Patologicheskaia fiziologiia i eksperimental'naia terapiia最新文献

In this review, we present information about a heterogeneity of monocyte subsets based on their unique functional and phenotypic properties. Here we also discuss the search of an optimal technique for the isolation of monocyte subsets as well as the origin of monocyte subsets and their role in inflammation.

It is known that stem and progenitor cells open new possibilities for restoring injured eye tissues. Limbal eye zone, formed mainly by derivatives of neural crest, is the main source of stem cells for regeneration. The current study considers development of innovative technology for obtaining 3D spheroids from L-MMSC. It was shown that under 3D conditions L-MMSC due to compactization and mesenchymal-epithelial transition self-organize into cellular reparative modules. Formed L-MMSC spheroids retain and promote undifferentiated population of stem and progenitor limbal cells, as supported by expression of pluripotency markers - Oct4, Sox2, Nanog. Extracellular matrix synthetized by cells in spheroids allows retaining the functional potential of L-MMSC that are involved in regeneration of both anterior and, probably, posterior eye segment.

The purpose: The influence of high-fat diet (HFD) on trace elements status, adipokine level, and markers of carbohydrate and lipid metabolism in weanling Wistar rats was investigated.

Methods: A total of 20 male 1-months-old Wistar rats divided into two equal groups were used in the present study. The first group of animals obtained a standard diet (STD), whereas animals from the second group (NAFLD) were maintained on high-fat diet containing 10 and 31.6% of total calories from fat, respectively, during 1 month. Fat diet (HFD). Trace element status (using inductively coupled plasma mass spectrometry), serum levels of insulin, adiponectin, and leptin (using enzyme-linked immunosorbent assay), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose (spectrophotometrically), apolipoprotein A1 (ApoA1) and B (ApoB) (using immunoturbidimetric method) were assessed.

Results: It was shown that 1-month HFD feeding resulted in significant increase of EDAT, RPAT, total adipose tissue mass, and adipocyte area. HFD-fed animals were also characterized by a significant increase in circulating leptin levels and leptin-to-adiponectin ratio as compared to the control ones. No significant HFD-related difference in serum lipid spectrum, adiponectin, apolipoproteins, glucose, insulin, and HOMA-IR were revealed. Liver Cu, I, Mn, Se, Zn; EDAT Cr, V, Co, Cu, Fe,I, and RPAT Co, Cu, I, Cr, V, Fe, and Zn were significantly decreased in HFD-fed rats in comparison with the control group levels. Hair Co, Mn, Si, and V levels significantly exceeded the respective control values, whereas Se and I content were decreased in studied animals. At the same time, only serum Cu was significantly decreased in HFD-fed rats.

Conclusion: The interplay between the impaired trace elements metabolism of HFD-fed weanling Wistar rats and disorder of adipokine balance was demonstrated. It is supposed that the altered trace elements status is primary and precedes other metabolic obesity-related disturbances.

Heat shock protein HSP40 family molecular chaperone DNAJB6/MRJ expression has been analyzed in blood cells of patients with atopic dermatitis compared with healthy donors. Severity of disease was estimated according index SCORAD.

Methods: Peripheral blood cells were separated using Percoll density gradient. Purified neutrophils and lymphocytes have been stained with antibodies to the heat shock protein DNAJB6/MRJ. Cells were analyzed using flow cytometry. Real time PCR method has been used to verify the bacterial contamination of the skin of patients with atopic dermatitis. Statistical analysis was performed by ANOVA.

Results: Expression of DNAJB6/MRJ protein has been found to be elevated in all samples of cells obtained from patients with atopic dermatitis. The highest level of the DNAJB6/MRJ protein expression was shown in neutrophils at the acute phase of severe atopic dermatitis. DNAJB6/MRJ protein expression in lymphocytes of patients with atopic patients was less extensive compared with neutrophil level and was shown to be higher at subacute phase of disease. The DNAJB6/MRJ protein expression was found to be statistically significant higher in lymphocytes from atopic patients compared with healthy donors. The bacterial contamination of skin (verified by PCR) was shown to influence the DNAJB6/MRJ protein level in lymphocytes of atopic dermatitis patients.

Conclusion: Expression of the heat shock protein DNAJB6/MRJ was elevated in neutrophils and lymphocytes of patients with atopic dermatitis compared with healthy donors. The highest level of the DNAJB6/MRJ protein was found to be in neutrophils at acute phase of severe atopic dermatitis and gradually decline as continue to the disease.

