[Pediatric kidney transplantation: early and long-term outcomes following 1187 procedures]. / Transplantatsiia pochki detiam: neposredstvennye i otdalennye rezul'taty 1187 operatsii.

AIM: To estimate short- and long-term outcomes of pediatric kidney transplants in Russia considering the maximum available number of cases. MATERIAL AND METHODS: Retrospective, observational, multi-center study included data about 1187 kidney transplantation procedures (866 - deceased donor, 281 - living donor and 40 - AB0-incompatible living donor) performed in 1065 patients (age 0-17 years) since 1990 till 2017. Patient and graft survival, causes of recipient deaths and graft losses, as well as, the influence of donor type, blood group incompatibility and recipient age on outcomes were analyzed. Results of redo transplantations (n=131) were also investigated. RESULTS: Annual, 5- , 10- , and 15-year survival of patient was 94, 86, 79 and 69%, respectively; graft survival - 85, 67, 53 and 33%, respectively. Transplantation from related donors including AB0-incompatible cases was associated with 15-30% increase of graft survival (p<0.0001). Up to 23% of children required redo transplantation within 4-5 years after primary procedure and 2/3 of patients - after 10-15 years. There were no significant differences in outcomes after primary and redo procedures: annual, 5-, 10- and 15-year graft survival was 85, 68, 55, 42 and 85, 62, 45, 19%, respectively (p=0.1164). CONCLUSION: It is reasonable to consider the outcomes of transplantations as satisfactory in Russia. However, there is a great potential for improvement. The main problems are high incidence of infectious complications followed by fatal outcomes (41% of all fatal outcomes) and loss of allograft due to primary dysfunction and death of recipients with functioning allografts (19 and 23%, respectively). Primary use of living-related donors for pediatric kidney transplantation seems to be the most effective way to improve both short- and long-term outcomes.

Considerable variations in growth hormone policy and prescription in paediatric end-stage renal disease across European countries-a report from the ESPN/ERA-EDTA registry.

BACKGROUND: Growth retardation in paediatric end-stage renal disease (ESRD) has a serious impact on adult life. It is potentially treatable with recombinant growth hormone (rGH). In this study, we aimed to quantify the variation in rGH policies and actual provided care in these patients across Europe. METHODS: Renal registry representatives of 38 European countries received a structured questionnaire on rGH policy. Cross-sectional data on height and actual use of rGH on children with ESRD aged <18 years were retrieved from the ESPN/ERA-EDTA Registry. RESULTS: In 21 (75%) of 28 responding countries, rGH is reimbursed for children with ESRD. The specific conditions for reimbursement (minimum age, maximum age and chronic kidney disease stage) vary considerably. Mean height standard deviation scores (SDS) at renal replacement therapy (RRT) [95% confidence interval (CI)] were significantly higher in countries where rGH was reimbursed -1.80 (-2.06; -1.53) compared with countries in which it was not reimbursed [-2.34 (-2.49;-2.18), P < 0.001]. Comparison of the mean height SDS at onset of RRT and final height SDS yielded similar results. Among the 13 countries for which both data on actual rGH use between 2007 and 2011 and data from the questionnaire were available, 30.1% of dialysis and 42.3% of transplanted patients had a short stature, while only 24.1 and 7.6% of those short children used rGH, respectively. CONCLUSION: Reimbursement of rGH associates with a less compromised final stature of ESRD children. In many countries with full rGH reimbursement, the actual rGH prescription in growth-retarded ESRD children is low and obviously more determined by the doctor's and patients' attitude towards rGH therapy than by financial hurdles.

[ROLE OF INNATE IMMUNITY FACTORS IN PERIODONTITIS PATHOGENESIS].

Chronic generalized periodontitis (CGP) is a disease of periodontium tissues supporting tooth induced by bacteria, that is characterized by the presence of processes of inflammation with destruction of bone tissue. The knowledge of molecular mechanisms of CGP pathogenesis facilitates creation of the most effective methods of therapy of this disease. Bacterial infection is a primary factor in periodontitis etiology, however is not sufficient for its start and subsequent development. It is known, that bacterial factors induce alocal inflammationreaction and.activate the system of innate immunity through activation of Toll-like receptors (TLR), located on the surface of resident cells and leukocytes. Activation of these cells results in production of pro-inflammatory cytokines and recruitment of phagocytes and lymphocytes into the inflammation zone. In review we examined the known data regarding factors of immune protection of periodontium including cell populations and cytokines, as well as mechanisms of tissue destruction, that support the tooth. Perspectives of therapy are also discussed

[STUDY OF THE ROLE OF INNATE IMMUNITY FACTORS (TLR2, HBD-2, TNF-α, TGF-ß) IN PERIODONTITIS PATHOGENESIS].

AIM: Study of the role of innate immunity factors, namely, expression of TLR2 and HBD-2 genes, as well as TNF-α arid TGF-ß in pathogenesis of periodontium tissue inflammation. MATERIALS AND METHODS: 59 individuals with periodontitis illnesses were included into the study; 15 healthy donors represented the comparison group. Study of the TLR2 and HBD-2 gene expression levels was carried out by rRT-PCR, cytokine production evaluation--by EIA. RESULTS: The results of the study have shown the presence of TLR-mediated disbalance in the innate immunity system in the periodontium tissue during chronic generalized periodontitis. TLR2 gene hyperexpression was accompanied by the reduction of expression of anti-microbial peptide HBD-2, as well as an increase of production of TNF-αand TGF-P by epithelial cells of periodontium mucosa. Conclusion.-The study carried out has shown that disturbance of molecular mechanisms of innate immunity system has an important place in pathogenesis of periodontitis. -

[The sensitivity of mesenchymal stromal cell subpopulations with different times of adhesion property manifestation and derived from hemopoietic organs to growth factors EGF, bFGF, and PDGF].

