[Identification of Melittin-Like Proteins with a Molecular Weight of 67 κDa that Interact with Na

Melittin, a peptide from bee venom, was found to be able to interact with many proteins, including calmodulin target proteins and ion-transporting P-type ATPases. It is assumed that melittin mimics a protein module involved in protein-protein interactions within cells. Previously, a Na^(+)/K^(+)-ATPase containing the α1 isoform of the catalytic subunit was found to co-precipitate with a protein with a molecular weight of about 70 κDa that interacts with antibodies against melittin by cross immunoprecipitation. In the presence of a specific Na^(+)/K^(+)-ATPase inhibitor (ouabain), the amount of protein with a molecular weight of 70 κDa interacting with Na^(+)/K^(+)-ATPase increases. In order to identify melittin-like protein from murine kidney homogenate, a fraction of melittin-like proteins with a molecular weight of approximately 70 κDa was obtained using affinity chromatography with immobilized antibodies specific to melittin. By mass spectrometry analysis, the obtained protein fraction was found to contain three molecular chaperones of Hsp70 superfamily: mitochondrial mtHsp70 (mortalin), Hsp73, Grp78 (BiP) of endoplasmic reticulum. These data suggest that chaperones from the HSP-70 superfamily contain a melittin-like module.

The Role of NMDA Receptor Subunits in the Effect of Memantine on the Brain of Healthy Animals.

The non-competitive NMDA glutamate receptor antagonist memantine has neuroprotective properties and is the first non-cholinergic drug approved for the treatment of Alzheimer's disease. The purpose of this work was to test the hypothesis that injections of memantine to healthy animals can affect the subunit composition of NMDA receptors in the brain, which may explain the effects of its chronic administration. For this, the expression of subunits GluN1, GluN2A, GluN2B, and GluN2C was studied in the hippocampus and prefrontal cortex of rats after single or five subchronic injections of memantine. The results showed that the GluN2C subunit (GRIN2C) plays an important role in the effects of memantine; against the background of memantine treatment, the expression of this subunit markedly decreased in the prefrontal cortex, but not in the hippocampus, which significantly affected the excitation/inhibition balance in cortical structures.

[Experience in performing robot-assisted radical prostatectomy in patients after heart transplan- tation].

INTRODUCTION: Prostate cancer (PCa) occupies a leading position in the structure of oncological morbidity and mortality and is an urgent problem of modern oncourology. In recipients after organ transplantation, due to the intake of immunosuppressants, the risk of aggressive forms of cancer increases, which necessitates active treatment. In the world, there is not enough data on the radical treatment of PCa in patients after heart transplantation (HT), especially on surgical treatment. We present the first experience in Russia and Eastern Europe of 3 robot-assisted radical prostatectomy for localized PCa in patients after HT. MATERIALS AND METHODS: The procedures were performed from February 2021 to November 2021 at the FGBU NMRC named after V.A. Almazov. Preoperative preparation, as well as postoperative management of patients was carried out jointly by urologists and transplant cardiologists. RESULTS: The main demographic, perioperative indicators, as well as oncological and non-oncological outcomes are presented. All patients were discharged from the hospital in a satisfactory condition. During the follow-up period, there were no biochemical recurrences of PCa. Early urinary continence in all three patients was satisfactory. CONCLUSION: Thus, robot-assisted radical prostatectomy in patients after HT is a technically feasible, effective, and safe treatment for PCa. The comparative studies with prolonged follow-up are needed.

Ouabain and Marinobufagenin: Physiological Effects on Human Epithelial and Endothelial Cells.

Long-term study on the identification of Na,K-ATPase endogenous inhibitors in mammalian tissues has resulted in the discovery of ouabain, marinobufagenin (MBG), and other cardiotonic steroids (CTS) in the blood plasma. Production of ouabain and MBG is increased in essential hypertension and other diseases associated with hypervolemia. Here, we compared the effects of ouabain and MBG on the Na,K-ATPase activity (measured as the transport of Na+, K+, and Rb+ ions) and proliferation and death of human renal epithelial cells (HRECs) and human umbilical vein endothelial cells (HUVEC) expressing α1-Na,K-ATPase. Ouabain concentration that provided the half-maximal inhibition of the Rb+ influx (IC50) into HRECs and HUVECs was 0.07 µM. In both types of cells, the IC50 values for MBG were 10 times higher than for ouabain. Incubation of HREC and HUVEC with 0.001-0.01 µM ouabain for 30 h resulted in 40% increase in the [3H]thymidine incorporation into DNA; further elevation of ouabain concentration to 0.1 µM completely suppressed DNA synthesis. MBG at the concentration of 0.1 µM activated DNA synthesis by 25% in HRECs, but not in HUVECs; 1 µM MBG completely inhibited DNA synthesis in HRECs and by 50% in HUVECs. In contrast to HRECs, incubation of HUVECs in the serum-free medium induced apoptosis, which was almost completely suppressed by ouabain and MBG at the concentrations of 0.1 and 3 µM, respectively. Based on these data, we can conclude that (i) the effect of MBG at the concentrations detected in the blood plasma (<0.01 µM) on HRECs and HUVECs was not due to the changes in the [Na+]i/[K+]i ratio; (ii) the effect of physiological concentrations of ouabain on these cells might be mediated by the activation of Na,K-ATPase, leading to cell proliferation.

