THE AIM of the investigations was to study the association of aldosterone synthase gene polymorphism with the value of concentration of plasma aldosterone (CPA), the degree of arterial hypertension (AH) and left ventricle myocardium remodeling (LVR) in patients with the V stage of chronic kidney disease (CKD) on program hemodialysis (HD). PATENTS AND METHODS. An examination of 84 patients with the V stage of CKD was carried on. Mean age of the patients was 51± 15 years. Mean duration of HD therapy was 7.7 ±0.5 years. In 55 patients (65.5%) the course of the main disease was complicated by the development of arterial hypertension (AH). Mean duration of AH was 12.9±1 years. CPA was determined by an immune-enzymatic method. The state of the left ventricle (LV) was assessed by the volume and thickness of LV walls in diastole (cm), LV myocardium mass (LVMM, g) indexed to the body surface area (ILVMM, g/m²), the ratio of the wall thickness/diameter of the LV cavity. The remodeling type was determined as normal geometry, LV concentric hypertrophy, LV excentrtic hypertrophy and concentric remodeling. The polymorphous marker alleles – 344T/C of gene CYP11B2 were identified using the polymerase chain reaction. The amplification products were treated with restrictase. The data obtained were processed using the application package STATISTICA 6.0. The distinctions were considered reliable at p<0.05. RESULTS. In 21 patients (25%) the C/C genotype was determined, in 33 patients (39.3%) – C/T genotype and in 30 (35.7%) – the T/T genotype. In all the patients, irrespective of the nucleotide polymorphism, a sharp elevation of CPA was noted (in C/C genotype patients – 653.08±186.61, in C/T genotype patients – 454.92±78.77 and in T/T genotype patients – 587.94± 128.09 pg/ml, at the norm 10[1]160). C/C genotype patients have a higher level of SAP (141.1±2.8 mmHg) and DAD (91.3±1.5 Hg mm) compared to 135.6±2.1 (p<0.01) and 86.8±1.4 in C/T genotype patients (p<0.05) and 132.8± 1.9 and 81.1± 1.1 (p<0.01) in patients with T/T genotype. Furthermore, the patients with C/C genotype have greater thickness of the interventricular septum (1.39±0.09) compared to 1.24± 0.05 in patients with C/T genotype and 1.24±0.03 (p<0.05) in patients with T/T genotype, LVMM – 312.1±34.05 compared to 270.43±26.75 and 238.47±16.76 (p<0.05) respectively, and ILVMM – 186.2±21.25 compared to 270.43±26.75 and 238.47±16.76 (p<0.01) respectively. The greatest percentage of LV concentric hypertrophy (61.1%) corresponded to the C/C genotype carriers. CONCLUSION. An association of nucleotide polymorphism with the CPA value was not revealed. The carriers of the C/C genotype of aldesterone synthase have reliably higher AP, greater mass of the LV myocardium, index of the LV myocardium mass and the highest percentage of concentric LVH which is associated with a more unfavorable prognosis.

THE AIM of the work was to study morphological alterations in the kidneys in patients with primary arterial hypertension (AH) at different stages of the  developing  process. PATIENTS AND METHODS. Under investigation there were  19  patients with AH in whom puncture nephrobiopsy was performed. Mean age of the patients was 33.4±12.6 years. Among them there were 11 men (57.8%) and 8 women (42.2%). Mean duration of primary AH was 5.5±4.5 years. The patients were divided into 3 groups according to the duration of AH. The first group included 7 patients with AH duration 1.4±0.6 years. Mean age of the patients was 28.7±10.2 years. The second group included 6 patients with AH duration 4.5±0.9 years, mean age 42.3±5.1 years. The third group consisted of 6 patients; duration of AH 11.3±3.1 years.  Mean age of the patients 40.2±8.8. RESULTS. Light optic microscopy has revealed in the 1st group alterations first of all in the interstitial tissue seen as periglomerular fibrosis. In the second group the morphological picture, the same as in the first one, was supplemented with thickenings and fibrosing of the walls of the arterial type vessels, proliferation  of the smooth  muscle  layer of arterioles,  signs of subatrophy and atrophy in the channels,  greater symptoms of hydropic and protein dystrophy in nephrothelium. In the 3rd group there were signs of sclerosing glomerules, hypertrophy of intact glomerules,  mild mesangial hypercellularity,  paramesangial hyalinosis,  marked periglomerular fibrosis,  plasmatic impregnation of the interstitium and walls of the arterial type vessels. CONCLUSION. So, the sequence of the involvement of kidney ultrastructures in the pathological process was established in AH patients, consisting in a paramount lesion of the tubular interstitial tissue, then vessels and finally - glomerules.

