL1), BAG3 , matrix metallopeptidase 2 (MMP2), Nodal protein, miR-1246 and miR-1290, miR-210, CCN2 (connective tissue growth factor), TRPV1, SP and CGRP (Calcitonin gene-related peptide) and many other factors. Сonclusion. Stellate pancreatocytes, being producers of the interacinar stroma, are activated by various factors (TNF-α, IL-6, MCP-1, ATP, and HMGB1, etc.), including factors produced by tumor cells of the pancreas, and act as regulators of proliferation, migration, and suppression apoptosis of the latter. An increase in the expression of α ITGA 11 (type I collagen receptor), α5 integrin receptor ITGA5 (fibronectin receptor), metallopeptidases, Nodal protein, miR-1246, miR-1290, and miR-210 is observed in tumor tissue, that indicates the activation of these cells. The maintenance of the active state of PSC is provided by tumor cells, for which stellate pancreatocytes are partners in the progression of the neoplastic process. Further study of the mechanisms of interaction in the PSC-tumor cell system creates the prospect of revealing levers of influence on the pathogenesis of pancreatic tumors.

To the anniversary of Professor Antonina Mykhailivna Yashchenko

3 1 січня виповнилося 75 років від дня народження та 38 років наукової та педагогічної діяльності доктора медичних наук Ященко Антоніни Михайлівни, професора кафедри гістології, цитології та ембріології Львівського національного медичного університету ім. Данила Галицького. У 1964 році закінчила Львівське медичне училище №1. У 1965 році вона вступає до Львівського державного університету ім. Івана Франка на біологічний факультет. Ще у студентські роки під час виконання курсових і дипломних робіт проводила наукові дослідження з використанням гістологічних методів. Після закінчення університету працювала у лабораторії експрес-діагностики реанімаційного відділення клінічної лікарні Львівської залізниці. У цей час з’явилися перші наукові публікації, що стосувалися дослідження підшлункової залози при панкреатитах. 1982 року Антоніна Михайлівна була обрана за конкурсом на посаду асистента кафедри гістології, цитології та ембріології ЛНМУ. У 1986 році захистила кандидатську дисертацію «Гистофизиология подчелюстных слюнных желез потомства при нарушении баланса тиреоидных гормонов материнского организма», у якій вперше були описані процеси розвитку підщелепних слинних залоз потомства за умов гіпотирозу материнського організму, показаний процес становлення їх ендокринної функції. Визначну роль у науковому житті ювелярки відіграла ерудована і цікава особистість – професор Є.С. Детюк, під керівництвом якої була виконана і захищена дисертація. Після обрання у 1992 році на посаду доцента кафедри гістології, цитології та ембріології Антоніна Михайлівна активно включилася у навчально-методичну роботу кафедри: за її авторства опублікована низка методичних рекомендацій для студентів медичного та стоматологічного факультетів. У 1998 році за її співавторства вийшов друком навчально-методичний посібник для студентів стоматологічного факультету «Атлас мікроанатомії органів ротової порожнини», до складу якого увійшли фрагменти її власних наукових досліджень і який у 1999 році був відзначений нагородою Ярослава Мудрого Академії наукН вищої школи України. У 2004 році Антоніна Михайлівна захистила докторську дисертацію «Лектини як маркери в нормі і патології», у якій відображено можливості використання методів лектиногістохімії у процесах диференціації клітин та діагностиці патологічних процесів. Основним науковим напрямком Антоніни Михайлівни є вивчення вуглеводних детермінант як сигнальних молекул у процесах міжклітинної взаємодії, диференціації та проліферації клітин органів травної, ендокринної, репродуктивної систем експериментальних тварин та людини у процесі онтогенезу, порівняльно-видовому аспекті та патологічних процесах. Результатом наукових пошуків Антоніни Михайлівни стали наукові статті, кількість яких понад 250, у тому числі 2 авторських свідоцтва на винаходи. Під її керівництвом захищено 9 кандидатських дисертації. Професор А.М.Ященко – співавтор Національних підручників з гістології, цитології та ембріології для студентів медичного (2018 р.) і стоматологічного (2020 р.) факультетів. Професор Ященко А.М. читає лекції на медичному та стоматологічному факультетах університету. Її лекції базуються на принципах проблемного навчання, носять інтерактивний характер, збагачені новими фактами молекулярної біології, біохімії, генетики та клінічної морфології. Антоніна Михайлівна виступала з науковими доповідями на конгресах та конференціях, які проводилися в Україні та за її межами. Блискучий лектор, Антоніна Михайлівна вміє захопити студентів та залучити їх до наукового пошуку. Створений під її керівництвом науковий студентський гурток є гордістю кафедри. Серія наукових студентських робіт, які проводились під її керівництвом з використанням методів лектиногістохімії відзначені нагородою Національної академії медичних наук України. За її участю виконувались фрагменти наукових робіт присвячених дослідженню органів і тканин з використанням методів лектиногістохімії не тільки суміжних кафедр університету, а й інших вузів України та близького зарубіжжя. Значну консультативну допомогу професор А.М. Ященко надавала при виконанні багатьох кандидатських та докторських дисертацій. Високий науковий рівень Ювілярки, організаторські здібності, активна життєва позиція, творчий науковий підхід у вирішенні поставлених завдань, доброзичливість та вимогливість до себе визначають високий авторитет та повагу серед викладачів, співробітників та студентів університету.

