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Objective: To compare structural changes in tissues with clinical and laboratory parameters and immunohistochemical determination of proteins HIF1α, HIF2α, caspase-3 during cellular alteration under conditions of hypoxia in the liver and kidneys in an experiment on pigs., Material and Methods: Laboratory parameters related to the state of gas exchange (decrease in partial pressure of arterial blood oxygen (PaO2), arterial blood saturation, lactate level, kidney function (creatinine, urea) and liver (ALT, AST, bilirubin) in 18 animals were analyzed in comparison with the results of a morphological study. Histological examination evaluated alterative and inflammatory tissue changes of varying severity, and also determined the expression of transcription factors HIF1α and HIF2α and a marker of apoptosis - caspase-3. The ratio between laboratory parameters and structural changes was assessed individually for each animal., Results: In the liver, a statistically significant dependence of the content of HIF2α protein in cells on the severity of dystrophic changes and serum lactate levels was revealed. A statistically significant correlation was shown between an increase in transaminase and bilirubin levels and the severity of alterative changes in liver tissue. However, there was no significant relationship between the number of caspase-3 positive cells and the severity of dystrophic changes. A statistically significant correlation was found between creatinine and urea levels and the severity of alterative changes in kidney tissues. With significant dystrophic changes, a statistically significant dependence of the expression of HIF2α and caspase-3 proteins and a very high correlation of caspase-3 - lactate indicators were revealed., Conclusion: A significant correlation was shown between histological changes in tissues and clinical and laboratory parameters. Severe hypoxia with lactate accumulation directly affects the integrity and function of cells, which manifests itself in structural changes. Based on the results of a comparative study, it can be concluded that the assessment of alterative changes in liver and kidney tissues is important.

The aim of our study was to assess morphological changes in internal organs in a redox-induced model of alloxan diabetes in rats.According to the results of the study, the blood glucose level in rats began to increase 24 hours after the of alloxan administration, reached the maximum level on the 15th day of observation, and decreased on the 25-35 day, to the control level. In parallel with the increase in blood glucose level, an increase in the malondialdehyde (MDA) content in the blood serum was observed.Severe hyperemia, edema, and focal fibrotic changes were revealed morphologically in the kidneys, liver and myocardium. The degree of morphological changes was increased (lymphocytic-cell infiltration, degenerative changes (dystrophy), small necrotic areas) with an increase in the level of glucose and MDA in the blood. It can be assumed that the damage to the tissues of the kidneys, heart, liver and blood vessels in diabetes is largely due to the intensification of oxidative stress in the body.

Modern view on pathogenesis of immunoglobulin (Ig)A-nephropathy and possible relation to intestinal MALT-system activity is presented in the article. Aberrant glycosylation of IgA and increased association of IgA-nephropathy with intestinal diseases or abnormal intestinal permeability are discussed in details. Based on supposed entero-renal pathogenesis of the disease future treatment modalities are considered. Relevant worlds literature is cited.

Objective - to find out the possibility of using molecular hydrogen in the correction of no-reflow syndrome in the polyuric stage of acute kidney injury 72 hours after the administration of mercuric chloride in rats on a hyposodium diet. The experiments were performed on 60 male white non-linear sexually mature rats weighing 0.16-0.18 kg to study the effect of water loading with saturation with molecular hydrogen. Sublimate nephropathy was modeled under conditions of a hyposodium diet by subcutaneous injection of 0.1% mercury dichloride solution at a dosage of 5 mg/kg with a study after 72 hours, which corresponded to the early polyuric stage of acute kidney injury and the development of no-reflow syndrome. To saturate the water with molecular hydrogen at a concentration of 1.2 ppm and a redox potential from -100 to -350 mV, a new generation H2 generator Blue Water 900 (Korea) was used, containing an improved proton-exchange membrane PEM/SPE. Used: pathophysiological, biochemical, functional, chemiluminescent, statistical research methods. The antioxidant effect of loading with water with saturation with molecular hydrogen leads to a decrease in the loss of sodium ions due to an improvement in its reabsorption and β2-microglobulin in the proximal tubule, a decrease in lipid peroxidation in the renal cortex was noted, the degree of its damage by an increase in the K+/Na+ ratio and a decrease in degree of edema. Improvement in the condition of the proximal nephron led to an increase in total, enzymatic fibrinolytic activity in the renal cortex. The increase in the activity of succinate dehydrogenase in the renal cortex is due to an increase in the delivery of electrons due to the negative redox potential and the selective antioxidant effect of molecular hydrogen. The anti-edema effect of molecular hydrogen was revealed at the level of 7 layers of the kidney. During the formation of the no-reflow syndrome in rats on a low-sodium diet 72 hours after the introduction of mercuric chloride, the possibility of breaking large and small vicious circles with an antioxidant solution of H2 was shown due to its high permeability and the ability to neutralize the hydroxyl radical and peroxynitrite.