THE AIM of the investigation was to determine the spread and influence of calcification of the mitral (MV) and aortal (AV) valves of the heart on its function in a group of examined dialysis patients and to find the factors associated with calcinosis of MV and AV, and connections of valve calcification with uremic osteodystrophy. PATIENTS AND METHODS. Under investigation there were 131 patients after Doppler-Echo CG, aged 51.7±12.6 years treated by hemodialysis (HD) during 77.7±75.6 months. IHD was found in 55.6% of the patients, heart failure (HF) in 50.0%. Intact parathyroid hormone (PTH), biochemical markers of inflammation (fibrinogen and C-reactive protein) were determined in all the patients in addition to ordinary investigations. The state of MVand AV according to Doppler-Echo CG were estimated as the norm, infiltration, calcinosis (of valve annulus or cusps).The presence of stenosis, regurgitation of MV and AV were also determined. The thickness of the intima[1]media complex (IMC) of the carotid artery was measured. The 24 hours’ monitoring of arterial pressure was performed in 88 patients and ECG monitoring in 100 patients. Bone mineral density (BMD) of three parts of the skeleton (lumbar vertebra, proximal part of the femur and forearm) was measured in 63 patients by the method of dual energy X-ray absorptiometry estimated by T-criterion and Z-criterion. The BMD value more than -1 was considered normal, from -1 to -2.5 as osteopenia (mild decrease of MBD), less than – 2.5 as osteoporosis (considerably decreased MBD). RESULTS. Calcinosis of the valves was detected in 38.9% of the patients: isolated AV calcinosis – in 3.8%, MV – in 13.0%, both valves calcinosis – in 22.1% of the patients. Stenosis of that valve was more often detected in patients with AV calcinosis (χ2= 19.8; p<0.001) and they had more pronounced regurgitation (t=3.16; p=0.003). MV calcinosis also promoted stenosing (χ2= 17.27; p<0.0001) and regurgitation (t=2.11; p=0.038). A comparison of the groups of patients which differed in the presence of valvular calcinosis has shown that patients with valvular calcinosis were older (Z=4.02; p<0.001), had longer dialysis treatment (Z=2.93; p=0.0034), had IHD more often (χ2=6.02; p<0.014), HF (χ2= 3.85; p=0.05), higher levels of PTH (Z=2.09; p=0.037) and alkaline phosphatase (Z=2.93; p= 0.0034), greater IMC thickness (Z=2.45; p=0.014), less values of forearm MBD (Z=1.98; p=0.048), higher values of C-reactive protein (Z=2.50; p= 0.016). In addition, patients with valvular calcification had greater size of the left atrium (Z=3.67; p= 0.001), higher flow rate through MV (Z=4.24; p<0.001) and AV (Z=3.79; p<0.001).CONCLUSION. Calcinosis of MV and AV of the heart was diagnosed in one third of the examined patients. A combination of calcification of the valves prevailed. Calcification of the valves was more often observed in older patients, with longer HD treatment, more pronounced hyperparathyrosis, inflammatory alterations, atherosclerosis. An association of valvular calcinosis with less BMD was found for the first time. Calcification of the valves was combined with greater frequency of IHD, HF, dilatation of the left atrium and speeding up the flows through AV and MV.

THE AIM of the investigation was to assess the antihypertensive effectiveness of interval normobaric hypoxytherapy (INBHT) in patients with combined pathology – chronic glomerulonephritis (CGN) and angina pectoris. PATIENTS AND METHODS. The investigation included 77 patients with combined pathology – angina on exertion and CGN. The first group consisted of 47 patients, who, according to recommendations of the European cardiological society (2006), were treated with nitrates, calcium channel blockers (CCB), antiaggregants , beta-adrenoblockers (BAB), statins, inhibitors of the angiotensin converting enzyme (by indications), diuretics (by indications) in combination with INBHT. The second group included 30 patients who were given only medicamentous therapy without INBHT. RESULTS. A comparison of the effects of the two therapeutic regimens on the values of arterial pressure has revealed more pronounced antihypertensive effects of the combination of medicamentous therapy with INBHT. The first group patients demonstrated less intensive decrease of heart rate than those treated without INBHT. The frequency of achieving the desired pressure level was 100% when medicamentous therapy was combines with INBHT, medicamentous therapy only – 77.7%. The rate of decreasing the systolic pressure proved to be higher when the medicamentous therapy was combined with INBHT, than without INBHT. Statistically reliable differences of systolic pressure were seen as earlyas in 3 hours after the beginning of the 24 hours monitoring of pressure. CONCLUSION. Combined therapy with INBHT allowed more effective control of arterial hypertension as compared with traditional medicamentous treatment of hypertensive syndrome.

