2,252 research outputs found
Клетки иммунной системы и регуляция регенерации
This study proposes a theory of immune regulation of regeneration of damaged tissues. An assessment of the role of macrophages, lymphocytes, mast cells, platelets, and endothelial cells in the reconstruction of the structure of the functional element of the defective organ. Discusses the mechanisms of interaction of immune cells during regeneration. Presents the main factors determining the differentiation of stem cells. Apoptosis is considered as one of the components of the recovery process. Предложена теория иммунологической регуляции регенерации тканей. Дана оценка роли макрофагов, лимфоцитов, тучных клеток, тромбоцитов, эндотелиоцитов в восстановлении структуры функционального элемента поврежденного органа. Обсуждаются механизмы взаимодействия клеток иммунной системы в процессе регенерации. Представлены основные факторы, определяющие дифференцировку стволовых клеток. В качестве одного из компонентов восстановительного процесса рассматривается апоптоз.
Precursors, pathways of carcinogenesis and molecular markers of vulvar squamous cell carcinoma. Literature review
The review analyzes and summarizes the results of the studies on the pathogenesis of vulvar squamous cell carcinoma and its diagnostic features, reviews precursors and molecular subtypes of carcinomas. Despite the relatively low incidence of this tumor, over the past few decades, there has been an upward trend in its incidence, including the incidence among young women. According to the latest World Health Organization classification of lower genital tumors from 2020, vulvar squamous cell carcinoma is divided into human papillomavirus (HPV) associated and HPV-independent. While these carcinomas are often morphologically similar, their mechanisms of carcinogenesis, precursors, and clinical outcomes are different. Just the detection of virus DNA in a tumor is not enough to establish HPV status. Meanwhile immunohistochemical detection of the expression of p16 and p53 proteins allows not only to separate two pathogenetic pathways of carcinogenesis, but also to identify its molecular subtypes. The data on the possible use of p16 and p53 expression as the disease prognosis molecular markers have been obtained. Currently, the tactics of treatment and monitoring patients does not depend on the HPV status of carcinoma; however, the results of recent studies suggest that women with HPV positive vulvar cancer have significantly higher survival rates and a lower risk of recurrence. Understanding the mechanisms of carcinogenesis and improving its diagnosis will advance the assessment of the individual risk of the progression of precancerous lesions, as well as the outcome and the occurrence of tumor recurrence
MAST CELLS AS BIOMARKERS OF INFLAMM-AGEING
Most mechanisms of ageing are believed to be more or less associated with inflammation. With age, a unique form of chronic inflammation develops which is termed as “inflamm-ageing”. The mechanisms of this process are still not fully clear due to the lack of reliable assessment criteria. Immune system is among those involved in accelerating age-related changes in the body. It also directly participates in the process of inflammation. In its pathogenesis, the reaction of mast cells may be of great importance. The role of mast cells in tissue remodeling deserves special attention, since the latter event is among the main features associated with ageing. Hence, the “inflamm-ageing” is considered a sufficient indicator of ageing, and the mast cells could provide biomarkers of this process. In order to test the proposed hypothesis, the present study was conducted to determine age-related morpho-functional changes in mast cell populations in various organs in rats. Some morpho-functional parameters of mast cells (number, synthetic and functional activity, degree of maturation) in different animal organs were evaluated in male Wistar rats of different ages (4 months and 2 years). We have found the age-dependent changes upon examination of thymus, adrenal glands, and skin, i.e., a decrease in the number of mast cells and their synthetic capacity, along with significantly increased functional activity. In the stomach, small and large intestines, at the constant number of mast cells, we revealed a decrease in their synthetic ability, and increased functional activity. These changes were accompanied by enlargement of blood vessels in the studied organs. Liver is the only organ which did not exhibit any changes in mast cell populations with age. The detected changes in mast cell populations may play an important role in formation of “inflamm-ageing” events, which accompany the ageing processes, because these cells are an integral component of inflammatory response. The progression of “inflamm-ageing” leads to accumulation of cytokines and pro-inflammatory mediators in tissues, which, in turn, activate the mast cells. At the same time, increased degranulation of mastocytes may promote the process of “inflamm-ageing”. The oberved mutual influence of mast cells and “inflamm-ageing” makes it possible to consider mastocytes as potential candidates for searching the biomarkers in “inflamm-ageing”. © 2022, RSI