Morphological characteristic of premature infants’s kidneys with opened Ductus Arteriosis (by the autopsy).

Background. Kidney has protracted nephrogenesis and depend on hemodynamic changes on the highest level in support of natural transition to extrauterine circulation. Fetal communications like Ductus Arteriosus take part in the shunting from the aorta to the pulmonary artery. Increase of this shunting of the blood leads to hyperperfusion with hypoxic changes of some development systems of organs with protracted morphogenesis so like kidneys. Objective. To determine the features of postnatal morphogenesis of the kidneys in premature infants with a gestational age of 25 to 35 weeks on the background of an open ductus arteriosus. Methods. 21 autopsy material premature infant’s kidney which were fixed by 10%-formalin and then were subjected to the standard histological procedures. Slides were stained by hematoxylin and eosin. We used the complex of histological and morphometric methods. There were created 3-demenshional models of kidney’s fragments. We carried out biometrical and statistical analysis. Results. During our research it was determines that the changes of the volume of the functional parenchyma of the kidney and the diameter of the Ductus Arteriosus became in inverse relationship. The wider the duct the smaller the volume of the functional parenchyma because of atrophic and necrotic changes during the late stages of glomerulo- and tubulogenesis. These changes could be distinguished by the quantitative density of development on three germinate layers of the cortex of kidney. Сonclusion. Summing up, it determined the retardation of glomerulogenesis particularly superficial area of the cortex because of the opened Ductus Arteriosus.

William K. Ovalle PhD, Patrick C. Nahirney PhD Netter's Essential Histology: With Correlated Histopathology (Netter Basic Science) 3rd Edition

With strong correlations between gross anatomy and the microanatomy of structures, Netter’s Essential Histology, 3rd Edition, is the perfect text for today’s evolving medical education. Concise and easy to use, it integrates gross anatomy and embryology with classic histology slides and state-of-the-art scanning electron microscopy, offering a clear, visual understanding of this complex subject. Additional histopathology images, more clinical boxes, and new histopathology content ensure that this textbook-atlas clearly presents the most indispensable histologic concepts and their clinical relevance.Helps you recognize both normal and diseased structures at the microscopic level with the aid of succinct explanatory text as well as numerous clinical boxes. Features more histopathology content and additional clinical boxes to increase your knowledge of pathophysiology and clinical relevance. Includes high-quality light and electron micrographs, including enhanced and colorized electron micrographs that show ultra-structures in 3D, side by side with classic Netter illustrations that link your knowledge of anatomy and cell biology to what is seen in the micrographs. Provides online access to author-narrated video overviews of each chapter, plus Zoomify images and Virtual Slides that include histopathology and can be viewed at different magnifications.

Analysis of the malignant ovarian tumors incidence in the Sumy region in 2014-2018.

