Hyaluronic Acid as a LYVE-1 Receptor Ligand in the Lymphatic System of Healthy Human Skin.

Immunohistochemical detection of the LYVE-1 marker in healthy human full-thickness skin (the epidermis and the dermis) was carried out. LYVE-1 expression was found in the endothelium of lymphatic capillaries located in the papillary dermis, in the endothelium of larger lymphatic vessels of the reticular dermis, and in fibroblasts, which indicates their joint participation in hyaluronan metabolism. LYVE-1+ staining detected for the first time in cells of the stratum basale, the stratum spinosum, and the stratum granulosum of healthy human epidermis indicates their participation in hyaluronan metabolism and allows us to consider the spaces between epidermis cells as prelimphatics.

Polymorphism of Transforming Growth Factor TGFB and Its Receptors TGFBRI, TGFBRII, TGFBRIIII Genes in Western Siberia Patients with Open-Angle Glaucoma.

Polymorphism of genes of transforming growth factor TGFB and its receptors (TGFBRI, TGFBRII, and TGFBRIIII) in patients with primary open-angle glaucoma was analyzed. The frequency of the TGFBRII CC genotype in patients is increased relative to the control group (OR=6.10, p=0.0028). Heterozygosity in this polymorphic position is reduced (OR=0.18, p=0.0052). As the effects of TGF-ß is mediated through its receptors, we analyzed complex of polymorphic variants of the studied loci in the genome of patients. Two protective complexes consisting only of receptor genes were identified: TGFBRI TT:TGFBRII CG (OR=0.10, p=0.02) and TGFBRII CG:TGFBRIII CG (OR=0.09, p=0.01). The study showed an association of TGFBRII polymorphism with primary open-angle glaucoma and the need to study functionally related genes in the development of the disease, which should contribute to its early diagnosis and prevention.

Correlation of Cytokine Content in the Lymph with the Morphological Parameters of the Mesenteric Lymph Nodes in Adjuvant Therapy of Experimental Breast Cancer with the Use of Fragmented Human DNA.

We studied the relationship between the level of cytokines in the lymph of the thoracic duct and the morphometric parameters of the mesenteric lymph nodes after surgical treatment of breast cancer, chemotherapy, and administration of fragmented (double-stranded, dsDNA) human DNA. In comparison with surgical treatment and with chemotherapy alone, administration of a human dsDNA has a stimulating effect on the T-cell link of the immune response. In the paracortical zone, the relationship between the chemokine MCP-1 and increased content of small lymphocytes in this zone was revealed. Interrelations of IL-2 cytokines with small lymphocytes and of IL-4 with medium lymphocytes were revealed in germinal centers. We also observed interrelations of IL-7 with small lymphocytes and IL-4 with macrophages in the medullary cords, chemokine MIP-1α with immature and mature plasma cells (the number of these cells is reduced), and of MCP-1 with immunoblasts (the number of which is also reduced) in the medullary sinuses.

Effect of Photodynamic Therapy on the microRNA Level in Breast Cancer Tissues of Female Wistar Rats.

The expression of microRNA (miR-21, miR-221, miR-27a, and miR-429) was studied normal and tumor breast tissues of female Wistar rats before and after photodynamic therapy. In breast cancer, the levels of oncogenic microRNA (miR-21, miR-221, and miR-27a) were increased, while the level of tumor-suppressing miR-429 was reduced in comparison with the intact group. After photodynamic therapy, suppression of the expression levels of oncogenic microRNAs (miR-21, miR-221, and miR-27a) was noted. The level of tumor-suppressing miR-429 in breast tumor tissues remained reduced, as in the untreated breast cancer group.

Angioprotective and Follicle-Stimulating Effects of Administration of Bone Marrow Mesenchymal Stromal Cells in Chronic Inflammation of Internal Reproductive Organs.

Induced inflammation of reproductive organs in female Wistar rats was associated with an increase in the diameters of arteries and veins and number of blood vessels in the ovary medulla in combination with an increase in the number of lymphatic vessels; these changes were accompanied by reduction of the ovarian reserve and number of yellow bodies. Intravenous and submucosal injection of bone marrow multipotent mesenchymal stromal cells (BМ-ММSC) led to further increase in the diameters of arteries and veins and number of primordial and primary follicles. The injection of conditioned medium of BМ-ММSC cultures generally produced the same effects, which could demonstrate the secretory mechanisms of their influence on local angiogenesis and folliculogenesis.

