Development of the method of receiving culture of cells of adenokartsinoma from the metastasis of the breast cancer. Development of model for carrying out laboratory researches for optimization of medical algorithm for maintaining patients

In work the algorithm of receiving culture of cages of a metastasis of a breast cancer for its use as model for carrying out the clinical and safe laboratory researches directed on optimization of medical algorithm for maintaining patients with metastatic damage of a spine column is presented. The received results testify that klonogenny and proliferative activity, and also morphology of the cellular lines allocated from different clones of one tumor differs that allows to assume various induced immunogenicity. The developed algorithm can be used for receiving cellular cultures from tumoral fabrics for creation of an antineoplastic vaccine, researches of an additional expression of genes on the transformed cages, increase of efficiency of the personified therapy for patients of an oncologi profile.В работе представлен алгоритм получения культуры клеток метастаза рака молочной железы для использования ее в качестве модели для проведения клинически-безопасных лабораторных исследований, направленных на оптимизацию лечебного алгоритма для ведения пациентов с метастатическим поражением позвоночного столба. Полученные результаты свидетельствуют, что клоногенная и пролиферативная активность, а также морфология клеточных линий, выделенных из разных клонов одной опухоли отличается, что позволяет предположить различную индуцируемую иммуногенность. Разработанный алгоритм может быть использован для получения клеточных культур из опухолевых тканей для создания противоопухолевой вакцины, исследований добавочной экспрессии генов на трансформированные клетки, повышения эффективности персонифицированной терапии для пациентов онкологического профиля

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Renal replacement therapy after liver transplantation

Objective: to analyze the causes of acute renal failure (ARF) and to study the efficiency of renal replacement therapy (RRT) in the treatment of this condition after liver transplantation.Materials and methods. Eighty liver transplantations made at the N.V. Sklifosovsky Research Institute of Emergency Care from 2000 to 2008 were analyzed. The patients were divided into 2 groups: 1) 29 patients with evolving ARF who received RRT in the postoperative period; 2) 51 patients who had no indications for RRT.Results. Postoperative RRT was performed in 29 (36.3%) patients. Of them, 23 patients had been identified to have the hepatorenal syndrome in the preoperative period. Renal function recovered in 20 (72.4%) of the 29 patients who needed RRT during the performed treatment and they were discharged from the clinic. Due to the conducted treatment, these patients showed stabilization and their ARF resolution occurred within 12.7±6.2 days. The mean number of performed sessions required to restore renal function was 8.8 (range 1 to 56).Conclusion. Preoperative hepatorenal syndrome is a predictor of ARF in the postoperative period. At the same time ARD has a good prognosis after liver transplantation. With a primary non-functioning graft, extracorporeal techniques are ineffective and maintenance therapy used prior to liver retransplantation

Effect of selenium on the course of a postoperative period after liver transplantation

Objective: to study the effect of selenium on the course of a postoperative period in patients after orthotopic liver transplantation (OLT).Subjects and methods. The prospective controlled randomized study enrolled 30 patients after OLT. Selenium (Selenase, Biosyn) was administered in Group 1 (n = 15) within 5 days operatively. The agent was not used in complex therapy in Group 2 (n = 15).Results. After OLT, the plasma levels of selenium were much more than the normal value. In Group 1, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly lower on day 3 after OLT and those of urea and creatinine significantly decreased by day 7. A significant difference was found in scores on day 7, as shown by the analysis of the patients' condition by the SOFA scale. The patients who needed venovenous hemodiafiltration (VVHDF) were more than in those who did not use selenium.Conclusion. Selenium levels considerably decrease after liver transplantation. Selenase has a hepatoprotective effect, alleviates the manifestations of a systemic inflammatory response, and reduces the frequency of VVHDF use

Fish introductions in the former Soviet Union: The Sevan trout (Salmo ischchan) - 80 years later.

The Soviet Union played the leading role in fish introductions in Eurasia. However, only 3% of all introductions prior to 1978 gave a commercial benefit. One of the noteworthy examples appears to be the Sevan trout (Salmo ischchan Kessler, 1877)-an endemic salmonid of Lake Sevan in Armenia. This species has been introduced to Kirghizstan, Kazakhstan, and Uzbekistan, however, only the Kirghiz population has persisted in relatively high numbers. In this paper we provide the first extensive molecular study of S. ischchan using samples from the native population from Lake Sevan and three hatcheries in Armenia, as well as from the population introduced to Lake Issyk Kul in Kirghizstan. The Kirghiz population has been isolated since the introductions took place in 1930 and 1936. Our results, based on 11 nuclear microsatellites and a 905 bp fragment of the mitochondrial control region suggest that hatcheries have maintained genetic variability by way of ongoing translocations of individuals from Lake Sevan. Simultaneously, significant Garza-Williamson M-values suggest that bottlenecks could have reduced the genetic variability of the wild populations in the past. This hypothesis is supported by historical data, indicating highly manipulated water-level regulations and poaching as two main factors that dramatically impact fish abundance in the lake. On the other hand, a similar situation has been observed in Kirghizstan, but this population likely rebounded from small population size faster than the other populations examined. The Kirghiz population is significantly genetically differentiated from the other groups and have morphological features and biological attributes not observed in the source population. Genetic data imply that the effective population size in the native population is lower than that found in the introduced population, suggesting that some active protection of the Lake Sevan population may be needed urgently