Influence of macrophages on the insulin-synthesizing system under normal conditions and in alloxan diabetes
Insulin-synthesizing cells (ISCs) of pancreatic gland are localized both in its islets, and in exocrine portion, as single cells or cellular agglomerates. ISCs differ in their morphological and functional characteristics, depending on characteristics of the microenvironment. Resident macrophages are also involved into formation of their microenvironment. Our purpose was to assess the effect of functional macrophages upon the insulinsynthesizing system (pancreatic islets, cell agglomerates, and separately lying insulin-synthesizing cells) under normal conditions and in alloxan diabetes.Alloxan diabetes was induced in mature male Wistar rats by intraperitoneal injection of alloxan (30 mg/100 g). Functional activity of macrophages was modeled with anti-inflammatory drug aminophthalhydrazide (AMP). Contents of insulin, glucose, and glycosylated hemoglobin were measured in blood of experimental animals. The levels of IL-1α, TNFα and IFNγ were determined in pancreatic homogenate. The number of macrophages was counted in histological preparations from the insular and exocrine parts of the organ, as well as the number of pancreatic islets, agglomerates, and single ISCs. The amounts of proliferating cells (insulin+Ki-67+), apoptotic forms (TUNEL+insulin+), and insulin content of ISCs at different sites (according to their fluorescence intensity) were determined. All pancreatic islets were divided into 3 types, according to intensity of insulin fluorescence, i.e., islets with high, median and low levels of fluorescence.In healthy rats, immunomodulation reduced total level of IL-1α in pancreatic parenchyma, without changing the overall parameters of carbohydrate metabolism. In the exocrine part of pancreas, the content of single ISCs in ductal epithelium was increased. Likewise, proliferation of the ISC agglomerates became higher. The intensity of β-cell apoptosis increased in pancreatic islets. The proportion of islets with high-level insulin fluorescence was decreased, along with lower density of macrophages and proliferation rates of β-cells, and higher apoptosis rates, than in intact animals. We have also revealed there an increased ratio of cells with average insulin levels. In the islets with low insulin content, immunomodulation did not cause morphological changes. Administration of AMP in alloxan diabetes contributes to a significantly decreased concentration of IFNγ in pancreatic tissues, stabilizes IL-1α content, along with reduced apoptosis of ISCs and macrophage infiltration in all parts of the gland. In the ductal epithelium, a large number of single ISCs with high synthetic activity was observed, with retained number of agglomerates and their increased cellularity. The number of dividing β-cells is increased in pancreatic islets.Modulation of the functional activity of pancreatic macrophages under physiological conditions provides a multidirectional effect on the insulin-synthesizing cells, depending on their localization. In exocrine part of the organ, where M2 macrophages are located, we have observed activated differentiation and proliferation of ISC precursors. Meanwhile, in the islets where M1 macrophages are present, apoptosis of β-cells was enhanced. In alloxan diabetes, immunomodulation was associated with reduced destruction of insulinocytes, along with high intensity of their proliferation. Heterogenous response of ISCs to the changes in the microenvironment depends on their synthetic activity. In healthy rats, the islets with high level of insulin fluorescence, the level of apoptosis is increased, and β-cell proliferation is reduced, while the morphological and functional characteristics of islets with low-level insulin fluorescence did not change. In alloxan diabetes, apoptosis prevailed in islets with high fluorescence values, whereas β-cell proliferation predominated in the islets with low insulin contents
TOXIC LIVER DAMAGE IN ACUTE PHASE OF ETHANOL INTOXICATION AND ITS EXPERIMENTAL CORRECTION WITH CHELATE ZINC COMPOUND
