It is a common fact, that the content of sex hormones in humans and animals varies in different age periods. The functional state of the immune system also changes with age. However, sex differences ...studies of inflammatory and immune responses during puberty prevail in literature. Investigation of immune responses to LPS peculiarities in prepubertal females and males may contribute to the development of more effective immunotherapy and minimize side effects of children vaccination. Therefore, the aim of this work was to investigate the LPS-induced SIRS sex differences in prepubertal Wistar rats. Despite the absence of sex differences in estradiol and testosterone levels, LPS-induced inflammatory changes in liver and lungs are more pronounced among males. Males demonstrate the increasing neopterin, corticosterone levels and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Not less important is that in females, demonstrating less morphological changes in liver and lungs, endotoxin level is tenfold higher, and corticosterone level decreases. Thus, endotoxin cannot be used as a marker of the severity of multiple organ failure in prepubertal period. The LPS-induced immune reactions in females and males are similar and are characterized by immunosuppression. Both females and males have decreased production of cytokines (IL-2, IL-4, TNF-α, TGF-β) and the absolute number of CD3 + and CD3 + CD8 + lymphocytes in blood. The acute atrophy of thymus and apoptosis of thymic cells are revealed in animals of both sexes. However, the number of CD3 + CD4 + T-helpers and CD4 + CD25 + Foxp3 + T-cells decreases only in females with SIRS, and in males there was a decrease of CD45R + B-cells. The least expressed sex differences in immune responses in the prepubertal period can be determined by the low levels of sex steroids and the absence of their immunomodulatory effect. Further studies require the identification of mechanisms, determining the sex differences in the inflammatory and immune responses in prepubertal animals.
The aim of the study was to characterize the severity of the systemic inflammatory response induced by lipopolysaccharide (LPS) in animals with different resistance levels to hypoxia.
Two to three ...months old male Wistar rats (220-240 g) were divided according to hypoxia tolerance in a hypobaric chamber. After a month, they were injected intraperitoneally with
LPS at a dose of 1.5 mg/kg. After 3, 6 and 24 hours of LPS injection, we studied the levels of IL-1β, C-reactive protein (CRP) and TGF-β in the serum, the expression of
α and
in the liver, morphological disorders in the lung and ex vivo production of IL-10 by splenic cells activated by ConA.
In the early periods after the injection of LPS, increase in
expression in the liver was observed only in the rats susceptible to hypoxia. After 6 hours of LPS injection, the number of neutrophils in the interalveolar septa of the lungs of rats susceptible to hypoxia was higher than in tolerant rats. This points to the development of more pronounced LPS-induced inflammation in the rats susceptible to hypoxia and is accompanied by increased expression of
α in the liver after 6 hours of LPS administration, serum IL-1β level after 3 hours and CRP level after 24 hours. The production of the anti-inflammatory cytokine IL-10 by the spleen was significantly decreased after 6 hours of LPS injection only in the animals tolerant to hypoxia. After 24 hours of LPS injection, a significant decrease in serum TGF-β level occurred in the rats tolerant to hypoxia in comparison with the control group, which improved the survival rates of the animals.
We have demonstrated the differences in the severity of the LPS-induced inflammatory response in male Wistar rats with different resistance levels to hypoxia. Rats susceptible to hypoxia are characterized by a more pronounced inflammatory response induced by LPS.
On the model of the systemic inflammatory response (SIRS), induced by lipopolysaccharide (LPS), the morphological and functional changes in the thymus and spleen and the subpopulation composition of ...peripheral blood lymphocytes of rats differing in resistance to hypoxia were studied. It was demonstrated that the level of endotoxin in blood serum after 3 hours of LPS administration in susceptible-to-hypoxia rats was 64 times higher than in the control group, while in tolerant-to-hypoxia animals it was only 8 times higher in 6 hours. After 24 hours of LPS injection, only in susceptible-to-hypoxia rats did the level of C-reactive protein in blood serum increase. There is a difference in the dynamics of morphological changes of lymphoid organs after LPS injection in tolerant- and susceptible-to-hypoxia animals. After 3 hours of LPS administration, the tolerant-to-hypoxia rats showed no changes in the thymus, spleen, and subpopulation composition of lymphocytes in peripheral blood. After 6 hours there was only a decrease in B-lymphocytes and increase in cytotoxic T-lymphocytes and NK cells. After 1 day of LPS injection, the tolerant-to-hypoxia rats had devastation in PALS of the spleen. After 3 hours of LPS injection the susceptible-to-hypoxia animals had reactive changes in the lymphoid organs: decrease of the thymus cortex, narrowing of the marginal zones of spleen lymphoid follicles, widening of their germinal centers, and a decrease in the absolute number of cytotoxic T-lymphocytes, NK cells, and B-lymphocytes. After 24 hours of LPS injection the tolerant-to-hypoxia animals had a greater absolute number of T-lymphocytes and NK cells in comparison with the susceptible rats. Thus, in animals with different resistance to hypoxia the LPS-induced SIRS is characterized by different dynamics of morphological and functional changes of the thymus and spleen. The obtained data will serve as a basis for the development of new individual approaches to the prevention and treatment of infectious and inflammatory diseases.
