bluuebunny/crossref_metadata_2025_split huggingface dataset:
The comparative study of chondrogenic differentiation of mesenchymal stromal cells allocated from different sources
Authors: Basok Yu. B. , Grigoriev A. M. , Kirsanova L. A. , Vakhrushev I. V. , Tsvetkova A. V. , Gryadunova A. A. , Yarygin K. N. , Sevastianov V. I. 
Published: May 2019

Introduction. As an alternative to autochondral transplantation, variants of chondrocyte replacement with mesenchymal stromal cells (MSCs) were considered, since these cells are present in all organs and tissues of human body and possess multilinear potential for differentiation. A number of studies demonstrate that the ability for chondrogenic differentiation of MSCs from different tissues varies, however, those studies are few and controversial. In accordance with the ethical principles and the technical ease of obtaining, adipose tissue, Wharton’s jelly (stroma) and dental pulp are the most attractive sources of MSCs for tissue engineering.Aim: to compare the chondrogenic potential of MSCs allocated from adipose tissue, Wharton’s jelly of the umbilical cord, and human deciduous teeth pulp cultured in the composition of microspheres (pellets).Materials and methods. The phenotype of primary cultures of MSCs was studied via flow microscopy. Chondrogenic differentiation was performed with 3D-culture in microspheres in the presence of TGFβ1 for two weeks under standard conditions. Human chondroblasts were used as a positive control. Cell viability was determined by fluorescent staining. Morphological study was performed using histological and immunohistochemical staining methods.Results. Cultures of MSCs from all sources had similar phenotypes CD29+, CD34–, CD44+, CD49b+, CD45–, CD73+, CD90+, HLADR. In the mass of living cells in microspheres only singular dead cells were visualized. A significant production of extracellular matrix (ECM) was observed in the chondroblast and adipose tissue microspheres, whereas in the microspheres of dental pulp and umbilical cord stroma derived MSCs, no significant ECM was detected. Among the MSCs, the highest production of collagen and glycosaminoglycans (GAG) in the ECM was observed in the microspheres of adipose tissue-derived MSCs, and the lowest production – in the microspheres of dental pulp-derived MSCs. Conclusion. A histological analysis of all microspheres after 14 days of culturing in the chondrogenic medium revealed the signs of differentiation in the chondrogenic direction, a progressive increase of the ECM produced by cells, and the presence of total collagen and GAG in it. Of all the MSCs studied, the greatest chondrogenic potential in vitro (the intensity of development of ECM components) is possessed by the adipose tissue-derived MSCs.
The cyclosporine transdermal transfer possibility study on model systems
Authors: Kuznetsova E. G. , Kuryleva O. M. , Salomatina L. A. , Belov V. Yu. , Sevastianov V. I. 
Published: May 2019

Aim: to develop the emulsion transdermal therapeutic system (TTS) of cyclosporine and the research of its diffusion from TTS.Materials and methods. The quantitative evaluation of cyclosporine in model media was performed on liquid chromatograph Agilent 1100 G1311 with spectrophotometric detector G1315B (Germany). For the production of the emulsion matrix, the Heidolph DIAX900 disperser (Germany) and the ultrasonic homogenizer Hielscher UIS250V (Germany) were used. The cyclosporine diffusion from TTS through Strat-M membrane (25 mm in diameter, Merck Millipore) was studied using Copley diffusion analyser (Great Britain).Results. Using the developed method of micro-HPLC, it was established that the amount of cyclosporine passed through the Strat-M membrane over 24 hours from 10 sm2 TTS, containing 173 mg of the substance, was 5.9 mg. The estimated blood concentration is ~ 50 ng/ml which corresponds to the therapeutic maintenance blood concentration during organ transplantation (50–75 ng/ml).Conclusion. The model studies demonstrate the possibility of the cyclosporine transdermal transfer.
Adhesion, proliferation and viability of human umbilical vein endothelial cells cultured on the surface of biodegradable non-woven matrices modified with RGD peptides
Authors: Antonova L. V. , Silnikov V. N. , Khanova M. Yu. , Koroleva L. S. , Serpokrilova I. Yu. , Velikanova E. A. , Matveeva V. G. , Senokosova E. A. , Mironov A. V. , Krivkina E. O. , Kudryavtseva Yu. A. , Barbarash L. S. 
Published: May 2019