The maintenance of energy homeostasis of the body according to modern data is carried out with the active participation of dopaminergic neurons of the central nervous system. The synthesis and metabolism of dopamine (DA) occurs both in the brain and in peripheral tissues. Violation of the synthesis and metabolism of DA is considered as a link in the vicious cycle which it formed during the development of diet-induced obesity. According to modern data, a number of essential and toxic trace elements, such as Cd, Al, As, Mn, Fe, Cu, Zn, are actively involved in the exchange of DA in the brain and peripheral organs and tissues. One way to assess this relationship is to compare changes in the microelement status of the organism when consuming hypercaloric diets in animals with normal and impaired DA transport. The latter can be animals with a knockout of the DAT transporter gene, which performs DA reabsorption with subsequent storage in the composition of secretory granules. The aim is a comparative study of the content of a number of essential and toxic elements in the brain, liver, and kidneys of rats that differ in the allelic variants of the DAT gene fed balanced diet and the diet with an excess of energy value. Material and methods . The study was carried out on 30 male rats of the DAT-KO knockout line (homozygotes DAT-/- and heterozygotes DAT+/-), 8-10 weeks old, and 13 males rats of the outbred Wistar line (DAT+/+) of the same age. For 62 days the animals (6 groups) received a semi-synthetic diet containing essential elements in the salt mixture or a similar high-fat-highcarbohydrate diet (HFCD) with 30% fat and 20% fructose solution instead of drinking water. The content of 16 trace elements (Fe, Mg, Cu, Mn, Co, Se, Zn, Cr, V, Cs, Ag, Al, Cd, As, Pb, Ni) were determined by inductively coupled plasma mass spectrometry in the liver, kidneys, and brain of rats with a knockout of the dopamine DAT transporter gene: homozygotes (DAT -/-) and heterozygotes (DAT+/-), as well as wild-type rats (DAT+/+) of the Wistar strain. Results and discussion . In the liver, DAT knockout led to an increase in the content of As, Cd, Co, and Cs and a decrease in Fe; in the kidneys - to an increase in the levels of Pb, As, Cd and Se, in the brain - an increase in the content of most of the studied trace elements, including Pb, As, Cs, Al and Cu. Conclusion . Against the background of consumption of HFCD, the effect of DAT knockout on the content of a number of elements was more pronounced compared with the consumption of the control diet. The revealed changes in the trace element content in DAT knockout rats are considered in terms of the effect of DA metabolism in the central nervous system and in peripheral tissues on the status of trace elements., Competing Interests: The authors declare no overt and potential conflict of interest related to the publication of this article., (Copyright© GEOTAR-Media Publishing Group.)

Aging causes significant changes in the kidneys. One of the most important manifestations of an aging kidney is a reduction in glomerular filtration rate (GFR). Unfortunately, there is no generally accepted, adequate method for evaluating GFR in the elderly. The perspectivies of the relatively new approaches (BIS1, BIS2, FAS) are not clear and doubtful. The feasibility of standardization of GFR values by body surface area among of the older persons has not been determined. Possible that the diagnosis setting «chronic kidney disease» in elderly solely on the base of GFR decline may be an inadequate approach and promote a kind of «nephrological ageism».

A comparison of the lipofuscin (aging pigment) content in four organs (liver, kidney, heart, brain) of young and adult rats, as well as in a suspension of hepatic mitochondria, was made. It was demonstrated that mitochondrial lipofuscin - mitolipofuscin, fluorescing in the blue region, makes the main contribution to hepatic lipofuscin. It is assumed that mitolipofuscin in other organs also makes a significant contribution. It is shown that accumulation of lipofuscin with age occurs in all organs of rats, but least of all in the brain. In addition to fluorescent lipofuscin, non-fluorescent protein aggregates are found in all organs, the largest number of which is found in the heart. Among them, a significant proportion is covalently cross-linked aggregates that are not destroyed by detergents. Their number also increases with age.

Aim: To investigate experimentally ultrastructural and biochemical signs of acute injury to the renal parenchyma after warm renal ischemia of various duration and subsequent reperfusion., Materials and Methods: The experiments were performed on 44 healthy conventional female rabbits of the "Chinchilla" breed weighted 2.6-2.7 kg, which were divided into four groups. In the first, control, group included pseudo-operated animals. In the remaining three groups, an experimental model of warm ischemia of renal tissue was created, followed by a 60-minute reperfusion. The renal warm ischemia time was 30, 60 and 90 minutes in the 2nd, 3rd and 4th groups, respectively. Electron microscopy was used to study ultrastructural disturbances of the renal parenchyma. Biochemical signs of acute kidney damage were detected by measuring the following blood serum and/or urine analytes: NGAL, cystatin C, KIM-1, L-FABP, interleukin-18. The glomerular filtration was evaluated by creatinine clearance, which was determined on days 1, 5, 7, 14, 21 and 35 of follow-up., Results: A 30-minute renal warm ischemia followed by a 60-minute reperfusion induced swelling and edema of the brush membrane, vacuolation of the cytoplasm of the endothelial cells of the proximal tubules, and microvilli restructuring. The observed disorders were reversible, and the epithelial cells retained their viability. After 60 minutes of ischemia and 60 minutes of reperfusion, the observed changes in the ultrastructure of the epithelial cells were much more pronounced, some of the epithelial cells were in a state of apoptosis. 90 min of ischemia and 60 min of reperfusion resulted in electron-microscopic signs of the mass cellular death of the tubular epithelium. Concentration in serum and/or biochemical urine markers of acute renal damage increased sharply after ischemic-reperfusion injury. Restoration of indicators was observed only in cases when the renal warm ischemia time did not exceed 60 minutes. The decrease in creatinine clearance occurred in the first 24 hours after the intervention, lasting not less than two weeks after a 30-minute warm ischemia, at least 3 weeks after a 60-minute warm ischemia and continued more than a month after a 90-minute renal artery occlusion., Conclusion: Intraoperative warm ischemia and subsequent reperfusion are the actual reasons for the alteration of the ultrastructure of the renal tissue and the impairment of the filtration function. The severity of the disorders depends on the duration of the damaging factors. After a 30-60-minute ischemia, the structural and functional changes in the renal tissue are reversible. The mass death of nephrocytes-effectors is possible only after warm renal ischemia longer than 60 min.

Warm ischemia of the renal parenchyma is a forced feature of laparoscopic partial nephrectomy. It is accompanied by oxygen deprivation of the organ and followed by re-oxygenation, which can cause additional damage to the renal tissue. This damage can result in acute functional and structural disorders of individual parts of the nephron, increasing the risk for a renal dysfunction. Timely diagnosis of the dysfunction is vital for the success of the treatment. The article provides an overview of current scientific data on the mechanisms of ischemic and reperfusion injuries at the molecular-cellular level and describes the current methods of their detection. Experimental and clinical study of the molecular-cellular mechanisms of ischemic-reperfusion injury of the renal tissue made it possible, first, to determine the main targets of alteration (cytolemma, mitochondria, lysosomes), and second, to establish its consequences, among which the most important are hypoergosis, DNA damage, simultaneous activation of intracellular systems of the suicidal program and induction of electrical breakdown of membranes of target nephrocytes; thirdly, to reveal the range of possibilities for limiting the consequences of hypoxia and/or re-oxygenation, among which interference in the metabolism of purines, measures ensuring the preservation of colloid osmotic pressure inside and outside the cell and membrane stabilization, antioxidant defense and inhibition of cysteine proteinases, etc. However, despite the advances in understanding the pathogenesis of cell damage, including ischemic-hypoxic injury, the problem of intraoperative ischemia-reperfusion safety remains relevant.