It was found that the mutations in the SDHD gene, encoding one of subunits of the succinate dehydrogenase complex, lead to the development of head and neck paraganglioma (HNPGL). We analyzed this ...gene in 91 patients with HNPGL from Russia.
DNA was isolated from the whole blood. A screening for mutations was performed by Sanger sequencing.
We revealed three missense mutations that have been described previously: p.Pro81Leu, p.His102Arg, p.Tyr114Cys. Moreover, we identified a novel potentially pathogenic variant (p.Trp105*).
We found that mutations in the SDHD gene were less common in Russian patients compared with the majority of European populations. It was shown that the p.His102Arg mutation is a major mutation in Russia. We confirmed the previous suggestion that a bilateral localization of the tumor and the carotid type represent a marker of the genetically determined form of HNPGL.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The environmental pollution by microplastics is a global problem arising from the extensive production and use of plastics. Small particles of different plastics, measured less than 5 mm in diameter, ...are found in water, air, soil, and various living organisms around the globe. Humans constantly inhale and ingest these particles. The associated health risks raise major concerns and require dedicated evaluation.
In this review we systematize and summarize the effects of microplastics on the health of different animals. The article would be of interest to ecologists, experimental biologists, environmental physicians, and all those concerned with anthropogenic environmental changes.
We searched PubMed and Scopus from the period of 01/2010 to 09/2021 for peer-reviewed scientific publications focused on (1) environmental pollution with microplastics; (2) uptake of microplastics by humans; and (3) the impact of microplastics on animal health.
The number of published studies considering the effects of microplastic particles on aquatic organisms is considerable. In aquatic invertebrates, microplastics cause a decline in feeding behavior and fertility, slow down larval growth and development, increase oxygen consumption, and stimulate the production of reactive oxygen species. In fish, the microplastics may cause structural damage to the intestine, liver, gills, and brain, while affecting metabolic balance, behavior, and fertility; the degree of these harmful effects depends on the particle sizes and doses, as well as the exposure parameters. The corresponding data for terrestrial mammals are less abundant: only 30 papers found in PubMed and Scopus deal with the effects of microplastics in laboratory mice and rats; remarkably, about half of these papers were published in 2021, indicating the growing interest of the scientific community in this issue. The studies demonstrate that in mice and rats microplastics may also cause biochemical and structural damage with noticeable dysfunctions of the intestine, liver, and excretory and reproductive systems.
Microplastics pollute the seas and negatively affect the health of aquatic organisms. The data obtained in laboratory mice and rats suggest a profound negative influence of microplastics on human health. However, given significant variation in plastic types, particle sizes, doses, models, and modes of administration, the available experimental data are still fragmentary and controversial.
Background
Colorectal cancer (CRC) is the third most common cancer. It is a heterogeneous disease, including both hereditary and sporadic types of tumors. CRC results from complex interactions ...between various genetic and environmental factors. Inflammatory bowel disease is an important risk factor for developing CRC. Despite growing understanding of the CRC biology, preclinical models are still needed to investigate the etiology and pathogenesis of the disease, as well as to find new methods of treatment and prevention.
Objectives
The purpose of this review is to describe existing murine models of CRC with a focus on the models of colitis-associated CRC. This manuscript could be relevant for experimental biologists and oncologists.
Methodology
We checked PubMed and Google from 01/2018 to 05/2023 for reviews of CRC models. In addition, we searched PubMed from 01/2022 to 01/2023 for articles using the azoxymethane (AOM)/dextran sulfate sodium (DSS) CRC model.