Correlation between Structural Transformations in Mesenteric Lymph Nodes and the Levels MicroRNA during Polychemotherapy of Breast Cancer.

We studied interrelationships between the cytoarchitectonics of the mesenteric lymph node and the levels of microRNA-21, microRNA-221/222, and microRNA-429 in the lymph, blood serum, and breast tissues in female Wistar rats with chemically induced breast cancer. After polychemotherapy, significant correlations were found between miRNA-221 and the number of lymphoblasts in the germinal centers and between miRNA-222 and the number of lymphoblasts in the germinal centers and macrophages in the medullary cords of the mesenteric lymph nodes.

Influence of Surgical Treatment and Neoadjuvant Therapy of Chemically Induced Breast Cancer on Correlation of Cytokine Concentrations in the Lymph with Structural Transformations in the Mesenteric Lymph Nodes.

We performed a correlation analysis of the morphometry of mesenteric lymph nodes and cytokines of the thoracic duct lymph in chemically induced breast cancer (BC) and after surgical treatment of BC and neoadjuvant chemotherapy for BC according to the CMF scheme. After surgical treatment, correlations were found between the level of cytokines in the thoracic duct lymph and morphological changes in the mesenteric lymph nodes. The observed correlations can be a result of total resection of the tumor and increased immunomodulatory and antitumor action of cytokines. Comparison of the effect of chemotherapy and surgical treatment revealed correlations between cytokine concentrations in the lymph and structural changes in the lymph nodes, which can be related to weakening of local immunity and antitumor effect of cytokines.

Morphological Study of Mesenteric Lymph Nodes in Rats with Experimental Breast Cancer Treated with Fragmented Double-Stranded DNA.

We performed a morphometric analysis of mesenteric lymph nodes in rats with breast cancer induced by administration of N-methyl-N-nitrosourea. The volume of the paracortical zone and the number of mature plasma cells in the medullary sinuses were increased and the volume of lymphoid nodules with germinal centers and the number of macrophages were decreased in the group with tumor resection and chemotherapy in comparison with untreated rats with breast cancer. In rats receiving fragmented human double-stranded DNA in combination with adjuvant therapy, the volume of marginal and medullary sinuses and the number of small lymphocytes and macrophages in the paracortical zone increased in comparison with the group receiving chemotherapy without DNA preparation; the volume of lymphoid nodules with germinal centers returned to the level observed in the intact group; the volume of medullary substance and proliferative activity of cells in the germinal centers and medullary substance decreased, the number of mature plasma cells returned to normal in the medullary substance and decreased in the medullary sinuses.

Cytokines of the Lymph and Blood Serum as Markers of Oncogenesis and Efficiency of Therapy in Chemically Induced Breast Cancer in Wistar Rats.

We studied the levels of serum and lymph cytokines involved in the pathogenesis of BC. BC was induced by injection of N-methyl-N-nitrosourea to Wistar rats. The animals underwent surgery, or received polychemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil), or surgical treatment was combined with polychemotherapy; in a special group, Panagen (fragmented DNA) was added to polychemotherapy. Cytokine concentration in the lymph was measured using Bio-Plex Pro Rat Cytokoness 24-Plex Assay test system (Bio-Rad). In rats with BC, the content of most studied cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, MIP-1α, MIP-3α, RANTES, TNFα, and MCP-1) in the lymph and blood was significantly higher, while the content of IL-10 and GRO/KC was lower than in intact animals. Surgical resection of the tumor led to a significant decrease in the content of both pro- and anti-inflammatory cytokines in the lymph. Polychemotherapy led to a significant decrease in the content of IL-1ß, IL-4, IL-6, IL-7, MIP-1α, MIP-3α, and RANTES in the serum and lymph. Comparison of the cytokine content in the serum and lymph of operated animals after polychemotherapy with and without Panagen showed that the content of most cytokines (IL-5, IL-6, IL-7, IL-10, IL-13, IL-17A , IL-18, GRO/KC, IFNγ, and MIP-3α) was higher after Panagen administration.

Correlation Analysis of Morphological Changes of Structural and Functional Areas of Mesenteric Lymph Nodes with Cytokines of Lymph of Thoracic Lymphatic Duct in Experimental Breast Cancer.