Background. Ovarian cancer is a very important pathology of the female reproductive system and tends to increase in incidence and mortality rates around the world. Despite the fact that ovarian cancer prevalence is lower than that of breast and cervical cancer, its mortality rate is three times higher. Aim. To analyze the incidence of ovarian cancer in the female population of Ukraine and the Sumy region in 2014–2018. Methods. Data from the National Cancer Register of Ukraine were used for this work. A statistical analysis of the incidence rates of ovarian cancer in the population of Ukraine and Sumy region was carried out. Results. The highest incidence of ovarian cancer in the Sumy region was detected in 2018 (12.5 cases per 100,000 women), and the lowest - in 2017 (10.4 cases per 100,000 women). This pathology occurs most often in women 60-79 years old. 91% of the tumors were epithelial-stromal tumors, of which 75% were serous ovarian adenocarcinomas. Ovarian cancer in most cases was diagnosed at the third stage of the disease (47% of cases), which indicates a low level of early diagnosis of this tumor. Conclusion. In the Sumy region, a high incidence rate of ovarian cancer was revealed, which exceeds the national one and has a significant age dependence. Serous ovarian adenocarcinoma is the most common type of ovarian cancer. This pathology is diagnosed mainly at the 3rd stage.

Histology and Cell Biology: An Introduction to Pathology 5th Edition 2020

Linking basic science to clinical application throughout, Histology and Cell Biology: An Introduction to Pathology, 5th Edition, helps students build a stronger clinical knowledge base in the challenging area of pathologic abnormalities. This award-winning text presents key concepts in an understandable, easy-to-understand manner, with full-color illustrations, diagrams, photomicrographs, and pathology photos fully integrated on every page. Student-friendly features such as highlighted clinical terms, Clinical Conditions boxes, Essential Concepts boxes, concept mapping animations, and more help readers quickly grasp complex information. Features new content on cancer immunotherapy, satellite cells and muscle repair, vasculogenesis and angiogenesis in relation to cancer treatment, and mitochondria replacement therapies. Presents new material on ciliogenesis, microtubule assembly and disassembly, chromatin structure and condensation, and X chromosome inactivation, which directly impact therapy for ciliopathies, infertility, cancer, and Alzheimer’s disease. Provides thoroughly updated information on gestational trophoblastic diseases, molecular aspects of breast cancer, and basic immunology, including new illustrations on the structure of the T-cell receptor, CD4+ cells subtypes and functions, and the structure of the human spleen. Uses a new, light green background throughout the text to identify essential concepts of histology – a feature requested by both students and instructors to quickly locate which concepts are most important for beginning learners or when time is limited. These essential concepts are followed by more detailed information on cell biology and pathology. Contains new Primers in most chapters that provide a practical, self-contained integration of histology, cell biology, and pathology – perfect for clarifying the relationship between basic and clinical sciences. Identifies clinical terms throughout the text and lists all clinical boxes in the table of contents for quick reference. Helps students understand the links between chapter concepts with concept mapping animations on Student Consult™ – an outstanding supplement to in-class instruction. Student Consult™ eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, and references from the book on a variety of devices.

Myths and reality about the effects of glutamate. Compilation of scientific data of modern world literature