Results
Existing murine models of CRC include spontaneous, genetically engineered, transplantation, and chemically induced models. For the study of colitis-associated cancer (CAC), the AOM/DSS model is predominantly used. This model is very similar in histological and molecular characteristics to the human CAC, and is highly reproducible, inexpensive, and easy to use. Despite its popularity, the AOM/DSS model is not standardized, which makes it difficult to analyze and compare data from different studies.
Conclusions
Each model demonstrates particular advantages and disadvantages, and allows to reproduce different subtypes or aspects of the pathogenesis of CRC.
The aim of this work was to compare mesoporous carriers based on silica and magnesium aluminosilicate in the amorphous solid dispersion production. Darunavir has been selected as an active ...pharmaceutical ingredient that is classified as a Class 2 BCS substance and exists in two commercially available forms: crystalline ethanolate and amorphous. In the course of the study, the conditions for the preparation of amorphous samples with the selected carriers were evaluated within the framework of the most common methods for obtaining solid dispersions - hot-melt extrusion, solvent wetting, and spray drying. It was determined that the obtained dispersion properties almost completely repeat the properties of the corresponding carriers. The resulting dispersions were examined in a dissolution test and the best ones was used to formulate tablets, which were studied in an in vitro dissolution test with the original Prezista. The proposed tablet formulation showed improved dissolution compared to the original one. It was also found that silica supports have a greater positive contribution to darunavir dissolution - both ethanolate or amorphous forms.
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The aim of the work is to study the differences in the severity of negative experiences associated with certain aspects of the internal picture of the disease in children undergoing inpatient ...treatment for respiratory tuberculosis (RT) and children with leukemia, as well as in different age groups of children with RT. Sampling and methods. The study data are presented on a sample of patients aged 5 to 13 years (N= 42, 9 boys, 33 girls), divided into subgroups of 5—7 years, 8—11 years and 12—13 years. The technique of “Unfinished Sentences” by V.E. Kagan and I.K. Shatts was used. At the first stage, the level of negative experiences was compared between groups of children with RT, with leukemia and healthy children (using data from the I.K. Schatz study), at the second stage — in different age groups of children with RT. Conclusions. The results showed a higher level of negative experiences in the group of children with RT due to the absence of severe symptoms and, as a result, difficulties in understanding the need to stay in the hospital. The factors of negative experience in children of different age groups were revealed. Conclusions are formulated about the need to take into account age-related features and the specifics of the disease when developing psychological support programs.
Целью работы является изучение различий в выраженности негативных переживаний, связанных с отдельными аспектами внутренней картины болезни (ВКБ) у детей, находящихся на стационарном лечении туберкулеза органов дыхания (ТОД) и детей с лейкозом, а также в разных возрастных группах детей с ТОД. Выборка и методы. Представлены данные исследования на выборке пациентов от 5 до 13 лет (N = 42, 9 мальчиков, 33 девочки), разделенной на подгруппы 5—7 лет, 8—11 лет и 12—13 лет. Использовалась методика «Незаконченные предложения» В.Е. Кагана и И.К. Шаца. На первом этапе проведено сравнение уровня негативных переживаний между группами детей с ТОД, с лейкозом и здоровых детей (с использованием данных исследования И.К. Шаца), на втором этапе — в разных возрастных группах детей с ТОД. Выводы. Результаты показали более высокий уровень негативных переживаний в группе детей с ТОД, что обусловлено отсутствием у них тяжелых симптомов и, как следствие, трудностями в понимании необходимости нахождения в стационаре. Выявлены факторы негативных переживаний у детей разных возрастных групп. Сформулированы выводы о необходимости учета возрастных особенностей и специфики заболевания в разработке программ психологического сопровождения.
Microplastic pollution poses a threat to human health. It is possible that the increase in the incidence of inflammatory bowel disease is associated with exposure to microplastics. We investigated ...the effect of the consumption of polystyrene microparticles with a diameter of 5 μm at a dose of 2.3 mg/kg/day for 6 weeks on morphological changes in the colons of healthy male C57BL/6 mice and of mice with acute colitis induced by a 1% dextran sulfate sodium solution (DSS). In healthy mice, microplastics caused an increase in the number of endocrine cells, an increase in the content of highly sulfated mucins in goblet cells, an increase in the number of cells in the lamina propria, and a decrease in the volume fraction of macrophages. Microplastic consumption caused more severe acute colitis, which is characterized by a greater prevalence of ulcers and inflammation and a decrease in the content of neutral mucins in goblet cells.
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