It was established, that ethanol in the dose of 12 g/kg in experimental animals (white non-inbred male rats) had. expressed damaging effect on the liver, that is shown in statistically significant increase of activity of hepatic enzymes (alanine aminotransferase, alkaline phosphatase), hypoglycemia, development of albuminous and. hydropic degeneration. It is proved, that application of new chelate zinc (2,8,9-trigidrotsinkatrane) in experimental correction of acute ethanol poisoning promotes reduction of metabolic and morphological derangements
OXIDATIVE STRESS AS A PATHOGENETIC LINK OF ACUTE ETHANOL POISONING AND ITS CORRECTION WITH CHELATE ZINC COMPOUNDS
The data on the expressed toxic effect of ethanol in dose DL50 (12 g/kg) on experimental rats were received. The toxic effect was expressed in significant stimulation of processes of lipid peroxidation against the background of antioxidant system suppression. While evaluating the results of statistic analysis it was proved, that new chelate zinc (2,8,9-trihydrozincatrane) in the protective dose of 4 mg/kg under conditions of the acute ethanol poisoning reduces the severity of oxidative stress and normalizes indicators of antioxidant system
Половые отличия пула свободных аминокислот-нейромедиаторов у крыс Крушинского-Молодкиной
The study of the role of neurotransmitter systems in the pathogenesis of epilepsy is one of the priorities of epileptology. New data on the functions of free neurotransmitter-like amino acid in the central nervous system are of the greatest importance and determine the prospects for the development of novel effective anticonvulsants. It is widely believed in clinical medicine that epilepsy has distinct gender characteristics. The aim of this study was to investigate the gender peculiarities in the content of neurotransmitter amino acids in the brain of Krushinsky-Molodkina (KM) rats, which were used as model organisms for the study of genetically induced audiogenic epilepsy. The content of Asp, Glu, GABA, Gly, and Tau of the medulla oblongata, hippocampus and cerebral cortex were determined using high-performance liquid chromatography (HPLC) in intact KM rats, KM rats exposed to a series of epileptiform seizures, and Wistar rats (control group). Both the Wistar and KM rats had gender distinctions in the distribution of free amino acids among the investigated brain parts. The audiogenic epilepsy was characterized by smoothing gender differences as well as differences between the concentrations of free amino acids in the cortex and medulla oblongata, specific for Wistar rats. The changes observed in male rats after the set of seizures included the increase in GABA concentration and a decrease in the Gly level in all investigated brain parts, as well as the decrease of the Tau content in the cortex and hippocampus. At the same time, the Glu content in cortex increased, while the Asp level decreased. After 6 days of audiogenic stimulations the female KM rats demonstrated the increase in the Glu level in all investigated brain parts, the increase in Gly and Asp levels in hippocampus, and no changes in the GABA content. Thus, after the set of epileptiform seizures the KM rats achieved a new steady state of the studied amino acids pool, which differed in males and females. In this case, gender differences significantly changed after the seizures. © 2020 Russian Academy of Medical Sciences. All rights reserved.The work was performed within the framework of the state task of the IIF UB RAS (Registration number AAAA-A18-118020590108-7)
Ultrathin Tropical Tropopause Clouds (UTTCs) : I. Cloud morphology and occurrence
Subvisible cirrus clouds (SVCs) may contribute to dehydration close to the tropical tropopause. The higher and colder SVCs and the larger their ice crystals, the more likely they represent the last efficient point of contact of the gas phase with the ice phase and, hence, the last dehydrating step, before the air enters the stratosphere. The first simultaneous in situ and remote sensing measurements of SVCs were taken during the APE-THESEO campaign in the western Indian ocean in February/March 1999. The observed clouds, termed Ultrathin Tropical Tropopause Clouds (UTTCs), belong to the geometrically and optically thinnest large-scale clouds in the Earth´s atmosphere. Individual UTTCs may exist for many hours as an only 200--300 m thick cloud layer just a few hundred meters below the tropical cold point tropopause, covering up to 105 km2. With temperatures as low as 181 K these clouds are prime representatives for defining the water mixing ratio of air entering the lower stratosphere
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