Functional Phenotype of Alveolar Macrophages Features in Rats with Metabolic Syndrome.

Phenotypic characteristics of alveolar macrophages in the bronchoalveolar lavage fluid as well as their ability to acquire the M1 and M2 phenotypes during in vitro culturing with reprogramming factors were studied in rats with modeled diet-induced metabolic syndrome. A decrease in the number of alveolar macrophages with the M1 phenotype was found in animals with metabolic syndrome. The factors of metabolic syndrome do not affect phenotypic plasticity of cells in culture, but under the action of M2 reprogramming factors, the cells demonstrate a wide range of phenotypic plasticity by the CD80 and CD206 markers. The consistently high level of production of IL-6 and IL-10 by macrophages during culturing under different conditions indicates functional rigidity of the cells, which is probably a consequence of in vivo predetermined functional phenotype of these cells against the background of metabolic disorders.

Intracellular Lipid Levels and Oxidative Stress in Peripheral Blood Mononuclear Cells in Experimental Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus was modeled in Wistar rats by intraperitoneal injection of streptozotocin (25 mg/kg for 5 days), which led to the appearance of the main symptoms of insulin-dependent diabetes. In peripheral blood mononuclear cells isolated by centrifugation on a Ficoll density gradient, the production of ROS and the level of intracellular lipids were evaluated by flow cytofluorimetry. In rats with type 1 diabetes mellitus, an increase in ROS levels in isolated peripheral blood monocytes, but not in the lymphocytic fraction was revealed. Incubation of isolated monocytes in a medium containing 1 mM oleic acid led to a 1.5-fold increase of intracellular lipid levels. After incubation of the lymphocyte fraction in this medium, no differences from the control were revealed. Disorders of carbohydrate and lipid metabolism in type 1 diabetes mellitus leading to an increase of free fatty acids and ROS levels can be detected ex vivo in isolated peripheral blood mononuclear cells.

Hypolypidemic Activity of L-Rhamnopyranosyl-6-O-Methyl-D-Galacturonan, a Polysaccharide Isolated from Birch Leaves (Betula pendula L.).

In male Syrian hamsters fed a synthetic high-fat diet enriched with cholesterol (0.3%), administration of a polysaccharide from birch leaves L-rhamnopyranosyl-6-O-methyl-D-galacturonan (3 g/100 g of diet) resulted in a decrease in total cholesterol levels, mainly due to the LDL fraction, triglycerides, and bile acids in blood serum; the content of triglycerides and cholesterol in the liver also decreased, while excretion of bile acids with feces increased. Thus, the lipid-lowering effect of L-rhamnopyranosyl-6-O-methyl-D-galacturonan is related to its ability to bind bile acids in the intestine and interrupt their enterohepatic circulation.

Insulin Resistance in Experimental Type 1 Diabetes Mellitus.

Experimental type 1 diabetes mellitus (T1DM) was induced in rats by daily intraperitoneal injections of alloxan in a dose of 90 mg/kg for 4 days. For verification of insulin resistance, insulin tolerance test was performed in 2 weeks and the glucose utilization rate constant (KITT) was calculated. The rats demonstrated the main symptoms of T1DM: hypoinsulinemia, hyperglycemia, ketonemia, glucosuria, ketonuria, polydipsia, polyphagia, weight loss, and insulin resistance, as evidenced by a decrease in KITT. The serum content of free fatty acids and triacylglycerols significantly increased. The content of triacylglycerols increased in skeletal muscles and decreased in the liver. A negative linear correlation was found between KITT and triacylglycerol content in muscles. Thus, the development of insulin resistance in experimental T1DM in rats is associated with accumulation of triacylglycerols in skeletal muscles.

Role of H2S in Regulation of Vascular Tone in Metabolic Disorders.

We studied the effect of the H2S donor (NaHS, 1-500 µM) on the contractile responses of isolated aortic smooth muscle segments from rats with metabolic syndrome induced by high-fat, high-carbohydrate diet. It was found that the vasorelaxing effect of NaHS (5-100 µM) decreased in under conditions of MS. The endothelial NO synthase inhibitor L-NAME (100 µM) suppressed the effect of NaHS, while cystathionine-gamma-lyase inhibitor PAG (100 µM) decreased the vasodilating effects of acetylcholine (0.1-100 µM). Application of endogenous NO precursor L-arginine (1 mM) potentiated in the effects of H2S donor NaHS. Thus, the contractile activity of vascular smooth muscles in metabolic syndrome is determined by not only the effect of H2S, but also the influence of NO.

Regulation of Vascular Smooth Muscle Contractions in the Model of Metabolic Syndrome.

Reduced glucose tolerance, hyperglycemia, and imbalance in lipid levels were found in rats with metabolic syndrome induced by a high-fat, high-carbohydrate diet. The contractile responses of intact and endothelium-denuded aortic smooth muscle segments from rats with metabolic syndrome to application of acetylcholine, phenylephrine, sodium nitroprusside, and forskolin were studied by mechanographic method. It was found that endothelial dysfunction develops against the background of metabolic and hemodynamic disorders in metabolic syndrome. It was shown that the regulation of vasoconstrictor reactions of vascular smooth muscles in metabolic syndrome is due to a decrease in Ca2+ entry, mainly voltage-independent, as well as changes in the function of cGMP- and cAMP-activated K+-channels.

Anti-Adhesion Effect of Composite Film Materials Based on Glycoluril-Modified Sodium Carboxymethyl Cellulose.

The aim of the study was to develop composite film materials derived from modified sodium carboxymethyl cellulose and to evaluate their anti-adhesive effects. Materials and Methods: The modified film materials were obtained by dissolving sodium carboxymethyl cellulose (Na-CMC) in an aqueous solution of a modifier (glycoluril) with subsequent homogenization and drying in a vacuum drying oven at room temperature. Physicomechanical parameters of the obtained films were determined using the Instron 3369 universal electromechanical testing machine (Great Britain) equipped with a climatic chamber (300-523 K), improved video extensometer, and the MKC-25 micrometer (Russia). Cytotoxicity of glycoluril-modified film materials derived from Na-CMC was studied by incubating cell cultures of 3T3-L1 mouse fibroblasts directly with extracts from films under study using a colorimetric test. Their anti-adhesion effect was investigated on 40 female Wistar rats by modeling a flat adhesion by inducing abrasion of the cecum and suturing the deserosed surface of the abdominal wall anatomically opposite the abrasion area. The presence of adhesions was assessed on day 8 after the operation. Commercial membrane Seprafilm (USA) was used as a reference sample. Results: It was found that extracts obtained from film materials derived from Na-CMC modified with glycoluril at a concentration of 0.01 and 0.05 wt. % had no cytotoxic effect on the cell culture of mouse fibroblasts 3T3-L1. Flat adhesions were not detected when using Seprafilm. When film materials under study were placed in the abdominal cavity between the injured areas, formation of flat adhesions was not observed or observed in one case out of ten. Conclusion: The obtained films are promising for preventing adhesions as a barrier-type agent. Modifying Na-CMC with glycoluril made it possible to create films that prevent formation of flat adhesions, have improved physical and mechanical properties and no cytotoxic effect.