The aim of our scientific work was to study the existing experimental models of glutamate effects on the body and to understand the mechanisms of this effect and its possible consequences. To achieve this goal, we have studied different sources of scientific medical literature. Results. In a healthy body, glutamic acid is secreted by brain neurons in the required amount as a neurotransmitter and participates in the main information flows of human body. Sodium glutamate, which enters the body with food in large quantities, affects the body, causing general toxic effects and has a local effect on the stomach, intestines, salivary glands and pancreas and so on. Based on the scientific literature, experimental models that study the effects of glutamate are divided into two types: models in which glutamate enters the body orally and when glutamate is administered subcutaneously and intraperitoneally in the neonatal period of life. In the first route of administration, glutamate causes a toxic effect, which is manifested in increased catalytic activity in the blood serum of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltranspeptidase in 2.5; 1.6; and 1.5 times, respectively, while the activity of alkaline phosphatase remained at control levels, indicating a pronounced hepatotoxic effect of monosodium glutamate as a dietary supplement. It causes an increase in content of total and tyrosine-containing peptides in the blood serum, increase of substances of low and medium molecular weight, as well as an increase in the values of intoxication, which indirectly indicates a violation of the detoxification of endogenous metabolites in the liver of experimental animals. Ingestion of sodium glutamate within the recommended doses has not been shown to cause marked pathological changes in the mucous, muscular and serous membranes of the gastric wall, but there is a slight fullness of the vessels of the submucosal membrane. It has been found that in high doses, sodium glutamate has a local pathogenic effect on the tissues of the stomach, which consists in thinning all layers of its wall, desquamation of the mucous membrane and its disorganization by reducing the size of gastric glands, increasing the number of vessels and their fullness with blood. One of the mechanisms of pathogenic effect of sodium glutamate is the contact local and free radical oxidizing effect on gastric tissues. In the oral route of administration of glutamate there are no phenomena of fat growth (obesity) as epidermal, which is characteristic of the abdominal form of obesity, so and pararectal, parallelic, pararenal and retroperitoneal, which is characteristic for the visceral form of obesity. In the subcutaneous and intraperitoneal routes of administration of glutamate in the neonatal period of life in experimental animals, glutamate causes hypersecretion of hydrochloric acid, the development of lesions manifested by hemorrhage, erosions and ulcers in the gastric mucosa and obesity. Prolonged administration of monosodium glutamate significantly enhances the striking effects of stress on the gastric mucosa. Morphological studies of the submandibular salivary glands of rats on the background of glutamate-induced obesity confirm the development of pathological changes, as evidenced by the detected vacuolar dystrophy in the acinar region, perivascular and periductal edema. On the background of abdominal obesity, dystrophic processes were found in the acinuses and minor dystrophic changes in the intraparticle inserts. Conclusion. In the subcutaneous and intraperitoneal routes of administration of glutamate in the neonatal period of life in experimental animals, glutamate causes hypersecretion of hydrochloric acid, the development of lesions manifested by hemorrhage, erosions and ulcers in the gastric mucosa and obesity. Prolonged administration of monosodium glutamate significantly enhances the striking effects of stress on the gastric mucosa. Morphological studies of the submandibular salivary glands of rats on the background of glutamate-induced obesity confirm the development of pathological changes, as evidenced by the detected vacuolar dystrophy in the acinar region, perivascular and periductal edema. On the background of abdominal obesity, dystrophic processes were found in the acinuses and minor dystrophic changes in the intraparticle inserts. There is no doubt in the fact, which is based on the results of numerous experimental studies and covered in professional scientific litefrature, that the abdominal form of glutamate-induced obesity is possible only with subcutaneous and intraperitoneal routes of its administration in the neonatal period of life and while intraorall way of administration does not occur.

Dynamics of morphological manifestations of the experimental acute aspiration bronchopneumonia development.

Background. Currently, there is a need to create an experimental model for reproducing the main pathogenetic mechanisms of COVID-associated lungs damage. The first stage of such a model may be reproducing acute aspiration bronchopneumonia in rats. Objective. Examine the dynamics of morphological changes in the lungs in the development of experimental acute aspiration bronchopneumonia. Methods. The group of laboratory Wistar rats (n=25) in compliance with bioethical norms under typoental anesthesia was carried out operational intervention with the introduction of a sterile capron thread 2.5 cm long and a thickness of 0.2 mm to a depth of 2.5 cm. In the control group included 5 false-controlled animals. At 7, 14, 21, 28 and 56 days, the animals were derived from the experiment, morphological studies were carried out with the painting serial sections with hematoxylin-eosin. Results. On the 7 day, the morphological picture testified to the development of the acute stage of exudative inflammation with the full-blood of vessels, microtrombosis, dyslectasis, hyperplasia of alveolocytes II type. After 14 days, the proliferative stage was formed with alveolocytes hyperplasia, the epithelium of bronchi, as well as fibroblasts with the formation of sharp peribronchial and alveolar abscesses. After 21 days, the development of the lungs fibrosis with the organization of acute peribronchial and alveolar abscesses was noted, peribronchial and intraalveoli pronounced interstitial edema and the reactive hyperplasia of lymphoid follicles of a mixed nature. After 28 days, bronchopneumonia was organized in the form of fibrosis parenchyma, sections of chronic productive inflammation with the formation of resorbative granuloms; sections of the blood vessels hyalinose. For 56 days, these phenomena were progressed before the development of dense fibrosis (carnification) with sections of chronic abscesses with a formed by a connective tissue capsule, the development of vascular hyalinose. Conclusion. Thus, the model of acute aspiration bronchopneumonia reproduces the dynamics of morphological manifestations of acute lung damage, which is the basis for the development of pathogenetic therapy fields.

Age features of morphological changes of the hematotesticular barrier in experimental diabetes mellitus.

