Based on clinical practice, some patients with lipid metabolism disorders (LMD) are resistant to lipid-lowering therapy (LLT) — in such patients, taking optimal doses of LLT drugs does not reduce levels of cholesterol and its fractions to target levels and using LLT at higher doses is associated with increased odds of adverse events. To optimize the treatment, 58 patients with ischemic heart disease with LMD resistant to LLT were examined. The patients were divided into two groups: in the main group, 29 patients received laser therapy and unloading therapeutic gymnastics; in the control group, 29 patients continued to take their usual medications. The obtained results showed a significant lipid-lowering effect of the treatment in the main group: we observed a significant decrease in total cholesterol (by 27.7%, p < 0.01) as well as low-density lipoprotein cholesterol (by 34.7%, p < 0.01), a significant increase in high-density lipoprotein cholesterol (28.1%, p < 0.01), a significant decrease of atherogenic coefficient (by 50.2%, p < 0.01) and in the levels of triglycerides (by 49.6%, p < 0.01).  At the same time, no significant positive changes in lipid profile were observed in the control group. In patients of the main group, tolerance to physical activity increased significantly, with statistically insignificant changes in the control group accordingly.
VIEWS 114
Microtia is a combined congenital malformation with the prevalence of one case per 10,000–15,000 newborns, which accounts for 50% of all congenital malformations. Treatment of microtia is a challenging task. Numerous solutions have been proposed, however, none of these options guarantee good functional and aesthetic outcome. High hopes for solving the problem are placed on advances in reconstructive surgery. The study was aimed to determine the possibility of using advanced biocompatible endoprostheses manufactured using the tissue engineering technologies. Two closely related male 2-year-old minipigs of the Sus salvanius breed underwent implantation of bioengineered implants manufactured by combined 3D bioprinting with application of the collagen solution containing autologous cartilage tissue cells under the temporal fascia. The samples were collected 3 months later. Histological examination and immunohistochemistry showed that the implanted endoprosthesis initiated the development of regenerated connective tissue and its own vasculature in 100% of cases, thereby ensuring cell viability and integrity of biological structures; furthermore, no facts of the endoprosthesis rejection or resorption were reported. We have concluded that the developed implant manufacturing method is promising and can provide the basis for creation of domestic porous ear implants based on biocompatible polymeric materials, hydrogels, and autologous cellular material. It is necessary to further test the auricular implant using biological models.
VIEWS 167
The oxidative stress associated with ischemic stroke is a major factor damaging the nervous tissue. Thyroid hormones have a significant effect on the body’s redox status, however, the impact of their derivatives, thyronamines, considered as potential neuroprotectors, on the characteristics of lipid peroxidation (LP) is not clearly understood. The study was aimed to assess the impact of the Т0АМ thyronamine synthetic analogue on the main LP indicators in the model of acute cerebral ischemia. Permanent ligation of the right common carotid artery was performed to simulate acute cerebral ischemia in white rats. The animals were divided into two groups: the control group receiving no treatment and the experimental group, to which the Т0АМ thyronamine synthetic analogue was intraperitoneally administrated (75 mg/kg of the rat’s body weight). After 24 h the rat was decapitated, and the cerebral cortex tissue was extracted for biochemical analysis. The following LP indicators were determined by spectrophotometry: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx). When administering the Т0АМ thyronamine synthetic analogue, a significant (2-fold) decrease in MDA levels was observed in the ischemic hemisphere (р = 0.022), along with the 2.49-fold increase in the GPx activity in the brain tissue (р = 0.004) of the intact hemisphere and the 2.65-fold increase in its activity (р = 0.021) in the ischemic hemisphere, as well as the 1.23-fold increase in SOD activity in the ischemic hemisphere (р = 0.042). The Т0АМ thyronamine synthetic analogue has a great potential in terms of activation of the antioxidant protection mechanisms in the cerebral cortex of white laboratory rats under conditions of acute hemispheric ischemia.
