[The efficiency of pre-administration of a peptide mimicking the spatial structure of erythropoietin -chain B in modeling experimental post-contrast acute kidney injury].

AIM: To study the efficiency of pre-administration of a peptide mimicking the spatial structure of erythropoietin -chain B in modeling experimental post-contrast acute kidney injury. MATERIALS AND METHODS: In this study, an experimental model of post-contrast acute kidney injury was created using a non-steroidal anti-inflammatory drug, a nitric oxide synthase inhibitor, and injection of iopromide to mature male mice. After 48 hours, a comprehensive assessment of the concentration of creatinine, urea, glomerular filtration rate, the ratio of urea/albumin in the serum, as well as the level of proteinuria and interleukin 6 in the urine was carried out. RESULTS: A peptide mimicking the spatial structure of erythropoietin -chain B, administered at a dose of 100 g/kg 30 minutes before modeling of pathologic process, contributes to a significant decrease in creatinine and urea concentrations by 2.5 and 1.8 times, respectively, with an increase in glomerular filtration rate 4.4 times. In addition, in the group with pharmacological correction, there was a significant decrease in the ratio of urea/albumin by 2.2 times, a decrease in the level of proteinuria by 61.9% and a decrease in the concentration of pro-inflammatory interleukin-6 in the urine by 2.1 times. CONCLUSION: Thus, the preliminary administration of a peptide that mimics the spatial structure of the erythropoietin -chain B helps to reduce the severity of post-contrast acute kidney injury in the experiment, due to anti-inflammatory properties.

[Synergism of carbamylated darbepoetin and L-ethoxidol in the model of experimental kidney ischemia].

AIM: to determine the efficiency of different doses of erythropoietin and carbamylated darbepoetin, to prove experimentally the possibility of increasing the efficiency of carbamylated darbepoetin when using the levorotatory stereoisomer of ethoxidol. MATERIALS AND METHODS: On the model of ischemia-reperfusion injury in male CD-1 mice that were undergone to contralateral nephrectomy, the nephroprotective effect of different doses of erythropoietin alfa, carbamylated darbepoetin, L-ethoxidol (the levorotatory enantiomer of ethylmethylhydroxypyridine malate), and the combined use of L-ethapylated carboxypyridine malate and L-etapoietin alfa was studied. The parameters of microcirculation and glomerular filtration rate were studied one day after 30-minute ischemia. RESULTS: It has been established that the prophylactic use of erythropoietin alfa and carbamylated darbepoetin in the model of ischemia-reperfusion injury of a single kidney reduces the severity of microcirculatory impairment and ensures the preservation of the glomerular filtration rate in dose-dependent manner. The synergistic effect of L-ethoxidol and carbamylated darbepoetin was found when these substances were used together. CONCLUSION: Prevention of ischemia-reperfusion kidney injury by analogs of human erythropoietin and their combination with ethylmethylhydroxypyridine derivatives is experimentally-proved.

[The significance of detection of nitrites in oral fluid of healthy people.]

The nitric oxide is a signal molecule in human organism characterized by a wide spectrum of biological effects. The exogenous nitric oxide is formed from food nitrates received with such green leafy vegetables as spinach, parsley, sorrel and also beet, cucumbers and tomatoes. The bacteria in oral cavity metabolize received with food nitrates up to nitrites. The nitrites as some intermediate metabolites of nitric oxide sufficiently exact reflect concentration of nitric oxide. The purpose of study is to examine analytical dependence and efficiency of express-device for detecting nitrites in saliva. The article presents the results of confirmation of testsystem for half-quantitative detection of content of nitrites in saliva. The device represents a hollow tube with a sensorial element within functioning by the principle of "dry chemistry". The concentration of nitrites in oral cavity was measured in 100 healthy people of both genders aged from 16 to 45 years. In case of consuming vegetables every day or 3-5 times a week higher levels of nitrite-anions (14,9-15,7 mg/l) are registered than in case of consuming vegetables and juices 1-2 times a week and rarely (9,9 mg/l). The concentrations of nitrites in saliva both in cases of regular training and low-activity life-style are within the limits of standards (11,9-14,9 mg/l). The average level of nitrites in saliva of participants of experiment with normal pressure made up to 16.5 mg/l that is significantly higher than in individuals from groups with increased and decreased arterial pressure (10,2 and 10,4 mg/l correspondingly).

[The role of pharmacological preconditioning in renal ischemic and reperfusion injury].