The action of three growth factors (EGF, bFGF, and PDGF) on mesenchymal stromal cell (MSC) subpopulations from mature bone marrow (BM) and rat embryo liver (EL) was investigated. These cells are plastic-adhesive and have different rates of adhesion (AC1-AC4 subpopulations). The efficiency of colony-formation, the size of colonies, and the number of early osteogenic progenitors with alkaline phosphatase activity in colonies and induced osteogenesis were analyzed. It was shown that EGF increased the number of bone marrow (BM) MSC colonies, but it had no influence on osteogenic differentiation. bFGF suppressed colony formation, but it stimulated both early and late stages of steogenesis. PDGF increased the size and the number of colonies in AC2 and AC3 subpopulations, but it stimulated only the ostegenesis terminal stage. The distinction between MSC subpopulations from two organs were found: MSC from EL had small osteogenic capacities and low sensitivity to grow factors; MSC from BM had no such characteristics. MSC subpopulations with different adhesion properties and from different tissues had compatible sensitivity to growth factors. Thus, these cells have no parent-progeny relationship.

[Efficacy and safety of cyclosporin A withdrawal in children long after kidney transplantation].

AIM: Evaluation of cyclosporine (CSA) withdrawal safety and efficacy in children late after kidney transplantation. MATERIAL AND METHODS: Graft and patient survival was analysed in 30 kidney recipients operated in the central children's hospital in 1991-1999. Fifteen of 30 patients came for follow-up to the Russian Research Center for Surgery where CsA was withdrawn 6.8 +/- 2.7 after transplantation. The other 15 children continued immunosuppression with CsA. RESULTS: Higher graft survival was observed in children in whom CsA was discontinued. CONCLUSION: Discontinuation of cyclosporine late after kidney transplantation results in improvement of graft survival in most of the patients.

[Nonadhesive populations in cultures of mesenchymal stromal cells from hematopoietic organs in mouse and rat].

The study of adhesive properties of multipotent mesenchymal stromal cells evaluated from fibroblast colony-forming units in the bone marrow of adult mice and rats in populations of cells attached and unattached to plastic substrate after 2 h to 7 days in culture demonstrated both similarities and differences. The increase in the fibroblast colony-forming units in the adhesive population peaked on day 7 of in vitro culture in both cases; however, nearly no fibroblast colony-forming units were observed in the nonadhesive population from the mouse bone marrow in this period. Conversely, the number of colonies from the rat bone marrow nonadhesive population on day 7 of culture considerably increased, and this nonadhesive population in long-term culture became the source for subsequent nonadhesive subpopulations containing fibroblast colony-forming units. After 7 days of in vitro culture, the suspension of cells isolated from the liver of 17-day-old rat fetuses also contained a fraction of unattached fibroblast colony-forming units. In the nonadhesive subpopulations from the bone marrow and fetal liver, fibroblast colony-forming units were observed up to day 48 and 30, respectively. Stromal cell precursors of nonadhesive subpopulations from the rat bone marrow featured a period of colony formation reduced to 7 days (i.e., they were formed 1.5-2 times faster compared to the primary culture). The total number of fibroblast colony-forming units from all nonadhesive subpopulations was roughly 6 and 7.4 times that of the adhesive population of the primary culture from the bone marrow and fetal liver, respectively. Considering that the mammalian bone marrow remains the preferred source of mesenchymal stromal cells, using nonadhesive subpopulations in the presented culture system can considerably increase the yield of stromal precursor cells.

[Effects of growth factors on multipotent bone marrow mesenchymal stromal cells].

Multipotent bone marrow mesenchymal stromal cells are progenitors of various cell types capable of long-term self-maintenance. These cells are an adequate model for studying the most important problems in cell biology, such as self-maintenance of stem cells and regulation of their differentiation. Moreover, these cells are a promising resource for regenerative medicine. In this context, isolation of the earliest multipotent mesenchymal stromal cells, their in vitro maintenance in an undifferentiated state, and stimulation of their differentiation in a desired direction appear to be most important. To successfully use the multipotent mesenchymal stromal cells both in fundamental studies and in therapy, it is necessary to modify and standardize the composition of culture medium, replacing blood serum with certain growth factors. These factors have influence on the proliferation and differentiation of most cell types, including multipotent mesenchymal stromal cells. This paper is a review of available data concerning the effects of some growth factors on the multipotent mesenchymal stromal cells of the bone marrow.

[Analysis of sensitivity of stromal stem cells (CFU-f) from rat bone marrow and fetal liver to 5-fluorouracil].

The sensitivity of stromal stem cells (CFU-f) from rat bone marrow and fetal liver to the cytotoxic effect of 5-fluorouracil (5-FU) was compared in vivo and in vitro. Cells from both tissues demonstrated a similar resistance to 5-FU in vitro; however, stromal stem cells from fetal liver proved notably more sensitive to 5-FU compared to marrow CFU-f in vivo. Cells forming colonies of different size were identified in stem cell populations from both tissues. Cells giving rise to small colonies had a higher resistance to 5-FU both in vivo and in vitro.