Effects of Dynamic and Static Loads on the Concentration of Sodium and Potassium in Murine Skeletal Muscles.

The effects of dynamic and static load on the intracellular concentrations of sodium [Formula: see text] and potassium (K+i) in m. soleus and m. biceps, respectively, were studied in mice. Both dynamic (swimming for 60 min) and static (hanging on the grid for 40 min) load led to a 2-fold increase in [Formula: see text] level, a decrease in K+i concentration by 25-35%, and 3-4-fold increase in the [Formula: see text] ratio. These effects of dynamic and static loads on the studied parameters remained unchanged in mice subjected to regular physical exercise (swimming or hanging on the grid for 1 h a day over 4 weeks). Our results suggest that dissipation of sodium and potassium transmembrane gradients during physical exercise can be considered as a factor of regulation of functional activity of skeletal muscles, which includes changes in transcription and translation of myokines observed previously.

[ROENTGEN-ENDOVASCULAR EMBOLIZATION OF THE PORTAL VEIN BRANCHES AS A PATIENTS CONDITIONING FOR EXTENSIVE HEPATIC RESECTION].

The results of surgical treatment of 316 patients, suffering focal hepatic diseases, in whom for preoperative preparation a portal vein embolization (PVE) was performed, were analyzed. PVE was applied in a small planned hepatic residual volume. The patients have aged from 21 to 77 yrs, (57 ± 10.6) yrs at average. During (22 ± 7) days after the procedure a hypertrophy of a planned postresectional hepatic volume by 58.6% was observed, while a hypertrophy degree have depended on the embolization volume performed: 57.3%--after embolization of branches of C(V)-C(VIII) hepatic segments, 66%--the segments C(V)-C(VIII) + C(IV). In 281 (89%) patients the extensive hepatic resection was performed, a fatal postresection hepatic insufficiency was not observed. A three-year and five-year disease-free survival have constituted 43.8 and 16.4% accordingly. Thus, a PVE constitutes a miniinvasive intervention, permitting to achieve a planned residual hepatic volume, to expand a diapazon of application of radical extensive hepatic resection in patients, suffering focal hepatic diseases while a small planned residual hepatic volume.

[Preoperative portal vein embolization: dynamics of portal pressure].

The pressure dynamics was studied in a portal vein (PV) in patients, suffering focal hepatic pathology, to whom portal vein embolization (PVE) was performed as a stage of preparation to radical hepatic resection. In 236 patients the immediate measurement of pressure in a PV was performed intraoperatively before and after PVE, in 26 - catheter for control portography and monitoring of pressure in a PV was left in its trunk for 24 h postoperatively. There was noted a pressure rising in a PV immediately after its embolization by 86.7%, positive correlation was established between PVE volume and pressure gradient in a PV before and after it. While doing monitoring during 24 h there was observed the pressure rising in a PV during 3 h after its embolization with subsequent lowering down to initial. Application of PVE as a preparation procedure for performance of extended hepatic resection, together with enhancement of residual liver minimizes sharp postresectional pressure rising in PV, what constitutes essential factor of the hepatocytes damage of residual hepatic part in immediate postoperative period.

[Results of preoperative embolization of portal vein in patients with biliary hepatic tumors].

The results of preoperative embolization of portal vein (EPV) in 90 patients, operated on for biliary hepatic tumors, were analyzed. In 47 patients Klatskin tumor was revealed, in 29--peripheral cholangiocarcinoma, in 14--tumor of a gallbladder. In all the patients a radical major hepatic resection was planned, a checking hepatic volume (CHHV) did not exceed 40% of a noninvolved parenchyma. The EPV volume have corresponded generally to the planned resection volume. After performance of EPV a pressure in a portal vein have risen by 75%, and later it have had lowered step by step during 24 h. The CHHV index have raised from (354 +/- 72) up to (462 +/- 118) cm3, or from (33 +/- 7) up to (45 +/- 11)%, permitting to perform radical hepatic resection in 79 (87.8%) patients. Thus, application of EPV in patients, suffering biliary hepatic tumors, have permitted to increase the CHHV index after radical resection, and to raise resectability of such tumors.

Relative isomer abundance of fullerenes and carbon nanotubes correlates with kinetic stability.