According to the World Health Organization, pathologies associated with ischemia/reperfusion occupy the leading position in the structure of mortality. The efficiency of localized kidney cancer surgery is limited by the damaging effects of prolonged warm ischemia and reperfusion. Ischemia/reperfusion damage to renal tissue may be related to changes in the expression profiles of pro- and antiapoptotic genes. Here, we have presented the longitudinal expression profiles of apoptosis-related genes in tissues of left and right (intact) kidneys of male rats exposed to unilateral ischemia followed by reperfusion. The profiles have been assessed at time points of 1, 3, and 48 h after the ischemic/reperfusion exposure by RT-qPCR quantification of mRNAs encoded by 13 genes, including BAX, p53, AIFM1, APAF1, CASP8, CASP3, CASP9,CASP7, MDM2, BCL2, CIAP1, XIAP, and ICAD, after normalization with respect to a reference gene ACTB. The study revealed a shift in the expression of pro- and antiapoptotic genes toward the predominance of proapoptotic processes, as was evinced by the increase in expression detected for the BAX, p53, AIFM1, APAF1, and CASP8 genes. One hour after the reperfusion, activation of mitochondrial, or intrinsic apoptosis was detected, while р53-dependent and extrinsic, i.e., receptor-driven, apoptosis joined at later time points. Changes in the level of expression of caspase 7 (CASP7)-encoding mRNA have only been detected 48 h after the restoration of blood flow. Changes have been observed in the transcription of pro- and antiapoptotic genes in tissues of both kidneys, which suggests the involvement of the contralateral kidney in systemic pathological process that develops during unilateral ischemia/reperfusion.

The objective of the present study was to elucidate the specific features of amlodipine distribution in the organism of the warm-blooded animals (rats) following a single intragastric administration of the poisonous substance at a dose of 686 mg/kg b/w/ (LD50). Amlodipine was isolated from the blood and various organs of the animals by means of acetone extraction and purified on the silica gel column (100/160 mcm) with the elution by an ethanol-hexane (7:3) mixture. The identification and the quantitative measurement of amlodipine were performed with the use of the TLC, GC-M, and UV-spectrophotometry. The study has shown that unmetabolized amlodipine was present in large amounts in the internal organs and blood of the poisoned animals. The principal organs of its accumulation were the stomach, kidneys, and blood.

The metabolic profile of plasma of white non-linear rats was investigated under normal conditions and after chronic inhalational exposure to low doses of aliphatic hydrocarbons with the number of carbon atoms from 6 to 10. Metabolic profile was determined with combination of gas chromatography-mass spectrometry and high performance, high resolution liquid chromatography-mass spectrometry with subsequent use of chemometrical methods for data treatment and presentation. It was shown that continuous 90-day exposure to a mixture of C₆-C₁₀ saturated hydrocarbons at concentration of 160 ± 20.5 mg/m³ results in various impairments of metabolic processes in liver and kidneys. Exposure to hydrocarbons at doses of 31.4 ± 5.6 mg/m³ and 5.2 ± 1.8 mg/m³ evoked significantly smaller changes. Novel metabolic markers of the toxic effect of low concentrations of C₆-C₁₀ aliphatic hydrocarbons were revealed. The ratio of concentrations of pyrophosphoric and oxalic acids in rat blood plasma was found to be the most sensitive marker called <>. A hypothesis is put forward about the redox balance violation as the leading pathogenetic mechanism of neuropathies and concomitant pathologies associated with hydrocarbon chronic intoxication.

In experiments with female Wistar rats it was shown that analogs of neurohypophysial hormones administered to gastrointestinal tract preserved their specific physiological activity - they increased solute-free water reabsorption and urinary sodium and potassium excretion. Doses of deamino-vasotocin exerted antidiuretic and natriuretic effects following its oral administration were 50 and 200 times higher compared to maximal effective ones after intramuscular injection. Inhibition of gastrointestinal proteases by aprotinine enhanced effects of nonapeptides; the amount of peptide absorbed from the intestine under these conditions was approximately 0.5 % of orally introduced substance. In contrast to analogs of neurohypophysial nonapeptides, glucagon-like peptide-1 mimetic (exenatide) did not exert its physiological effects after oral administration, whereas it increased urinary sodium and potassium excretion following intramuscular injection.

Results of treatment of 40 patients, suffering diffuse peritonitis in a terminal stage, were analyzed. In 20 patients (main group) the abdominal cavity sanation was done, using superoxyddysmutase solution. Concentration of uric acid, urea, creatinine, general bilirubin, C-reactive protein in the blood serum have had normalized more rapidly, than in a control group, witnessing satisfactory renal function present.

Atherosclerosis is one of the most common causes of death worldwide. Epidemiology studies firmly established an inverse relationship between atherogenesis and distorted lipid metabolism, in particular, higher levels of total cholesterol, an accumulation of CH-laden macrophages (foam cells), and lower plasma levels of antiatherogenic high density lipoprotein (HDL). It is believed that the reverse cholesterol transport, a process that removes excess cholesterol from peripheral tissues/cells including macrophages to circulating HDL, is one of the main mechanisms responsible for anti-atherogenic properties of HDL. The key proteins of reverse cholesterol transport-ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1)-mediate the cholesterol efflux from macrophages and prevent their transformation into foam cells. This review focuses on the role of ABC transporters A1 and G1 in the pathogenesis of atherosclerosis.