Tissue engineering is a promising area for the production of small-diameter vascular grafts. In recent years, a number of strategies have been developed to make the polymer surfaces of vascular prostheses capable to selectively adhesion of endothelial cells. The arginine–glycine–aspartic acid (RGD) sequence (a cell adhesion site that is present on many extracellular matrix proteins) is the promising target for modification. The efficiency of attachment of endothelial cells can be influenced both by the structure of RGD peptide and the extent of linker group.Aim: to determine the optimal method for modification of non-woven matrices of polyhydroxybutyrate/ valerate and polycaprolactone (PHBV/PCL) by RGD-peptides leading to the increasing of adhesion, viability and proliferation of endothelial cells.Materials and methods. Electrospinning was used to produce 4 mm diameter tubular polymer matrices from PHBV/PCL. Modification of surface of polymer scaffolds was performed using 4,7,10-trioxa-1,13-tridekandiamin, hexamethylenediamine, glutaraldehyde, ninhydrin, ascorbic acid, a cyclic peptide c [RGDFK], RGDK, AhRGD. The quality of modification was assessed by ninhydrin test and determination of arginine-containing peptide. The structure of the surface of matrices before and after modification was studied by scanning electron microscopy. Adhesion, viability and proliferation of Human umbilical vein (HUVEC) endothelial cells cultured for 7 days on the surface of matrices in the presence of RGD and without one were examined using fluorescence and laser scanning microscopy after the cells were pre-stained with fluorescent nuclear dyes (ethidium bromide and Hoechst 33342), and also by special kits for proliferation assessment (Click-iTTM Plus EdU Alexa FluorTM 488 Imaging Kit).Results. RGD peptides bound to the matrix surface via a long linker (4,7,10-trioxa-1,13-tridecanediamine) were characterized by the increased bioavailability and activity. High level of cell adhesion, viability and proliferation were noted on the surface of RGDK and c[RGDFK] modified matrices, whereas their paired analogues with a short linker (hexamethylenediamine) showed low results of cellular viability even against satisfactory cell adhesion.Discussion. Non-woven matrices based on PHBV/PCL and modified using 4,7,10-trioxa-1,13-tridecanediamine showed better results in case of adhesion of HUVEC and subsequent preservation of cell viability and proliferation. RGD-containing peptides of RGDK and c [RGDFK] were more tropic to endothelial cell receptors.
Therapeutic efficacy of intra-arterial administration of induced pluripotent stem cells-derived neural progenitor cells in acute experimental ischemic stroke in rats
Authors: Namestnikova D. D. , Gubskiy I. L. , Salikhova D. I. , Leonov G. E. , Sukhinich K. K. , Melnikov P. A. , Vishnevskiy D. A. , Cherkashova E. A. , Gabashvili A. N. , Bukharova T. B. , Burunova V. V. , Fatkhudinov T. Kh. , Chekhonin V. P. , Gubsky L. V. , Kiselev S. L. , Goldstein D. V. , Yarygin K. N. 
Published: May 2019

Aim. Neural progenitor cells (NPC) are used for the development of cell therapies of neurological diseases. Their stereotaxic transplantation in the middle cerebral artery occlusion (MCAO) model imitating ischemic stroke results in symptom aleviation. However, exploration of less invasive transplantation options is essential, because stereotaxic transplantation is a complex procedure and can be applied to humans only by vital indications in a specialized neurological ward. The aim of the present study was to evaluate the efficacy of cell therapy of the experimental ischemic stroke by the intra-arterial transplantation of NPC.Materials and methods. NPC for transplantation (IPSC-NPC) were derived by two-stage differentiation of cells of a stable line of human induced pluripotent stem cells. Stroke modeling in rats was carried out by transitory 90 min endovascular MCAO by a silicon-tipped filament. NPC were transplanted 24 hours after MCAO. Repetitive magnetic resonance tomography of experimental animals was made with the Bruker BioSpin ClinScan tomograph with 7 Tl magnetic field induction. Animal survival rate and neurological deficit (using mNSS standard stroke severity scale) were evaluated at the 1st (before IPSC-NPC transplantation), 7th and 14th day after transplantation. Histological studies were carried out following standard protocols.Results. Intra-arterial transplantation of 7 × 105 IPSC-NPC in 1 ml at a constant 100 l/min rate in case of secured blood flow through the internal carotid artery did not cause brain capillary embolism, additional cytotoxic brain tissue edemas or other complications, while inducing increase of animal survival rate and enhanced revert of the neurological deficit. IPSC-NPC accumulation in brain after intra-arterial infusion was demonstrated. Some cells interacted with the capillary endothelium and probably penetrated through the blood-brain barrier.Conclusion. Therapeutic efficacy of the systemic, intra-arterial administration of NPC in ischemic stroke has been experimentally proven. A method of secure intra-arterial infusion of cell material into the internal carotid artery middle in rats has been developed and tested.
Gender aspects of incidence of antibody-mediated rejection and allograft vasculopathy events after heart transplantation
Authors: Koloskova N. N. , Poptsov V. N. , Zakharevich V. М. , Muminov I. I. , Mozheyko N. P. , Gichkun O. E. , Nikitina Е. А. , Cvan V. S. , Khalilulin T. A. , Zakiryanov A. R. , Shevchenko A. O. 
Published: May 2019