A methodology to evaluate the kinetic stability of carbon nanostructures is presented based on the assumption of the independent and random nature of thermal vibrations. The kinetic stability is directly correlated to the cleavage probability for the weakest bond of a given nanostructure. The application of the presented method to fullerenes and carbon nanotubes yields clear correlation to their experimentally observed relative isomer abundances. The general and simple formulation of the method ensures its applicability to other nanostructures for which formation is controlled by kinetic factors.

[A portal vein branch embolization as a method of preparation for liver resection].

The results of preoperative transcutaneous transhepatic embolization of portal vein (PTTEPV) were analyzed in 86 patients, suffering malignant hepatic tumors. Depending on a planned hepatic resection (HR) volume there was conducted embolization of a right lobar portal vein (in 45 patients), right vein with a vein of C(IV) segment (in 32), lobar portal vein with anterior right vein (in 9). In 3-4 weeks after PTTEPV there was noted the enhancement of ratio of a planned residual hepatic volume/total hepatic volume from 16.3 to 27.5%, permitting to perform HR successfully in these patients. In 4 (4.7%) patients HR was not performed because of progressing of the tumor development or a total thrombosis of portal vein. The data obtained witness, that PTTEPV constitute an effective method of the patients preparation for HR while presence of a planned small residual hepatic volume.

[The portal vein reconstruction during operations for hepatocellular carcinoma].

There was the objective to improve the results of treatment in patients, suffering hepatocellular carcinoma (HCC) with vena cava invasion by the tumor. In the main group a hepatic resection with the portal vein resection and portoplasty was performed in 21 patients, suffering HCC with vena cava invasion by the tumor of second-third degree (according to J. Shi, 2007); in a control group in 61 patients, suffering the portal vein tumoral invasion of first degree, the hepatic resection only was done. The mortality have constituted 9.5% in the main group and 8.1%--in a control one. The 5-year survival index have constituted 11.5%--in the main group and 25.3%--in a control one. The aggressive surgical tactics application for HCC with portal vein tumoral invasion permits to enhance the indices of the patients far-remote survival.

Na+ i/K+ i imbalance contributes to gene expression in endothelial cells exposed to elevated NaCl.

High-salt consumption contributes to the development of hypertension and is considered an independent risk factor for vascular remodelling, cardiac hypertrophy and stroke incidence. Alterations in NO production, inflammation and endothelial cell stiffening are considered now as plausible mediators of cardiovascular dysfunction. We studied early responses of endothelial cells (HUVEC) caused by a moderate increase in extracellular sodium concentration. Exposure of HUVEC to elevated sodium within the physiological range up to 24 h is accompanied by changes in monovalent cations fluxes and Na,K-ATPase activation, and, in turn, results in a significant decrease in the content of PTGS2, IL6 and IL1LR1 mRNAs. The expression of NOS3 and FOS genes, as well as the abundance of cytosolic and nuclear NFAT5 protein, remained unchanged. We assessed the mechanical properties of endothelial cells by estimating Young's modulus and equivalent elastic constant using atomic force and interference microscopy, respectively. These parameters were unaffected by elevated-salt exposure for 24 h. The data obtained suggest that even small and short-term elevations of extracellular sodium concentration affect the expression of genes involved in the control of endothelial function through the Na+ i/K+ i-dependent mechanism(s).

[Antibacterial therapy in surgical treatment of chronic hepatic abscess].

The results of surgical treatment of 58 patients for chronic hepatic abscess were presented. In patients of the main group hepatic resection was performed and in a control one--sanation and drainage of the abscess cavity. Antibacterial therapy was conducted in patients of both groups before and after operative treatment. The peculiarities and common efficacy of antibacterial therapy depending on the operative treatment kind were noted.

[Peculiarities of the venous bed vessels reconstruction while performing liver transplantation from live relative donor in children].

The rate of hepatic transplantation from live relative donor in children is increasing in all over the world and in Ukraine as well. Significant incidence of the pathology together with necessity of technically complex intervention performance causes the need for surgical technique improvement, a new methods elaboration and clinical introduction, permitting to lower the postoperative complications rate. Technical complexity constitutes the main peculiarity of transplantation operation of liver, obtained from live relative donor, in children, it is caused by the vessels small diameter, pathological changes of the recipient portal vein and lack of plastic material for reconstruction of vessels. There are proposed various plastic methods for the transplant portal inflow and venous outflow guaranteeing to achieve a success while performing left lateral hepatic section transplantation, permitting to improve the results of hepatic transplantation from live relative donor in children.

[Hepatic and the portal vein resection in the surgical treatment of hepatocellular carcinoma].

Modern problems of the portal vein resection while hepatectomy performance are enlighted. Indications for resection of the portal vein bifurcation zone are adduced, various methods of portoplasty are depicted. New methods of the portal vein passability restoration in disparity of its sutured parts diameters are proposed. The results of hepatectomy combined with portal vein resection are studied.