The aim of the present study was to compare effects of glucagon-like peptide-1 (GLP-1) mimetic exenatide on glucose and water-salt homeostasis in animals with different level of renal tubular proximal reabsorption - rats (Rattus norvegicus) and frogs (Rana temporaria). Following glucose tolerance test, in rats exenatide promoted rapid recovery of normoglycemia, whereas in frogs delayed this process. In water-loaded rats exenatide essentially augmented solute-free water clearance and enhanced natriuresis in furosemide-treated rats.-In frogs exenatide did not alter urinary flow rate, urinary sodium excretion and solute-free water clearance under water diuresis and furosemide treatment. It is suggested that the invol- vement of GLP- 1 in regulation of water-salt homeostasis in mammals should be preceded by key evoluti- onary transformation - increase in glomerular filtration rate and proximal tubular reabsorption.

Emotional stress plays a significant role in the processes of the development of arterial hypertension, especially in the presence of genetic predisposition. The origin and maintenance of hypertensive status during stress development can be activated by the sympathetic nervous system. An increase in sympathetic stimulation can, in turn, result in a change in the functions of kidneys, which provide fluid and electrolyte balance of the organism. A comparative study of the mRNA expression level of catechol-o-methyltransferase (Comt), mineralocorticoid receptor (Mlr), and β-subunit of epithelial sodium channel (β-ENaC) genes was conducted on the kidneys of hypertensive ISIAH rats and normotensive WAG rats at rest and after the effect of emotional stress. The discovered changes in the expression level of the selected genes confirm their involvement in increased sympathetic stimulation of the kidney, along with changes in the function of kidney regulation of fluid and electrolyte balance, which is an important factor of the development of sustained hypertension in the ISIAH rats strain.

The aim of the study was to evaluate the safe doses of commercially available nanosized colloidal silver (NCS), stabilized with polyvinilpirrolidone (PVP, food additive E1201) when administered in gastrointestinal tract of rats in the 92-day experiment in terms of the morphological changes in the internals of animals. The sample studied contained non-aggregated nanoparticles (NPs) of silver belonging to size fractions with a diameter of less than 5 nm, 10-20 nm or 50-80 nm. 80% of NPs were inside the range of hydrodynamic diameters 10.6-61.8 nm. The preparation of NCS was administered to growing male Wistar rats. (initial body weight 80 ± 10 g) for 1 month by intragastric gavage and then consumed with food at doses of 0.1, 1.0 and 10 mg/kg of body weight based on silver. The control animals received water or vehicle of nanomaterial--water solution of PVP. After withdrawal of animals from the experiment by exsanguination under ether anesthesia organs (liver, spleen, kidney, ileum) were isolated and their slides were prepared by standard methods following 'by staining with hematoxylin-eosin. Analysis was performed in light optical microscope equipped with a digital camera at a magnification from 1 x 100 to 1 x 1000. It was shown that the experimental animals treated with the NCS developed series of morphological changes in the tissues of the internal organs (liver, spleen and kidney) with the elevation of the range and severity of structural changes with increasing doses of silver. The most sensitive target of NCS action was apparently liver, which has already shown at a dose of 0.1 mg of silver NP/kg of body weight marked eosinophilic infiltration of portal tracts, which was accompanied at doses of 1.0 and 10.0 mg/kg by the emergence of medium and large-drop fat vacuoles in the cytoplasm of hepatocytes, swelling and lympho-macrophage. infiltration of the portal tracts. Detectable changes can be regarded as symptoms of inflammation of hepatocytes, at least, at a dose nanomaterial of 1.0 mg/kg body weight or more. Relative intensity of morphological changes in the internal organs correlated with published data on the biodistribution of silver NP administered to the gastrointestinal tract. It is concluded that the threshold dose corresponding to the minimum adverse effect of NCS is, according to the study of the above, no more than 1.0 mg/kg of body weight based on silver.

The paper investigates the specific features of chronorhythmologic changes of the ion-regulating function of the kidneys under the hypofunction of the pineal gland. For the study of hypofunction of the pineal gland, animals were maintained under constant light stimulation during 7 days. It has been established that the hypofunction epiphysis point out disturbances of the phasic structure of the ion-regulating function in relation to chronograms of the intact group of rats. In terms of physiological pinealectomy observed in- crease in the excretion of sodium ions (6,11±0,81 mmol/h) and the concentration of this cation in the blood plasma remained elevated around the clock. The obtained results indicate significant changes of integral characteristics of the rhythms of electrolyte metabolism and the important role of the pineal gland in ensuring physiological homeostasis.

Lipoprotein glomerulopathy (LPG) is a rare disease characterized by specific histological, immunomorphological, and ultrastructural changes. The main pathomorphological signs of LPG are lipoprotein thrombi in the lumen of the capillary loops, proteinuria, and dyslipoproteinemia as an increased concentration of apolipoprotein E (phenotypes E2/E3, E2/E4). A patient aged 47 years had nephrotic syndrome with a daily protein loss of 12.4 g/ day. Light optical microscopic examination of a renal biopsy specimen revealed Sudan III-positive, weakly PAS, and eosin-positive friable thrombi in the lumen of the capillary loops. No deposits of immunoglobulins were immunomorphologically detected in thrombotic masses. The ultrastructure of thrombotic masses was composed of granular masses with numerous vacuoles that formed concentric layers. Thus, LPG was diagnosed as a manifestation of type 3 hyperlipoproteinemia that had characteristic pathological, clinical, and laboratory signs of this disease.