Abstract. Despite improvements in immunosuppressive therapy, antibody-mediated rejection (AMR) remains one of the most important risk factors for poor prognosis for survival of recipients, cardiac graft dysfunction, and cardiac allograft vasculopathy (CAV) after heart transplantation.Aim: to assess the incidence of case of antibodymediated rejection and cardiac allograft vasculopathy depending on the gender of the patients who underwent heart transplantation in our Center from January 2010 to December 2017.Methods. The median observation was 42 months. The study comprised 606 patients (84 [14%] women) who underwent heart transplantation in 2010 to 2017. We analyzed all the episodes of antibody-mediated rejection, which were diagnosed by the results of endomyocardial biopsies.Results. We comparing the total incidence of antibody-mediated rejection and we are found significant differences among men and women who underwent heart transplantation (p < 0.05), the survival rate during the first year after heart transplantation was 95 and 92%, respectively. The incidence of antibody-consistent rejection was significantly higher among women who had a history of pregnancy and/or use of mechanical circulatory support systems (UNOS status 1A) in the pre-transplantation history (p < 0.05), and we also found significant differences in the incidence of cardiac allograft vasculopathy in women diagnosed with AMR (p < 0.05). The survival rate among women within a year after the diagnosis of AMR is 83% compared to 96% of the recipients free from AMR.Conclusions. Women are at higher risk for AMR after heart transplantation and it increases their risk for cardiac allograft vasculopathy. Females recipients may more frequent myocardial control biopsies and a personalized approach in prescribing immunosuppressive therapy. Women-recipients of transplanted heart should undergo These measures will help to identify in time the development of antibodymediated rejection and reduce the incidence of cardiac allograft vasculopathy after heart transplant.
Pharmacoeconomic analysis of everolimus immunosuppressive therapy for <i>de novo</i> kidney transplant recipients in Russia
Authors: Avxentyev N. A. , Derkach E. V. , Prokopenko E. I. 
Published: May 2019

Currently, patients after kidney transplantation can receive mycophenolate mofetil (MPM), mycophenolic acid (MPA), cyclosporine (CSA) and tacrolimus (TAC) through the Federal High-cost Nosologies Program (VZN) in Russia. Use of everolimus (EVL) in combination with a reduced dose of calcineurin inhibitors has some advantages over the current practice of immunosuppressive therapy that is financed through VZN.Aim: to conduct a comprehensive pharmacoeconomic research of using EVL for immunosuppressive therapy of adult de novokidney transplantation recipients in comparison with the current immunosuppressive therapy practice that is covered by the VZN Program in the Russian Federation.Materials and methods. According to the latest clinical data, effectiveness of immunosuppressive therapy schemes based on EVL and MPA is comparable, which allows to use ‘cost minimization’ method for pharmacoeconomic research. We also performed budget impact analysis of the VZN Program expenditures for a period of 2020–2022.Results. The three-year medication costs of using EVL-based immunosuppressive scheme were 502,785 RUB, which was 508,493 RUB (50.3%) less than medication costs of using MPA-based schemes that are covered by the VZN Program in current practice. The inclusion of EVL to the VZN Program will reduce its costs by 90 million RUB during the first year (2020), by 181 million RUB – during the second year (2021), and by 262 million RUB during the third year (2022). In three years VZN Program costs could be reduced by 533 million RUB (48.6%).Conclusion. Use of EVL is a cost-saving approach for immunosuppressive therapy of adult de novo kidney transplant recipients, compared to MPA-based schemes, that are covered by the VZN Program in current practice in Russia.
Survival analysis of patients in the waiting list for kidney transplantation in terms of competing risks
Authors: Vatazin A. V. , Zulkarnaev A. B. , Stepanov V. A. 
Published: May 2019