We performed a correlation analysis of the morphometric parameters of mesenteric lymph nodes and cytokine content in the lymph of thoracic duct in rats with chemically induced breast cancer. The study showed that activity of the local immune response in the lymph nodes in breast cancer is aimed at antitumor protection. In breast cancer, the area of the paracortical zone remained at the level of the intact group, while the area of lymphoid nodules with germinative centers and the area of medullary substance increased; the number of macrophages in the thymus-dependent zone and zone responsible for humoral immunity also increased. The following positive correlations were revealed: in germinative centers and medullary substance, number of mitotic cells correlated with cytokine IL-5 content and the number of medium lymphocytes correlated with the content of chemokine MIP-1α; in the germinative centers, the number of immunoblasts correlated with the level of cytokine GRO/KC, in the paracortical zone, the number of macrophages correlated with the level of chemokine MCP-1, the number of reticular cells correlated with IL-6 and M-CSF content; in medullary substance, the number of small lymphocytes and mature cells plasma cells (their content was reduced) correlated with the level of chemokine GRO/KC, which can be caused by their migration from the lymph node.

Treatment of Intervertebral Disc Degeneration in Wistar Rats with Mesenchymal Stem Cells.

We studied the effect of erythropoietin on functional properties of mesenchymal stem cells under conditions of oxidative stress and their therapeutic potential in the treatment of intervertebral disc degeneration in Wistar rats. It was shown that erythropoietin stimulates proliferation under conditions of oxidative stress. Injection of bone marrow mesenchymal stem cells into the damaged intervertebral disc was followed by an increase in the height of the intervertebral disc and activation of repair processes in the nucleus pulposus. The combination of mesenchymal stem cells with erythropoietin provides the best effect of cell therapy in case of intervertebral disc damage.

Correlation of the Levels of microRNA with Cell Composition of Axillary Lymph Node in Wistar Rats with Breast Cancer.

We studied the levels microRNA (miR-21, miR-221, miR-222, and miR-429) in blood serum, thoracic duct lymph, and breast cancer tissue, as well as the cell composition of the axillary lymph node in Wistar female rats with chemically induced breast cancer. The levels of miR-221 and miR-429 in the tumor tissue and in the lymph correlated with the decrease in lymphocyte number in the medullary cords of the axillary lymph nodes.

Changes in the Circulatory and Lymphatic Systems of Internal Genitals in Female Rats after Intravenous and Lymphotropic Administration of Multipotent Mesenchymal Stem Cells and Products Secreted by These Cells.

We studied the effects of intravenous and lymphotropic administration of bone marrow multipotent mesenchymal stromal cells and products secreted by these cells into conditioned medium on the blood and lymph circulation in the uterus and ovaries, as well as on folliculogenesis in female Wistar rats. It was shown that stromal cells and conditioned media of these cells administered via both routes lead to an increase in the number and diameter of blood vessels in the uterine wall and in the cortical layer of the ovaries. Neither mesenchymal stromal cells, not conditioned media affected the ovarian follicular apparatus.

[Ghrelin deficiency in patients with type 2 diabetes: the relationships with obesity, adipose tissue dysfunction and glucose variability].

AIM: Ghrelin, a peptide hormone mostly produced by stomach, plays an important role in regulation of feeding behavior, energy balance and glucose homeostasis. THE AIM: to determine the relationships between fasting serum levels of ghrelin, body composition, adipose tissue endocrine function and glucose variability (GV) in type 2 diabetic subjects with and without obesity. MATERIALS AND METHODS: We observed 124 individuals with type 2 diabetes, including 42 non - obese subjects and 82 patients with obesity. Thirty non - obese healthy subjects were acted as control. The concentrations of ghrelin, leptin, resistin, and visfatin in the fasting serum were determined by Multiplex analysis. Body composition was assessed with DEXA. The 24-hour and nocturnal GV parameters were derived from continuous glucose monitoring. RESULTS AND DISCUSSION: Ghrelin levels in patients with diabetes were decreased significantly as compared to control (p.

Effect of Neoadjuvant and Adjuvant Therapy of Experimental Breast Cancer on the Structure of Mesenteric Lymph Nodes.

