V. I. Konenkov

Effects of Melatonin, Aluminum Oxide, and Polymethylsiloxane Complex on the Expression of LYVE-1 in the Liver of Mice with Obesity and Type 2 Diabetes Mellitus

The effects of melatonin, aluminum oxide, and polymethylsiloxane complex on the expression of LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) in the liver were studied in db/db mice with experimental obesity and type 2 diabetes mellitus. The complex or placebo was administered daily by gavage from week 8 to week 16 of life. The animals receiving the complex exhibited enhanced, in comparison with the placebo group, immunohistochemical LYVE-1+ staining of endothelial cells in sinusoids. Enhanced expression of LYVE-1 was associated with less pronounced dilatation of interlobular arteries, veins, and lymphatic vessels. Thee findings suggest a protective effect of the complex towards structural changes in the liver of mice with obesity and type 2 diabetes.

Changes in the Structure of the Thymus under Conditions of Various Treatments for Experimental Mammary Tumor

Morphological changes in the thymus of female Wistar rats with experimental mammary gland carcinomas were studied. After adjuvant therapy, the area of the cortical matter and density of parenchymal cells in the thymus decreased, while areas of the medulla, connective tissue, and content of immunoblasts and macrophages increased. In the thymuses of rats receiving exogenous DNA, morphological signs of activation of the lymphoid and epithelial components were found: areas of the cortex and medulla, glandular and connective tissue corresponded to the values in intact animals, the counts of lymphocytes in the central part of the cortical matter and of macrophages in all zones of the thymus increased, and lymphocyte migration from the thymus increased (in comparison with the chemotherapy group).

The Thymus in Experimental Mammary Carcinogenesis and Polychemotherapy

Histological study of structural transformations in the thymus of Wistar females in induced carcinogenesis (N-methyl-N-nitrosourea injection in the right 2-nd mamma) and polychemotherapy (6 months after tumor growth initiation; cyclophosphamide, methotrexate, and 5-fluorouracyl) was carried out. The area of the cortical matter in the thymus decreased 6 months after carcinogenesis induction, the percentage of connective tissue elements and glandular tissue and the counts of immunoblasts and cells with pyknotic nuclei increased, this indicating the development of accidental involution of the thymus. Animals of the experimental tumor+chemotherapy group exhibited morphological signs of lymphocyte migration from the thymus and suppressed activities of the lymphoid and epithelial components (lesser area of connective tissue elements and glandular tissue, lesser density of parenchymatous cell elements, lesser counts of immunoblasts and small lymphocytes, and larger area of the medulla) in comparison with animals without chemotherapy.

Effect of Natural and 24-h Illumination on Mesenchymal Stem Cells

We studied the effect 24-h illumination on quantitative and qualitative parameters of the bone marrow cells in Wistar rats. It was shown that desynchronosis reduced the release of nucleated cells from the femoral bone, while melatonin weakened this effect. The number of bone marrow mesenchymal stromal cells was resistant to circadian rhythm disturbances, while proliferation depended on glucose concentration in the medium.

Blood Serum Levels of Proinflammatory Cytokines (IL-1β, 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-1β 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.

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.

Polymorphisms in Genes of Cytokines and Matrix Metalloproteinases Associated With Ischemic Heart Disease in Patients With Type 2 Diabetes

OBJECTIVE To examine associations between ischemic heart disease (IHD) and polymorphisms in cytokine genes (IL-1B, IL-4, IL-6, IL-10, TNFA, VEGF) and matrix metalloproteinase genes (MMP2, MMP3, MMP9) in patients with type 2 diabetes. MATERIAL AND METHODS We studied 232 Caucasian diabetic subjects (33 men and 199 women aged 50-70 years). In 93 patients IHD was verified by treadmill test and/or coronary angiography (86 subjects with stable angina, 19 with previous myocardial infarction). Thirteen polymorphisms localized in the promoters of IL-1B (rs1143627), IL-4 (rs2243250), IL-6 (rs1800795), IL-10 (rs1800872, rs1800896), TNFA (rs361525, rs1800629, rs1800630), VEGF (rs699947, rs3025039), MMP2 (rs243865), MMP3 (rs3025058) and MMP9 (rs3918242) were investigated. RESULTS Prevalence of G-allele and GG-genotype at -308 position of TNFA (rs1800629), as well as C-allele and CC-genotype at position +936 of VEGF (rs3025039) was higher in patients with IHD as compared to patients without IHD (OR=2.0, OR=2.2, OR=2.1, OR=2.4, respectively, all p=0.02). In logistic regression analysis, TNFA -308 A/G and VEGF +936 C/T polymorphisms showed associations with IHD (both p=0.009). These polymorphisms along with age, body mass index, duration of diabetes, low density and high density lipoprotein cholesterol were associated with IHD in multivariate models (p=0.0002 and p=0.00008, respectively). Nine combinations of TNFA -308 GG-genotype and variants of other genes demonstrated associations with IHD (p≤0.002). CONCLUSION The polymorphisms in promoter regions of TNFA (rs1800629) and VEGF (rs3025039) are associated with IHD in patients with type 2 diabetes.

Melatonin—Aluminum Oxide—Polymethylsiloxane Complex on Apoptosis of Liver Cells in a Model of Obesity and Type 2 Diabetes Mellitus

We studied the effects of a melatonin—aluminum oxide—polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.