Aim: to analyze the survival of patients on the waiting list for kidney transplantation and the results of transplantation depending on the duration of waiting.Materials and methods. We performed a retrospective observational analysis that included 1,197 patients on the waiting list. The end point was exclusion from the waiting list (WL). The causes for exclusion (death, exclusion due to deterioration of the comorbid background or transplantation) were considered in terms of competing risks.Results. In total, 72.5% of patients reached the end point: 21.1% of them died, 11% were excluded, and 40.4% underwent transplantation. Kaplan–Meier estimate showed that cumulative risk of death was 80.4% [95% CI 77.9; 88.6], of exclusion was 77.9% [95% CI 65.4; 88.2], of transplantation was 63.6% [95% CI 58.3; 69] after 10 years on the waiting list. However, such an assessment cannot be directly interpreted as a prediction of the relevant event risk of occurrence for the patient in the WL, because it does not take into account competing events. According to a balanced assessment of the competing risks (Fine and Gray estimate), cumulative incidence was 30.9% (95% CI 27.7; 34.2) for death, 18.2% [95% CI 15.5; 21.1] for exclusion and 49.4% [95% CI 46; 52.6%] for transplantation after 10 years on WL. The probability of transplantation was significantly higher than the risk of death up to and including 5 years of waiting (incidence rate ratio – IRR 1.769 [95% CI 1.098; 2.897]). When waiting 7 to 8 years, the probability of transplantation was less than the risk of death: IRR 0.25 (95% CI 0.093; 0.588; p = 0.0009). Of the 483 recipients, 61 died and 119 returned to dialysis. The risk of graft loss after 10 years was 68.5% [95% CI 57.5; 79.1] and the risk of death of a recipient with a functioning graft was 48.3% [95% CI 34.7; 63] according to Kaplan–Meier estimate. The cumulative incidence of the method was 30.8% [95% CI 23.3; 38.5%] and 55.7% [95% CI 46.6; 63.5%] according to Fine and Gray estimate, respectively. The risk of death after transplantation increases significantly when waiting for more than 6 years – IRR 4.325 [95% CI 1.649; 10.47], p = 0.0045 relative to a shorter waiting period. With an increase in the waiting period, the comorbid background (CIRS scale) deteriorates significantly, even adjusted for the initial patient condition: the partial correlation r = 0.735; p < 0.0001.Conclusion. 1. In the context of competing risks, the Fine and Gray estimate gives a more balanced risk assessment compared to the Kaplan–Meier method. 2. Increasing the waiting time for transplantation significantly increases the risk of death of the candidate on the waiting list and reduces the probability of transplantation, as well as increases the risk of death of the recipient after transplantation. Apparently, this is mainly due to the deterioration of the comorbid background.
Criteria for diagnosis of humoral rejection using the method of 2D-speckle-tracking echocardiography
Authors: Tkhatl L. K. , Stavenchuk T. V. , Kosmachova E. D. , Pashkova I. A. 
Published: May 2019

Aim:to identify predictors of humoral rejection at different stages using non-invasive methods of 2D-speckletracking echocardiography, to determine the correlation with immunological changes.Materials and methods.The study was conducted on the basis of Regional Clinic Hospital of Krasnodar from 2010 to 2017. The analysis of 181 heart recipients was performed. 5 groups were allocated due to the crisis of humoral rejection and the identified antibodies to donor leukocyte antigens (HLA antibodies): group 1 (n = 10) – DSA and humoral rejection, group 2 (n = 7), patients with non-DSA and humoral rejection, group 3 (n = 17) – patients with antibodies to HLA, no humoral rejection, group 4 (n = 11), humoral crisis of rejection, with no identified HLA antibodies, group 5 (n = 87) – patients do not have antibodies to HLA and signs of both humoral and cellular rejection according to EMB. Recipients were carried out endomyocardial biopsy, immunological study, 2D-speckle-tracking echocardiography, statistical methods.Results.The diagnostic criteria for a humoral rejection is greater than 1 degree are global peak systolic strain or strain rate of left ventricle (GLPSLV) – 9.94 ± 1.37% (the sensitivity was 86.2%, specificity – 90.4%); radial systolic strain (RadSLV) of 19.36 ± 3.66% (sensitivity was 75.8%, specificity – 84.5%); circumferential systolic strain (CiRSLV) – 17.83 ± 4.79% (sensitivity was 78.6%, specificity – 84.4%); the twisting of the left ventricle (twist) – 8.90 ± 1.85% (sensitivity – 66.7%, specificity – 94.2%), p < 0.001. When considering indicators GLPSLV and longitudinal peak strain of the right ventricle (GLPSRV) in the diagnosis of humoral rejection sensitivity increases to 91.9%, specificity increases to 94.6%, p < 0.001.Conclusion.GLPSLV has greater sensitivity at the stage of subclinical changes. It is more significantly reduced with increasing degree of rejection associated with episodes of rejection in comparison with other parameters and deformation mechanics. The interrelation between histological and immunological changes and impaired myocardial deformation. The proposed diagnostic algorithm will predict humoral rejection.
Issues and perspectives of building a regional system of donor services (on the example of Nizhny Novgorod region)
Authors: Romanov S. V. , Abaeva O. P. , Alexandrova O. Yu. , Smirnova G. Yu. 
Published: May 2019