The morphometric analysis of mesenteric lymph nodes was carried out in female Wistar rats with chemically induced breast cancer. In control rats with untreated breast cancer, the volume of the system of sinuses increased in parallel with the appearance of morphological signs of suppression of cell-mediated immunity, inhibition of humoral immunity, and macrophage reaction. Against the background of chemotherapy, we observed a decrease in the volume of paracortex and lymphoid nodules, suppression of proliferative activity of lymphoid cells in paracortical and B-cell zone, and a decrease in macrophage content. After resection of breast cancer followed by chemotherapy course, lymph transport activation, widening of the paracortex, enhanced proliferative activity of cells in the paracortex and B-cell zone, and reduced volumes of lymphoid nodules with and without germinal centers and medullary substance were revealed in comparison with rats subjected neoadjuvant chemotherapy.

Blood Serum Levels of Proinflammatory Cytokines (IL-1ß, IL-6, TNFα, IL-8, IL-12p70, and IFNγ) in Patients with Uterine Myoma.

We analyzed cytokine profile in blood serum of patients with uterine myoma and revealed significantly reduced level of IFNγ and a tendency towards a decrease in the levels of IL-1ß and TNFα; the levels of IL-6, IL-8, and IL-12p70 did not differ from those in healthy women. The drop in the concentrations of factors responsible for inflammation and angiogenesis in tissues are unfavorable for proliferation and differentiation of the uterine tissues.

Effect of Lithium Preparations on Cerebral Electrophysiological Activity in Rats.

The study examined the effects of a novel neurotropic medication based on a lithium complex composed of lithium citrate, polymethylsiloxane, and aluminum oxide on electrophysiological parameters of the rat brain. In contrast to lithium carbonate (the reference drug), the novel preparation resulted in a wave-like dynamics of electrical activity in the visual cortex. Rhythmic photic stimulation of the rats treated with lithium carbonate resulted in appearance of the signs attesting to up-regulation of excitability of cerebral cortex in all examined ranges. In contrast, the complex lithium preparation diminished the delta power spectrum, which was the only affected frequency band. It is hypothesized that the complex lithium medication induces milder activation of the cerebral cortex in comparison with lithium carbonate. The novel medication composed of lithium citrate, aluminum oxide, and polymethylsiloxane, is characterized by greater efficacy and safety than the preparation based on inorganic lithium salt (lithium carbonate).

Effect of Bone Marrow Multipotent Mesenchymal Stromal Cells on Blood and Lymphatic Vasculature in Uterine Wall of Wistar Rats during Experimental Chronic Metroendometritis.

The study examined the effect of bone marrow multipotent mesenchymal stromal cells and their products secreted into the conditioned medium on uterine microcirculatory bed in Wistar rats during chronic inflammation. The parameters of blood and lymphatic microcirculation in the uterus changed in various directions in relation to the administration routes of biomedical cell product, which is important when the cell therapy is employed in the treatment of inflammatory-degenerative alterations in the lesser pelvis organs.

[Lymphatic system of the eye]. / Limfaticheskaia sistema glaza.

Existence of lymphatic outflow of intraocular fluid is still an open question. Identification of the lymphatic capillaries and vessels in various human organs in normal and pathological conditions became possible with discovery of endotheliocyte markers for lymphatic vessels. However, the available information on the presence of lymphatic structures in the human eye is inconsistent and uncertain. The data on lymphatic drainage of the eye is of interest, particularly because it may help understand glaucoma pathogenesis, mechanisms of development of eye inflammatory diseases, and develop pathogenetic therapies. The article reviews literature and presents the authors' own views on lymphatic drainage of the human eye.

Effect of Various Treatment Modes of Experimental Mammary Gland Tumor on Structure of Anterior Mediastinal Lymph Nodes.

The effects of various treatment modes on the morphology of anterior mediastinal lymph nodes were examined in female Wistar rats with chemically provoked breast cancer. Adjuvant chemotherapy impaired filtration barrier potential of the anterior mediastinal lymph nodes, which manifested in increased volume of sinuses, reduced volumes of lymphoid nodules with germinal centers and thymus-dependent regions, down-regulated proliferative activity of lymphoid cells in B-cell zone and paracortex, and diminished macrophage score in all zones. Intraperitoneal injection of double-stranded DNA preparation (5 mg/kg) activated the humoral and cellular immune responses manifested by morphological alterations in anterior mediastinal lymph nodes observed in parallel with a decrease of medullary sinuses volume: enhancement of lymphocyte volume and lymphocyte score in paracortex, mantle zone expansion, and an increase of volume of the light centers in lymphoid nodules paralleled with diminished proliferative activity in them.