Renal ischemic and reperfusion injury resulting in acute renal failure is a multidisciplinary problem at the junction of pathophysiology, transplantology, urology, nephrology, cardiac surgery and pharmacology. One of renal protection strategies is using the phenomenon of preconditioning. Preconditioning is one of the ways to adopt a tissue to repeated short-term effects of damaging factors to induce an enhanced tolerance to the long period of hypoxia and/or ischemia. There are multiple cellular and molecular mechanisms of the renal protective effects of preconditioning stimuli, but the key effectors and signaling molecules are ATP-dependent potassium channels, nitric oxide synthase, nitric oxide, and mitochondrial pore. Contradictory data on the protective effect of ischemic preconditioning allow searching for approaches to pharmacological correction of ischemic and reperfusion injuries. The article provides data on possible ways of using erythropoietin, darbepoetin and phosphodiesterase 5 inhibitors.

[The development of express-test for semiquantitative detection of thiocyanate ions in saliva.]

The article presents the results of approbation of the express test-system for semi-quantitative detection of content of thiocyanate ions in saliva as markers of tobacco smoking. The device corresponds to hollow tube with sensory element inside functioning on the principle of "dry chemistry". At saliva intake, the analyzing component (thiocyanate ion) interacts with reagents of sensory element with formation of colored thiocyanate complex. The intensity of color of formed complex permits to judge about content of thiocyanates in saliva by comparison with standard scale. The concentration of of thiocyanate ions in oral fluid of 100 health people of both genders aged from 16 to 45 years was analyzed. The questionnaire survey of respondents was carried out to establish smoking and non-smoking contingents. The analysis established that 30% were active tobacco smokers. The everyday smokers made up to 50% out of them, non-regular smokers (several cigarettes per week or month) - 50%. The reliable relationship between intensity of smoking and concentration of thiocyanate ions in saliva is established. The level of thiocyanate ions in saliva is significantly higher (2.5 mmol/l) in the group of everyday smokers than in saliva of non-smokers of periodically using tobacco articles (0.3-0.5 mmol/l) The increased concentrations of thiocyanate ions in saliva (≥ 1,5 mmol/l) were established in 7% of nonsmokers and are possible related to consumtion of food containing glucosinolates. The test is efficient for detecting smokers using from 1 to 10 cigarettes per day. However, it is of no use in case of sporadic type of smoking.

[THE EFFECT OF PLAKOPHILIN-2 GENE MUTATIONS ON ACTIVITY OF THE CANONICAL Wnt SIGNALING PATHWAY].

Plakophilin-2 is a desmosomal protein encoded by PKP2 gene. Desmosomal proteins are usually considered as structural proteins with the main function of maintaining intercellular interactions. Genetic studies revealed that mutations in desmosomal genes could lead to arrhythmogenic right ventricular cardiomyopathy, heart disease characterized by substitution of cardiomyocytes by adipose and fibrotic tissue predominantly in right ventricle. Wnt signaling pathway is one of the signal transduction pathways which could be involved in the formation of the pathology. The purpose of this study was to investigate Wnt activity changes caused by PKP2 mutations during adipogenic and cardiomyogenic differentiation. We used multipotent mesenchymal stromal cells and iPS cells generated from patient carrying PKP2 gene mutation. We show that Wnt activity is lower in the cells with mutant PKP2. This data indicate a possible signaling role of plakophilin-2 by regulating Wnt activity.

[Functional properties of smooth muscle cells in ascending aortic aneurysm].

Thoracic aortic aneurism (TAA) develops as a result of complex series of events that dynamically alter the structure and composition of the aortic vascular extracellular matrix (ECM). The main elements that alter the composition of aortic wall are smooth muscle cells (SMC). The purpose of the present work was to study alteration of smooth muscle cell functions derived from the patients with TAA and from healthy donors. As it is supposed that TAA associated with bicuspid aortic valve (BAV) and with tricuspid aortic valve (TAV) differ in their pathogenesis, we compared the SMC and tissues samples from BAV-, TAV-patients and healthy donors. We compared TAA patients' derived tissues and SMC to healthy donors' ones in several parameters: SMC growth, migration and apoptotic dynamics; metalloproteinase MMP2 and MMP9 activity (zymography) and elastin, collagen and fibrillin content (Western blot) in both tissue samples and cultured SMC. Proliferation ability of both BAV and TAV SMC was decreased comparing to donors cells; migration ability in scratch tests was increased in TAV-derived SMC comparing to donor cells. BAV-cells migration ability was not changed comparing to donor-SMC. Elastin content was decreased in TAA SMC comparing to donor cells whereas the content of fibrillin and collagen was not altered. At the same time elastin and collagen protein level was significantly higher in tissue samples of TAA patients comparing to donor-derived samples. SMS proliferation and migration ability is differently affected in TAV and BAV-associated TAA that supports the idea of different nature of these two groups of TAA. Also our data show that SMC functional properties are altered in TAA patients and these alterations could play a significant role in the disease pathogenesis.