Aim: to determine the perspectives of development a regional system of donor services (on the example of Nizhny Novgorod region) based on analysis of current results of its activity.Materials and methods. Protocols of the donor’s initial examination, acts of organ removal for transplantation, questionnaires of 266 doctors of donor bases in the region. Research methods: sociological, statistical.Results. The efficacy of the system of collaboration between the participants of organ donation existing in Nizhny Novgorod region is mainly determined by the activity of doctors on donor bases. According to the results of the questioning of doctors, the most significant factor determining their inclination to collaborate with the Center of organ donation is the direction by the administration of the medical organization (59,3 ± 3,0%). Only 11,1 ± 1,3% of the interviewed doctors stressed their understanding of the importance of the development of organ transplantation programs. As a result, the number of hospitals actually reporting the presence of donors was a half of the number established by the local administration of medical services in 2009. This indicator decreased more than 50% by 2017. During the period of 2009–2017, 488 calls of donor services were registered, while 354 calls ended up being ineffective mainly due to low level of qualification among the specialists of donor bases. During the examined period, there were registered 83 posthumous removals of donor organs with the death of the subjects being mainly (87,6 ± 3,4%) caused by an infarction of cerebral blood circulation. The losses of the donor resource resulted from inability to receive organs from persons who died as a result of injuries due to the rejection of their relatives (49 cases).Conclusion. Optimization of the use of the donor resource of the region is possible only if the development of the organ donation program is promoted at the level of the territorial public health authority. In the case of solving this issue, it is hypothetically possible for the region to achieve an indicator of donor activity of 25 per 1 mln. person.
Analysis of potential donors pool in Moscow region and cases of a removal internal organs for transplantation subjected to medical research in 2017
Authors: Klevno V. A. , Arefev M. L. 
Published: May 2019

Aim: to analyze the pool of potential donors in the Moscow region from among the corpses received for forensic medical examination, the effectiveness of their use, the assessment of the participation of the forensic service in transplantation coordination.Materials and methods. The potential donors from among the dead persons in 2017 from various injuries were analyzed, the conclusions of forensic experts in cases of the removal of internal organs from the corpse were studied.Results. In 2017, 417 forensic examinations of corpses with open and closed isolated traumatic brain injuries received as a result of various injuries were conducted. 328 corpses of males and 89 females, dominated by the age group of 61 and above – 170 (40.7%). The period of hospitalization 2–7 days – 173 (41.8%). In addition, 76 cases of no traumatic hemorrhages in the brain and under the matter of the brain caused by diseases were studied, the age was more than 60 years – 41 (53.9%) prevailed. In 29 cases, internal organs were taken for transplantation. Such corpses were investigated in 15 forensic departments out of 47 (31.9%), which are part of 8 departments of the Ministry of health of the Moscow region out of 15. Among donors, the prevalence of men 27 (93%) over women 2 (7%) in the 31–60 age group is 19 (65.5%). 17 were diagnosed with brain death (58.6%) and 12 asystolic donors (41.4%). Multiorgan removal was carried out in 13 cases (44.8%), in 15 cases kidneys were removal (51.7%), 1 case of refusal of the removal after visual inspection of the extracted organ.Conclusion. The Analysis allows to estimation a possible pool of potential donors in the Moscow region, to correlate with the volume of removal organs, which indicates insufficient efficiency of their use. Insufficiently active participation of medical institutions of Administrations of transplantological coordination in the territory of the Moscow region correlates with participation of medico legal experts in this coordination. In the conclusions of the experts found no evidence of traumatic damage to the organ and the obstruction of the expert when giving answers to the questions of the investigatory organizations.