The study was organized to provide additional characteristic of chronic dysfunction of renal allo-transplant using such biomarkers of serum and urine as enzymes (alanine aminotransferase), aspartate aminotransferase, gamma- glutamiltransferase, alkaline phosphatase, N-acetyl-β-D-glucosaminidase, interleukins (IL-2, IL-8, IL-10), beta-2- microglobulin. The chronic dysfunction of renal allo-transplant is characterized by increasing of concentration of IL-10 and beta-2-microglobulin in serum and increasing of concentration of beta-2-microglobulin, IL-2, IL-8 in urine and increasing of activity of N-acetyl-β-D-glucosaminidase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamiltransferase as compared with patients with satisfactory function of renal allo-transplant. The multivariant logistic regression analysis established that only activity of N-acetyl-β-D-glucosaminidase in urine was reliably independently related to chronic dysfunction of renal allo-transplant. It is assumed that increasing of concentration of beta-2-microglobulin in serum testifies glomerular dysfunction and in urine--tubular dysfunction of renal allo-transplant. The enzymeuria indicates continuing damage of epithelium of proximal tubules of nephron. The classification of patients with satisfactory function and chronic dysfunction of renal allo-transplant established that the highest indicators of square under ROC-curves had concentration of beta-2-microglobulin in serum (0.858 ± 0.061) and urine (0.733 ± 0.079) and activity of N-acetyl-β-D-glucosaminidase in urine (0.701 ± 0.061). To specify diagnosis of chronic dysfunction of renal allo-transplant the most useful (ratio of likelihood of positive result 10 and 11 correspondingly) are tests of beta-2- microglobulin in serum (more than 8.55 mkg/ml) and N-acetyl-β-D-glucosaminidase/creatinine in urine (more than 34 nmol/(sl)/ mmol/l). These discoveries require further validation and confirmation by implementation of morphological analysis of bioptat of renal allo-transplant.

Chronic kidney disease (CKD) increases the risk of all-cause mortality and cardiovascular disease as well as progression to end stage kidney failure. The relationship of glomerular filtration rate (GFR) and albuminuria with clinical outcomes in the general population are revealed. This allows to present levels of GFR and microalbuminuria (MA), which increases the risk of mortality. Renal dysfunction, which revealed by the level of GFR and creatinine, can have definite role in hemodynamic changes and heart failure progression. For mentioning the interaction of cardiovascular and renal diseases the cardiorenal syndrome (CRS) term was introduced, with its classification on 5 types, according to the presence of acute/chronic heart failure and primary/secondary origination of heart and kidney injury. We study interrelations between echocardiographic data of left ventricular remodeling, MA level and degree of renal dysfunction in 115 patients with CRS. MA was measured with diagnostic strips, contractile function of left ventricle (LV) - by echocardiography and GFR was assessed by Cocroft-Gault method. The association between MA with decreased GFR and elevated creatinine levels and its connection with increased LV myocardial mass and preclinical disturbances of LV systolic function was revealed. We determined direct correlation between MA and myocardial mass index and indirect - between ejection fraction of LV and MA. Obtained data allow to mention the level of MA (25,4±5,8 ng/ml) in which there is more probability of LV contractile functional changes, which will allow early prediction and prevention of CRS progression and pathogenetically approved pharmacotherapy organization in this category patients.

147 patients who underwent urinary intestinal diversion from 2004 to 2014 were selected for the retrospective study. The authors carried out a comparative analysis of rates of complications that arise from the direct ureterointestinal anastomosis. The mean age of patients was 54.2 ± 3.0 (36-69) years. 60 (40.81%) patients of group 1 underwent Nesbit's direct ureterointestinal anastomosis, while in 87 (59.19%) patients of group 2 Wallace-1 and Wallace-2 anastomoses were performed. Average follow-up was 5.6 (2-10) years. Strictures of ureterointestinal anastomosis were detected in 2 (3.38%) patients of group 1 and in 1 (1.14%) patient of group 2. In all cases re-anastomosis was performed. The maximum postoperative concentration of serum creatinine in both groups was 231 mmol/l. According to radioisotope kidney scan, no differences in accumulative and excretory renal functions between two groups of patients were recorded. No kidney stone formation in both groups of patients during the follow-up period was observed. No ureteral reflux above grade 3 was noted. The clinical manifestation of reflux pyelonephritis was observed in 3.5% of the patients. Acute pyelonephritis was cured by antibacterial therapy.

The article presents results of identification of indicators of cytokine status in 58 patients with glomerulonephritis using solid-phase immunoenzyme analysis. It is established that in patients with glomerulonephritis the level of pro-inflammatory and anti-inflammatory cytokines (IL-lβ, IL-2, IL-10 and Ra-IL-1β) circulating in blood is augmented. The differences are established concerning cytokine status of patients depending on clinical type of disease. The level of production of IL-10, correlating with glomerular, tubular and erythropoietic functions of kidneys significantly effected formation of various clinical types of glomerulonephritis.

In experimental studies the sequence of vitals series lesion is established at various forms of acute experimental pancreatitis (edematous pancreatitis, a pancreatonecrosis). It is shown that one of the first in pathological process involves an intestine, then - a liver, further - kidneys. It is established that at acute pancreatitis the basis of a target organs lesion is membranodestruktivny process due to excess activity of lipids peroxidation processes and phospholipase systems which are registered not only in a blood plasma, but also in tissue structures of the studied organs - an intestine, a liver, kidneys (systemic distress damages of oxidative and phospholipase induced character) acts.

Heavy metals are the most dangerous anthropogenic pollutants human environment. With an extensive range of pathological effects of heavy metals lead to the development of irreversible changes in the tissues of living organisms and systems. The main target organ destructive influence of metals are the kidneys, which is associated with the peculiarities of running these bodies physiological functions. There are many mechanisms allowing heavy metals to exercise their pathogenic effects on the body, the most significant of which is the mechanism of activation of free radical oxidation, due to the inherent heavy metals prooxidant activity. On this basis, the main objective of the pilot study was to investigate the influence of lipid peroxidation in the kidney function. To determine the functional state of the kidneys was performed to study the basic processes of urine formation, protein excretion and urine osmolarity. The intensity of lipid peroxidation was judged by the concentration of malondialdehyde and hydroperoxide in the blood of animals. Results of the study revealed that long-term administration of heavy metals in experimental animals leads to the development of a powerful oxidative stress, characterized by an increase in the content of lipid peroxidation products in the blood of animals. The paper found that the activation of lipid peroxidation in the conditions of long-term administration of heavy metals associated with the development of marked disorders of renal function. A strong antioxidant effect of melatonin in long-term poisoning with heavy metal salts reduces the activity of lipid peroxidation, which in turn weakens the pathological effects of xenobiotics on renal function. The findings suggest that the activation of heavy metals, lipid peroxidation is one of the mechanisms leading to the development of pathophysiological changes in the kidneys.