The purpose: The purpose. Investigate the levels of different classes serum anti-endotoxin antibodies in patients with diabetes mellitus type 1 and 2 and to hold the cluster analysis of the relationship between the individual levels of such antibodies and the concentration of C-reactive protein in the blood.

Methods: We examined 51 patients with diabetes mellitus type 1 and 60 patients with diabetes mellitus type 2. The diagnosis of diabetes mellitus type 1 or type 2 has been delivered in accordance with the criteria of the World Health Organization. The control group included 49 healthy people who have not a history of any chronic disease, and the clinical manifestations of acute diseases were absent at the time of the survey. By sex and age, the control group of healthy people matched to a group of patients with diabetes type 1 and type 2. The concentration of C-reactive protein in the blood and the levels of serum anti-endotoxin antibodies of different classes (A, M and G) was determined by ELISA.

Results: Using cluster analysis revealed that 40.8% of patients with type 1 diabetes increased concentration of C-reactive protein in the blood is associated with a significant reduction of levels of serum anti-endotoxin antibodies classes A, M and G. In 56.7% of patients with type 2 diabetes the high concentration of C-reactive protein in the blood levels of serum anti-endotoxin antibody classes A and M were not significantly different from the normal values, but the levels of serum anti-endotoxin antibodies of class G were significantly increased. The activation of inflammation with a further increase of C-reactive protein in the blood of patients with type 2 diabetes mellitus accompanied by a significant increase in levels of serum anti-endotoxin antibodies classes A and G, and also a tendency to reduce of levels anti-endotoxin antibodies class M.

Conclusion: The results suggest about the relationship between low-intensity inflammation and immune response to enterobacterial endotoxins in patients with diabetes mellitus type 1 and 2.

The purpose of this paper is to examine the levels of cytokines in the lymph involved in the pathogenesis of breast cancer.

Methods: Breast cancer was induced by introducing n-methyl-N-nitrosourea rats Wistar breed. Some of the animals subjected to surgery alone or chemotherapy alone (cyclophosphamide, methotrexate, 5-fluorouracil). Some animals combine both types of therapy, as well as a separate group to the administration of chemotherapy added Panagene drag presenting a fragmented DNA. To investigate the concentration of cytokines used in lymph test system Bio-Plex Pro Rat Cytokoness 24-Plex Assay (Bio-Rad, USA).

Results: In rats with breast cancer content of most studied cytokines such as, IL-1b, IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, IL-17A, MIP-1a, MIP-3a, RANTES, TNF-a, MCP-1 was significantly higher than in intact animals. Surgical removal of the tumor resulted in a significant decrease in the content in the lymph as a pro-inflammatory cytokine. Comparative performance study cytokine content in the lymph after tumor removal from intact animals showed that the content of cytokines such as IL-10, IL-18, GRO / KC, RANTES were significantly higher in the control animals group. Conducting chemotherapy has led to a significant decrease in the content of IL-1b, IL-4, IL-6, IL-7, IL-10, MIP-1a, MIP-3a, RANTES in rat breast cancer lymph. Comparative study of cytokine content in the lymph operated animals after the administration of chemotherapy and Panagene revealed that most of the content indicators cytokines such as IL-5, IL-6, IL-7, IL-10, IL-13, IL-17A, IL- 18, GRO / KC, IFNg, MIP-3a in the lymph was higher after administration of the drug Panagene.

Conclusion: In a comparative study cytokine profile lymph Wistar rats found that cytokine content depended on the therapy in animals with induced breast cancer. Lymph cytokine levels may serve as a diagnostic criterion for tumor growth, as well as the predictor of the effectiveness of the therapy and the risk of metastasis of breast cancer.

As a component of various enzymes, it refers to copper essential trace elements, but the excessive consumption of the metal leads to the development of the pathogenic effects of xenobiotics on the functional condition of the cardiovascular system. However, the works devoted to the study of the effectiveness of prophylactic calcium in a copper toxicity, is not in the current literature.

The purpose: study the effect of long-term toxicity of copper on the functional state of the cardiovascular system and its reactivity in experimental hypercalcemia.

Methods: Experimental hypercalcemia model was created by forming a pilot hypervitaminosis D, by introducing «Akvadetrim» atraumatic preparation through a probe into the stomach in the dose 3000 IU (0.2 ml) / 100 g of body weight for 30 days. Chronic copper poisoning model created by intragastric administration of copper sulfate solution at a dosage of 20 mg/kg (in terms of metal) for 30 days, daily one time a day. The study of the functional state of the cardiovascular system is to determine the mean arterial pressure, specific peripheral vascular resistance, stroke index, cardiac index, the reactivity of the renin-angiotensin system and adrenoreactivity cardiovascular system.