VIEWS 153
Lymphopenia is a condition in which there are lower than normal counts of lymphocytes in the blood. Combination of lymphopenia and prolonged exposure to low temperatures leads to a reduction of adaptive resources, increasing risks of chronic inflammatory processes and secondary environmentally induced immunodeficiencies. The aim of the study was to compare characteristics of immune reactivity in response to cold exposure depending on background level of lymphocytes. Changes in hematologic and immunologic parameters in 203 participants before and immediately after short-term cold exposure were studied. Measurements included skin temperature (forehead, backside of palm), blood pressure, heart rate, leukogram, and hemogram. Levels of ferritin, lactoferrin, transferrin, interleukin-6, interleukin-1β, TNFα, erythropoietin, and irisin were determined using the enzyme immunoassay method. Apoptosis and necrosis of lymphocytes were assessed by flow cytometry analysis using AnV/PI double staining assay. Regardless of the background level of lymphocytes in peripheral blood, same-type responses to short-term cold exposure were observed in cardiovascular system as well as in irisin and ferritin levels, providing an evidence of activating thermoregulation and thermal homeostasis mechanisms. Lymphopenia is associated with a decrease in activity of nonspecific defense - in response to cold exposure there were no changes in level and functional activity of circulating neutrophil granulocytes that can increase the risks of chronicization of infectious processes in this group.
VIEWS 145
The onset and progression of various disorders, including chronic urticaria, are associated with stress. The gut-brain-skin axis is used to describe correlations among the nervous system, gastrointestinal tract states and systemic and skin inflammation. We have summarized inflammatory and immune mechanisms underlying chronic urticaria and stress in the context of the gut-brain-skin axis. The study was aimed to show the relationships between substance P, the neurotransmitter, and diamine oxidase, the enzyme disrupting histamine in the gut of patients suffering from chronic urticaria. A total of 165 adults aged 18–68 were enrolled; 97 patients had chronic urticaria, the comparison group was formed of 68 nominally healthy individuals. ELISA (Cloud-Clone Corp; China) was used to simultaneously estimate serum levels of substance P, diamine oxidase, and histamine. We revealed a significant positive correlation (ρ = 0.5; p < 0.05) between substance P and diamine oxidase in patients with chronic urticaria and in the comparison group, which confirmed the existence of the gut-brain-skin axis. The paper provides theoretical background and new targets for treatment of chronic urticaria. The possibility of prevention and treatment of these disorders by modulation of gut microbiota is discussed, the place of diet and the lifestyle modification contributing to improvement of general health are determined.
VIEWS 118
Today, the cell-based technologies are one of the instruments used for the cartilage tissue repair. Creation of a universal hypoimmunogenic cartilage tissue graft from the differentiated derivatives of induced pluripotent stem cells (iPSCs) might solve the problem of the lack of the cartilage cell product. However, currently there is little data on immunogenicity of such tissue-engineered preparations. The study was aimed to create a cartilage implant from the differentiated derivatives of the B2M-deficient iPSCs and assess its immunogenicity. The previously developed protocol was used to ensure differentiation of both wild-type and B2M knockout iPSCs into chondrocyte-like cells. After quality control of the resulting cell lines by conducting polymerase chain reaction and immunocytochemical assessment, the resulting cell lines were co-cultured with the peripheral blood mononuclear cells of a healthy donor. When co-cultivation was over, activation and degranulation of CD8+ T cells was assessed by flow cytometry analysis based on the CD69 and CD107a expression on the cell surface, respectively. The iPSC-derived chondrocytes expressed the cartilage tissue markers. Flow cytometry analysis revealed no substantial differences in immunogenicity between the derivatives of wild-type and B2M knockout iPSCs, as well as from the cartilage tissue cells of a healthy donor. Immunogenicity of chondrocyte-like cells was higher than that of hypoimmunogenic non-edited iPSCs. The B2M knockout iPSCs demonstrated a trend towards greater activation of CD8+ T cells. Thus, the B2M knockout in the iPSC-derived chondrocytes had no significant effect on the tissue immunogenicity. It is necessary to further edit the genes encoding MHC II and CD47 to obtain a less immunogenic product.
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