Aim: to investigate the relationship between the levels of NGAL and IL-18 in.blood, urine and clinical, morphological parameters reflecting renal tubulointerstitial tissue damage (TTD) in patients with chronic glomerulonephritis (CGN)., Materials and Methods: We examined 81 patients with CGN. Patients were divided into 2 groups according to the presence of arterial hypertension (AH). Levels of NGAL and IL-18 in blood and urine were determined by the immuno-enzymic method. Data of renal morphological study were used for the analysis of TTD., Results: In patients with CGN and AH we observed more pronounced morphological changes of renal TTD, what coincide with higher levels of NGAL and IL-18 in blood and urine. We found correlations between markers and morphological changes, what allow to use NGAL in blood and urine, IL-18 in blood to estimate renal TTD in CGN., Conclusions: NGAL in blood most accurately reflects interstitial fibrosis (IF) and tubular basement membrane changes; NGAL in urine--tubular epithelium dystrophy. IL-18 in blood is an indicator of dystrophy and necrosis of the tubular epithelium, IF.

The diagnosis of hyperglycemia was based on the fasting plasma glucose, the 2-h value in the 75-g oral glucose tolerance test and the determination of glycated hemoglobin. The purpose of investigation is determination of glycated hemoglobin by patients with the risk of critical condition. For it the three patients groups were investigated: with cerebrovascular diseases, with hyperasotemia and with the renal insufficience. We discoved that hyperglycemia and HbA1c formates important factor in the change of the tone of cerebral arteries. Hyperasotemia makes ponderable percent of distribution in the general population of people. The level of glycated hemoglobin by patients with latent renal insufficience was increased. The determination of HbA1c can use for patients with critical conditions.

The endogenous intoxication of organism can be a primary cause of changing in content of protein molecules with enhancement of their capacity to adsorb microelements fastening conformation of proteins. Such an alteration add them antigen characteristics conditioning autoimmune damage of tissues, kidneys included. The most frequent syndromes (cases?) ofendogenous intoxication effecting kidneys pathology are presented.

Purpose: To assess ischemia-reperfusion injury of renal allograft by microdialysis., Design: A pilot, single-center; prospective study., Patients and Methods: The study included 7 patients (4 males and 3 females, average age was 46.71 ± 6.53 years) after cadaveric kidney allograft transplantation (CKA) under general combined anaesthesia., Conclusions: Microdialysis provides an opportunity of continuous monitoring of metabolic changes in the tissue of transplanted kidney. The main advantage of the monitoring by microdialysis is an opportunity of early identifying of ischemia-reperfusion complications. Thus, early assessment of CKA by microdialysis can be for the improving of patient's treatment in the early post operative period. Further clinical studies must be done to define the role of microdialysis.

Combined trauma ranks high among all traumatic injuries. It is supposed to be one of three leading causes of death in general population and the most frequent cause of death among 40 year olds. Combined trauma mortality rates in Russia amount to 59-65 per 100,000 population and the number of years of life lost due to combined trauma is 15-25. High traumatic injury rates with large percentage of multiple injuries, high mortality and disability rates make combined trauma a high priority problem. The aim of this study was to demonstrate the feasibility of detecting early impairment of renal function in patients with combined trauma. The serum cystatin C levels and blood chemistry values were evaluated in 40 patients with combined trauma. Most of combined trauma patients in the study group were found to have normal creatinine values (36 patients). In 55% of the patients the serum cystatin C was increased to greater than 30% above normal values. The serum cystatin C levels peaked within the first 3 days after injury and then decreased gradually. In 27% of patients high levels of the serum cystatin C remained elevated after 1 week following trauma. In 61% of patients diagnosed as having renal contusion the serum cystatin C levels were above normal values. Decreased levels of GFR measured by Rehberg's test were detected in only 4 patients, while estimated by Hock's formula - in 22 patients.

The paper analyzes data on how physical exercise as a standard test of cosmonaut's performance, affects the renal function and urine protein profile. The investication involved 10 normal human subjects. Following exercise, rate of renal excretion of proteins increased. The occurrence of 4 proteins out of 9 in urine did not alter and of 2 (alpha-methylacyl coenzyme A racemase and cubilin) increased; occurrence of 3 proteins (kallikrein-1, osteopontin and vitamin K-dependent protein Z) decreased. Out of 24 proteins with molecular weights higher than albumin, 7 were detected in urine after exercise more frequently, 6 with same frequency as before the test and none less frequently which demonstrates lowered selectivity of the glomerular barrier during exercise.

There were investigated morphofunctional indices of liver and kidney in male outbred rats in the dynamics of the 6-months consumption of water after its noncontact activation. There were studied 4 experimental groups of animals consumed waters named as "Anolyte" and in dependence on the activation time, 3 types of catholyte water ("Catholyte--5", "Catholyte--25", "Catholyte--40"). Moscow tap water settled for a week served as control. "Anolyte" water was found to increase in the kidney the number of hypertrophied gromeruli only in 6 months, while the consumption of "Catholyte--25" water and especially, "Catholyte--40" in 1 and 6 months caused the damage of liver and kidney, and for the index of alteration of renal glomeruli after 6 months of water consumption there was revealed the dependence on the activation time of "Catalytes".

The analysis of retainment and release kinetics of deposited in tissue structures calcium was made in the hypercalcemic conditions in 28 healthy volunteers (22 males and 6 females) of the age of 33 ± 6.5 years via drip infusion (Groups 1, 2) and in 9 individuals (3 males and 6 females) in 12 trials via stream infusion (Group 3). By the end of each hour after the termination of calcium infusion the amount of calcium retained in tissues was calculated (Mtis./kg); the parameters of its binding (specific buffer volume--β3 sp, association constant--Ka, number of binding centers--n) were established using the Langmuir and Scetchard coordinates. The Group 1 volunteers (n = = 12) showed a section of positive cooperativity (a direct regression on Sketchard coordinates, Hill coefficient 3.36 ± 1.63) and 2 sections of the consecutive calcium separation from one set of noninteracting centers. 5 volunteers of Group 2 and 8 volunteers of Group 3 demonstrated a slight calcium delivery to tissues after 1 hour of observation which then followed for 2 volunteers of Group 2 and for 2 volunteers of Group 3. Other volunteers of Groups 2 and 3 showed a release of tissue-deposited calcium via the mechanism of the consecutive separation from one set of noninteracting centers with βsp 3 times less and Ka 7 times higher than with the calcium infusion. The excretion of calcium in urine was the highest in Group 1 and the lowest in Group 3. The [Ca2+] and Mtis./kg values were normalized in Groups 1 and 2 the next morning and in Group 3 after 2-3 hours of observation. An assumption was made about the relationship between the tissue and kidney [Ca2+] normalizing mechanisms with hypercalcemia.