Background. Diabetes mellitus is an acute medical and social problem in all parts of the world due to the constant increase in the incidence of the disease, severe complications, disability and high mortality. Hyperglycemia leads to oxidative stress and increased processes of formation of active oxygen species, which in turn make a significant contribution to the development of male infertility. Objective. Therefore, the aim of our study was to establish morphological changes in the vessels of the hemomicrocirculatory flow and testicular sustentocytes of adult rats with experimental streptozotocin diabetes mellitus (SDM). Methods. The material for the study were the testicles of 20 sexually mature 6-month-old rats (weighing 150-180 g). SDM in animals of the experimental group was simulated by a single intraperitoneal injection of streptozotocin (dissolved in 0.1 M citrate buffer solution with a pH of 4.5) at a dose of 6 mg per 100 g of mass. An equivalent dose of 0.1 M citrate buffer was injected intraperitoneally to animals of the control group. Histological, electron microscopic, biochemical, morphometric and statistical research methods were used. Results. It was found that in the early stages of SDM (28th day) on the background of hyperglycemia in the hemomicrocirculatory flow of the testes there is a spasm of the vessels of the afferent link, which is confirmed by a decrease in the lumen of arterioles and an increase in their Wagenworth index. On the 70th day of SDM on the background of elevated levels of glucose and glycosylated hemoglobin in the links of the hemomicrocirculatory flow of the testis there are signs of diabetic microangiopathy, manifested by: hemorheological disorders in micro-hemo-vessels, (erythrocyte sludge, adhesion of erythrocytes and platelets, microclasmatosis), decrease in the capacity of arterioles and capillaries (increase in the Wagenworth index, respectively by 1.8 and 1.9 times), microclasmatosis, thickening and proliferation of the basement membrane of capillaries. Against the background of diabetic microangiopathy, there is a decrease in the number of sustentocytes by 0.01 mm2 of testicular parenchyma by 1.8 times, compared with control indicators, the area of their profile increases by 2.2 times (in all cases p<0.05). The nucleolar areas probably do not change, which leads to an increase in the nuclear-cytoplasmic ratio by 2.9 times (p<0.05). Such morphometric changes of sustentocytes are caused by development of vacuolar hydropic dystrophies in them, and an apoptosis that is confirmed by data of histo-ultrastructural studies. Changes in sustentocytes against the background of the development of diabetic microangiopathy lead to a violation of the hematotesticular barrier and to dystrophic changes in the spermatogenic epithelium of the testis. Conclusion. Thus, on the 70th day of SDM in the hemomicrocirculatory flow of the testis, the development of diabetic microangiopathy is observed, which leads to a violation of the hematotesticular barrier, and as a consequence, to a violation of spermatogenesis.

Assessment of bioscompatibility of isocyanurate-containing polyurethanes with ifosphamide by in vivo and in vitro methods.

Background. The creation of polymeric composite materials with pronounced biological activity, which are able to act as implants with local prolonged action of the immobilized substance can be widely used in medical practice. Objective. Study of cellular reactions of surrounding tissues of experimental animals to implantation of polymeric composite materials based on isocyanurate-containing polyurethanes with ifosfamide, study of histotoxicity of the obtained materials by tissue culture method. Methods. Polymeric composite materials based on isocyanate-containing polyurethanes without and with ifosfamide were implanted into the body of white laboratory Wistar rats. Cellular responses of the organism and possible changes in the structure of test specimens after implantation were studied by light microscopy by analysis of histological micropreparations. In order to study the peculiarities of the dynamics of growth and development of fibroblastic elements, the method of tissue culture was used. Results. Conducted biological studies by in vivo and in vitro methods allowed to evaluate the effect of immobilized ifosfamide in the structure of isocyanurate-containing polyurethanes on cellular reactions of surrounding tissues during implantation in experimental animals, as well as the effect of extracts from developed polymer samples on cultured cell growth. Conclusion. It was found that the implantation of isocyanurate-containing polyurethanes with ifosfamide led to the development of intense cellular reactions in the area of implant placement, primarily the reaction of round cell elements. The presence of ifosfamide in the structure of the polymeric implantation material probably affected the proliferation of cellular elements, inhibited regenerative processes in the early stages of the study and delayed the formation of a mature connective tissue capsule around the implanted samples. The tissue culture method showed that when making an extract of isocyanurate-containing polyurethanes with ifosfamide in the culture medium, there was a large variability of cell forms, which led to the appearance of macrophage-like elements.