Vol 11, No 4 (2016)

The article provides an overview of the current knowledge about the immune response in sepsis. Sepsis occurs on a background of development as a systemic inflammatory response, and immunosuppression phenomena. Dysfunction of the immune system is one of the most important parts of the pathophysiology and compulsory process. One of the immunosuppression mechanisms in sepsis is lymphocyte apoptosis. The article describes the main activation pathway of this process including those in neonatal sepsis.

High need for effective bone substitutes and drawbacks of the materials approved for clinical use determine the increasing activity of biomedical research in this area. We have developed gene-activated bone substitutes consisting of a scaffold based on octacalcium phosphate (OCP) and one of the two variants of plasmid DNA carrying either a gene for vascular endothelial growth factor (VEGF) or two genes encoding VEGF and stromal derived factor-1а (SDF-1a). The aim of the study was to evaluate the cytotoxicity of the gene-activated materials and their components, as well as biological activity in vitro. We found that both OCP and gene-activated bone substitutes did not have any cytotoxicity, but reduced the proliferative activity of human bone marrow-derived multipotent mesenchymal stromal cells: material with doublegene construct decreased cell culture doubling rate of 24.3% more compared with the material carrying plasmid DNA encoding only VEGF. Both gene-activated materials led to an increase in therapeutic genes mRNA levels, but the material with double-gene system enhanced VEGF protein production greater. Thus, the gene-activated bone substitutes characterized by the absence of cytotoxic properties and possessed a specific activity increasing expression of the therapeutic genes. However, further studies are needed to detail the identified characteristics and assess the feasibility of the defined biological action in vivo. свойств и обладали специфической активностью в виде увеличения экспрессии терапевтических генов. Однако дальнейшие исследования необходимы для детализации выявленных особенностей и оценки реализуемости биологического действия in vivo.

Tissue engineering provides the opportunity to minimize some possible negative results of the synthetic vascular grafts in long-term follow-up. The choice of the optimal scaffold and cell source for seeding are key conditions to bring properties of vessel substitute to physiological. In some works it is shown that a chitosan-polycaprolactone blend is a suitable biodegradable material for tissue engineering. In this paper we suggest an efficient method to generate of tissue-engineered chitosan-polycaprolactone blends, cellularized by endothelial cells of human cardiac explants. The cells cultured on the blended membranes retain their functional properties: viability and proliferative properties; maintain specific endothelial antigens and synthesis of extracellular matrix. These results suggested that tissue-engineered chitosan-polycaprolactone blends seeded by endothelial cells of human cardiac explants may be potential to development of substitutes for small diameter blood vessels.

Resection of the liver is the main method of treatment in primary and metastatic liver tumors. Frequent complication after extended hepatectomy is acute liver failure, which occurs in 33.83% of cases and may lead to death. The aim of this study is to determine the therapeutic potential of multipotent mesenchymal stromal cells in the treatment of acute liver failure after extended hepatectomy in animal models (rats). The liver mass (before and after 70% hepatectomy), synthetic function of the liver, the level of liver enzymes were measured. The results showed that transplantation of 2.5 mil. of multipotent mesenchymal stromal cells of bone marrow into the inferior vena cava improves liver function and decrease the level of liver enzymes. We observed better recovery of liver mass, and liver functional test (total protein, albumin, alkaline phosphatase, INR, APTT, direct bilirubin) in the experimental group. Thus, multipotent mesenchymal stromal cells have therapeutic effect in treatment of acute liver failure after extended hepatectomy in the experiment. However, more research is needed to understand the mechanisms of therapeutic action of these cells after extended hepatectomy.

Testicular microlithiasis is a random finding on ultrasound testicular examination. Testicular microlithiasis is of particular interest as an informative marker in men with an increased risk of testicular germ cell tumors. Genes KITLG, SPRY4 and BAK1 influence the development of the testes and spermatogenesis, their change results in a significant increase in the risk of testicular germ cell tumors. To determine the genetic factors that determine an increased risk of testicular germ cell tumors in patients with testicular microlithiasis, we investigated the frequency of alleles and genotypes of genes KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876) and BAK1 (rs210138) in groups of fertile male, patients with testicular germ cell tumors and patients with testicular microlithiasis. For KITLG rs995030 we found significant differences in the frequency of the genotype GG in patients with testicular microlithiasis (p = 0.013) and in patients with testicular germ cell tumors (p = 0,0031) compared with the control. For KITLG rs1 508595 revealed significant differences in the frequency of G allele and GG genotype in patients with testicular microlithiasis (p = 0,002 for allele, p = 0,01 for genotype) and patients with testicular germ cell tumors (p = 0.0003 for allele; p = 0,014 for genotype). For BAK1 rs210138 we found significant differences in the frequency of G allele in patients with testicular microlithiasis, compared with the control group (p = 0,03). With a combination of high-risk genotypes study KITLG (rs995030, rs1508595) an BAK1 (rs210138) showed that the combination of these genotypes were significantly more common in patients with testicular germ cell tumors (p = 0,0001) and patients with testicular microlithiasis (p = 0,0053), on compared with the control. We have shown an increase in frequency of genotypes combination for testicular germ cell tumors at 4,6 times (OR: 4,669 [2,172-10,034]), and testicular microlithiasis - 3,3 times (OR: 3,355 [1,471-7,654]).