Effects of neurohypophysial nonapeptides of vertebrates (vasopressin, vasotocin, and their synthetized analogues) on urinary magnesium excretion were studied in rats. Neurohypophysial hormones and their analogues at doses stimulating V2-receptors (0.0001-0.001 nmol/100 g BW) produced antidiuretic effect and reduced urinary magnesium excretion. At the higher doses activating V2- and V1a-receptors (0.025-0.1 nmol/100g BW), vasotocin and its analogues (deamino-vasotocin (dAVT), deamino-Thr4-vasotocin, deamino-hArg8-vasotocin, deaminomonocarbo-vasotocin) enhanced excretion of magnesium and sodium ions. Direct relation between increase in renal excretion of sodium and magnesium ions was found under these conditions. dAVT induced 10 times lesser increase in magnesium excretion after administration of a V1a-receptor antagonist. An antagonist of V2-receptors did not affect the dAVT-induced magniuresis. The obtained data suggest that V-receptors take part in regulation of magnesium transport in rat kidney.

The experiment on white rats was targeted at the examination of influence of statins (atorvastatin, lovastatin, simvastatin) under the conditions of acute renal failure, caused by rhabdomyolysis. Renoprotective effects of statins were demonstrated by reduction of hyperazotemia and proteinuria and improvement of renal excretory function, which correlated with antioxidant properties of drugs.

The influence of the organospecific peptides--kidney tripeptides T-31 and T-35, pineal tetrapeptide epitalon on the main mechanisms of kidney injury caused by experimental rhabdomyolysis--toxic injury of tubular cells, development of oxidative stress and energetic misbalance, leading to significant disturbances of the functional state of kidneys and development of acute kidney failure was studied. The renoprotective effect of oligopeptides realized by impact on all of the indicated mechanisms of kidney injury and confirmed by correlation between them was estimated.

Chronic 6-month experiment was carried out in rats, which received drinking water with multi-walled carbon nanotubes (MWCNTs), diameter of 15-40 nm, length ≥ 2 mkm) or activated charcoal (AC, diameter of 10-100 mkm), blood samples of the animals were used for assessment of biochemical markers. Both coal compounds induced the appearance of signs of oxidative stress 2 weeks after the beginning of the experiment and alteration of serum markers of liver and renal damage, as well as changes of cortisol and protein serum concentrations later Thus, despite of known high (asbest-like) inhalation toxicity of carbon nanotubes in comparison with other carbon allotrops (fullerenes and black carbon), we have found similar effects of MWCNTs and carbon microparticles in orally treated rats.

The influence of deuterium depleted water on the body of different rats generations was investigated in physiological conditions. As a result of this study it was established that the most significant and rapid reduction in D/H equilibrium was observed in plasma (by 36.2%), and lyophilized kidney tissues (by 15.8%). Less pronounced deuterium decrease was characteristic of liver tissue (9.3%) and heart (8.5%). Stabilization of the isotopic exchange reaction rate was fixed in the blood and tissues of rats, starting from the second generation. At the same time when deuterium depleted water (40 ppm) was used in dietary intake, the change in morphological and functional parameters in laboratory animals associated with the processes of adaptation to the effects of substress isotopic D/H gradient was also noted. The study shows that modification of:only drinking water intake regime can't significantly change the deuterium content in tissues of metabolically active organs, because of the concurrent deuterium receipt in food substances of plant and animal origin.

The influence of deuterium depleted water with the modified isotope composition on an organism of animals is studied in physiological conditions and development of chronic endogenous intoxication of hepatorenal genesis. The influence of this water on isotope composition of plasma and tissues (the liver and kidneys) in laboratory animals is shown. The impact of this water on biochemical indicators (AST, ALT, alkaline phosphatase, creatinine, bilirubin) and dynamics in body weight of laboratory animals within 42 days is established. As a result of studies the possibility of the preventive use of deuterium depleted water for correction of metabolic processes is shown in various conditions of the functional system of the body's detoxification.

Resistant hypertension occurs in up to 15% of patients with arterial hypertension in Russia. Medical treatment of resistant hypertension must include minimum 3 medications with maximum or maximum tolerated doses besides one of the medications must be diuretic. According to department of arterial hypertension of the Burdenko Main Military Clinical Hospital to achieve the target levels of arterial blood pressure it was necessary to prescribe 4-5 components antihypertension therapy in patients. Authors suggested an algorithm of diagnosis and treatment of patients with resistant hypertension with the help of surgical method. This method is based on decreasing of sympathic nervous system activity by selective break of neuronal connections with the help of interventional intravascular radio-wave ablation. Endovascular renal sympathetic denervation allows to effectively control arterial blood pressure, to optimize antihypertensive therapy, but this method does not cure from arterial hypertension.

The kinetics of ammonia, glutamine, and urea in the kidney has been studied in experiments on 203 white rats (females) at the end of chronic tetrachloromethane (CCl4) exposure (65 days) and within 14 days after cessation of CCl4. It was found that on the 65th day of CCl4 administration the arterial hyperammoniemia is formed, which lasts for 14 days after the abolition of the toxin. This is accompanied by an increased excretion of ammonia in the urine and an increase in its concentration in the blood of renal veins, which does not prevent its accumulation in renal tissue. In chronic CCl4-hepatitis model are the changes of glutamine concentration in arterial blood are developing by type of hypo- and hyperglutaminemia. CCl4 stimulates accumulation of glutamine by the kidneys at the end of exposure and at early stage of the recovery period. Toxin cessation activates processes which are stabilizing the normal concentration of glutamine in the kidney by changing glutamine incretion from kidney to renal blood flow. Long-lasting CCl4 exposure increases the concentration of urea in the arterial blood and its urinary excretion. Simultaneously urea reabsorption is activated in the kidneys, which contributes to an increase in its concentration in the blood of the renal veins.