Results: The experimental study revealed that long-term copper poisoning leads to the development of hypertension due to an increase in total peripheral vascular resistance, along with the marked decline in the pumping function of the heart. Experimental hypercalcemia simulated by intragastric administration of vitamin D promotes more pronounced toxic effects of copper sulfate on the cardiovascular system.

Conclusion: Copper poisoning of the body is characterized by the development of hypertension and the condition of artificial hypercalcemia potentiates the cardiotoxic effects of copper.

Erythrocytes are prospective carriers of wide range of medicines and other biologically active agents. Main peculiarity and advantage of erythrocytes as carriers of medicines is their absolute bio-compatibility and ability for long circulation in an organism. While growing old these cells undergo natural process of biodegradation. Relatively inactive endocellular environment protects carried medicine from being inactivated by different endogenous factors. At the present time different methods of loading medicines in erythrocytes are used: electroporation, induced endocytosis, osmotic pulse hematolysis, hypotonic hematolysis. Most of these methods are based on the ability of these cells for reversible deformation of the surface without changing area of surface. Introduction of medicines in erythrocytes can be conducted in natural way as a result of their sorption on cell membrane. Different medicines can be used as the objects for targeted transport: antibiotics, antineoplastic drugs, corticosteroids, peptides, enzymes etc. extracorporeal pharmacotherapy with use of erythrocytes as carriers can be applied in the treatment of different diseases. Range of used medicines and provided possibilities is quite wide at a present time, but further development of this direction is very prospective. The aim of the authors was to outline a common concept of the potential of erythrocytes as universal transportation means of medicines for therapy of different pathological conditions.

To investigate the consequences of the endothelium dysfunction caused by the experimental hyperhomocysteinemia.

Methods: The experiment included the similar aged 42 white non-pedigree male rats with average weight of 150 grams. The rats were divided in two groups each of these having 21 species. Hyperhomocysteinemia was induced in experimental rats by intraperitoneal injection of 0,1 mmol homocysteine per 1 gr of weight once a day during 14 days. The equal intraperiotenal dose of the physiological solution was injected to the rats of the control group. The level of homocysteine was determined in the blood serum with high-yield liquid chromatography (HYLC), the content of IFNg, TNFa, IL-17A с was measured with the system of multiplex analysis FlowCytomix 5 plex (BMS826FF) combined with Simplex Kit (BMS8635FF) of appropriate analyts for «Bender Medsystems» rats (Austria). Coagulation indices were determined in the blood plasm of subclavian vein. TF expression of tissue factor was estimated with immune histochemical method.

Results: Fivefold increase of endothelin level and decrease of nitrates and nitrites levels were found in rats with hyperhomocysteinemia. Expression of tissue factor, shortening of activated partial thromboplastin and thrombin times, increase of soluble fibrin monomeric complex level, significant increase of tumor necrosis factor and interferon gamma levels were identified in endothelial cells of myocardial vessels.

Conclusion: Thus, experimental hyperhomocysteinemia (HHC) proved to be accompanied by expressed endothelium dysfunction which is marked by thrombogenic activity of blood as well as endothelium and cytokine level increasing.

Subject: High-density lipoprotein (HDL) is highly heterogeneous in function, structure, and composition. Components of HDL can be assayed using various techniques, including LC/MC approaches. The purpose of this study was to develop a novel method for the analysis of the HDL lipidome. Since phospholipids represent a major bioactive lipid component of HDL, the phosphosphingolipidome of major normolipidemic HDL subpopulations was characterized in this study.

Methods and results: The article describes the methodology used for the analysis of the HDL lipidome. Based on existing methods of lipidomic analysis, an original method of analyzing lipidome of HDL by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS/MS) was developed. This technique was used to analyze the lipidome of five normolipidemic HDL subpopulations.

Conclusion: The developed method allowed to identify and quantify 162 individual molecular lipid species in five normolipidemic HDL subpopulations across nine lipid subclasses, including 23 phosphatidylcholine, 22 sphingomyelin, 9lysophosphatidylcholine, 25 phosphatidylethanolamine, 17 phosphatidylinositol, 11 phosphatidylglycerol, 24 ceramide, 18 phosphatidylserine, and 13 phosphatidic acid species.