A comparative analysis of the effect of silver nanoparticles (SNP) with a diameter of 14 nm and silver sulfate (SS) on biochemical indices of the state of the organism under the administration of preparations with drinking water to mice F1 CBAxC57Bl (from 0.1 to 500 mg Ag/l for 2 weeks) and nonlinear rats (from 0.01 to 5 mg Ag/l within 6 months) has been performed In the experiment on mice there was found an increase in activity of glutathione reductase (GR) in erythrocytes under the administration of both drugs and reduction of antiradical activity of serum--under the introduction of SNP only. The administration of low doses of SNP in the experiment on rats caused much less pronounced changes in serum markers of the state of the liver; kidneys, protein and lipids metabolism in comparison with equivalent doses of the SS, that as a whole with the qualitative differences on GR activity in erythrocytes satisfactorily was explained by activation of phagocytic cells with nanoparticles. Thus, for the first time the SNP biological effects in animals were shown to be caused both by the exposure to solubilized Ag+ ions and by the response of cells to the surface of the nanoparticles themselves.

Histochrome is the medicinal form of echinochrome (2,3,5,6,8-pentahydroxy-7-ethyl-1,4-naphthoquinone). The drug pharmacodynamics and its relationship with metabolism, which was revealed in previous investigations, predetermined the aim of this work: to study excretion of echinochrome and its possible metabolites in urine of rats. Histochrome was introduced to Wistar rats (n = 10) subcutaneously in a dose of 10 mg/kg. Naphthoquinone derivatives were extracted from the acidified urine by ethyl acetate and analyzed by high performance liquid chromatography with UV detection (HPLC/UV) and mass-spectrometric detection (HPLC/MS). It was established that histochrome is completely metabolized in an organism and excreted by kidneys in the form of 3-methoxy-2,5,6,8-tetrahydroxy-7-ethyl-1,4-naphthoquinone and 2-metoxy-3,5,6,8-tetrahydroxy-7-ethyl-1,4-naphthoquinone.

The renal osmoregulatory function was studied in patients with type 2 diabetes mellitus (DM). The renal response to water loading (0.7% b.w.) and simultaneous exenatide (byetta) injection (5 microg) exhibited variation and was dependent on the degree of hyperglycemia. Effective solute-free water excretion was observed in patients with well-controlled DM (HbAlc 6.0 +/- 0.1%), in which CH20 changed from -0.67 +/- 0.2 mL/min to 0.72 +/- 0.2 mL/min. This reaction was absent in patients with poorly controlled DM (HbAlc 8.8 +/- 0.6%) and the process of solute-free water reabsorption prevailed: -CH20 = -1.06 +/- 0.1 mL/min in control period vs. -0.99 +/- 0.1 mL/min after treatment. Thus, byetta increases the efficiency of osmoregulation and accelerates the excretion of excess water in patients with compensated carbohydrate metabolism.

In subchronic intoxication via repeated intraperitoneal injection of copper oxide nanoparticles (diameter 20 nm, 19 times in dose of 10 mg/kg of rats, 3 times per week), findings are that oral intake of bioprotectors complex (pectine, polyvitamin and polymineral preparation, sodium glutaminate, glycine, acetylcysteine and fish oil preparation with high content of unsaturated fatty acids of omega-3 group) decreases copper accumulation in viscera (including statistically significantly in spleen) and slows development of pathologic changes in liver, brain and kidneys. With that, genotoxic effect of nanocopper also decreases--according to lower fragmentation of genome DNA in liver and spleen cells.

Immunofluorescence labeling of proteins with molecular mass of 27, 38, 40, 50 and 65 kDa obtained from serum of patients with autoimmune disease demonstrated different patterns (small clusters or granules) in interphase nuclei of pig kidney cells. It was remarkable that there was no staining inside the nucleoli, but the proteins immunoreactivity was detected around them in the regions of perinucleolar chromatin. Moreover, expression of nucleolar proteins, such as fibrillarin and B23, was found only in nucleoli. After extraction of DNA, PNA and histones, the proteins with molecular mass 27 and 38 kDa were found in the periphery of residual nucleoli, and proteins with molecular mass 40, 50 and 65 kDa had similar localization and were also present in karyoplasm of cells as small clusters. According to our data, nucleolar protein, fibrillarin, was distributed regularly throughout the whole volume of residual nucleoli. At the same time, B23 protein was revealed only at their periphery, where perinucleolar chromatin had localized before treatment. Thus, it has been revealed that the proteins of nuclear matrix with molecular mass 27, 38, 40, 50 and 65 kDa, as well as nucleolar protein B23 are the parts of perinucleolar chromatin, which could be considered as special chromosomal domain associated with the functioning of the nucleolus.

We studied the influence of structural and functional disorders in cardiovascular and renal system and metabolic disturbances on perinatal outcomes in pregnant women with chronic arterial hypertension. The study included 100 women with these pathologies and 30 patients with physiological pregnancy. Comprehensive evaluation of the cardiovascular system, metabolic status, and perinatal outcomes was undertaken. The results indicate that atherogenic dyslipidemia is significantly associated with the reduction of body mass while glomerular filtration rate, concentric and eccentric left ventricular hypertrophy with the decrease of both weight and height of the newborns.

Repeated intraperitoneal injections of nickel and chromium (VI) into rats appeared to demonstrate that the combined subchronic toxicity can be additive or vary (mostly to subadditivity) in accordance with effect on which they are evaluated. With moderate general toxic effects, the studied combination has marked genotoxicity with additive effect. The studies demonstrated reciprocal influence of nickel and chromium on accumulation of the second metal in some organs (especially, in spleen), but not on its renal excretion.