THE AIM of the investigation was to assess the level of AP and the left ventricle hypertrophy index (LVHI), concentration of nitrates and sulfates in blood serum of spontaneously hypertensive SHR rats subjected to nephrectomy (NE) against the background of standard diet and low-protein soy diet (LPSD). MATERIAL AND METHODS. Experiments were fulfilled in male spontaneously hypertensive SHR rats with intact kidneys or subjected to 5/6 NE. The following investigations were carried out: 1.A control group (n=15) – sham-operated (ShO) rats receiving a standard diet (20.16% of the animal origin protein); 2. Animals (n=11) receiving the standard diet after NE; 3. ShO rats (n=10) receiving LPSD containing10% soy isolate SUPRO 760; 4. Rats (n=11) receiving LPSD after NE. In two months after NE and sham operation the following investigations were made in the animals: measurement of arterial pressure, heart rate, content of nitrates (NO₃¯, mg/l) and sulfates (SO₄²¯, mg/l) in blood serum, the degree of hypertrophy of the heart, left ventricle myocardium, liver, spleen. RESULTS. In SHR rats, receiving the standard diet, NE resulted in growing AP and LVHI as compared with controls. LPSD prevented the growth of mean AP and LVHI3 in the rats with NE. Soy diet decreased the hypertrophy index of the liver in ShO animals and NE rats as compared with the controls given the standard diet. No substantial differences in the level of NO₃¯ were found between the analyzed groups. CONCLUSION. LPSD including the soy isolate SUPRO 760 has a cardioprotecting effect in spontaneously hypertensive rats with experimental renal failure due to decreased myocardium hypertrophy and prevention of mean AP growth.

THE AIM of the investigation was to study in dynamics the state of the capillaries of glomerules of the superficial and juxtaglomerular nephrons and the ultrastructure of juxtaglomerular apparatus (JGA) of the kidneys after protein load and starvation. MATERIAL AND METHODS. The experiments were carried out in 30 white outbred male rats with body mass 120-140 g. Morphological investigation of the degree of opening the glomerular capillaries of the superficial and juxtaglomerular nephrons and the ultrastructure of JGA was made in a control group consisting of animals 1 day after intraperitoneal administration of 5.0 cm³ of 6% solution of albumin, after 3 days (the 3rd group) and after 1 and 6 days of starvation (the 2nd group). RESULTS. Dilatation of the afferent and constriction of efferent arteriols, increased portion of glomerules with greater degree of opening the capillaries (DOC) and activation of JGA cells were observed in a day after protein load. Three days later, with normalization of JGA structure, DOC of both superficial and juxtaglomerular nephrons was greater than in control animals. After 3 days of starvation DOC in both types of nephrons was increased and there was no activation of JGA. In 6 days DOC was increased and was synchronized in juxtaglomerular nephrons only; JGA was in hypofunctional state. CONCLUSION. The structural-functional features of the cells of JGA and glomerular capillaries of superficial and juxtaglomerular nephrons are naturally determined and directed to an increase of the functional reserve, maintenance of homeostasis, correspond to multi-level principle of self-regulation and integration, systemic principle of complicating the structures and functions of the kidney.

THE AIM of the investigation was to study in experiments the nephroprotective effect of arginine and glutargine in rats receiving cytostatic ifosfamide. MATERIALS AND METHODS. The nephrotoxic effects of ifosfamide were studied in white rats under conditions of 5% water diuresis in 7 days after daily administration of the cytostatic (5 mg/100 g b.m). Protective effects of arginine or glutargine were studied under conditions of water diuresis after the 7-day combined administration of ifosfamide and one of the substances. RESULTS. It was found that administration of ifosfamide to white rats during 7 days caused a moderate decrease of glomerular filtration rate and the values of standardized per 1 ml of the glomerular filtrate of excretion of osmotically active substances and proteins. In its turn, a combined administration to the animals of glutargine and arginine contributes tore-establishment of the glomerular filtration rate and normalization of transport of osmotically active substances and proteins. CONCLUSION. The nephrotoxic effects of glutargine and arginine are realized at the channel and glomerule level, and glutargine and arginine decrease the degree of kidney lesion.

THE AIM of the investigation was to study effects of extra low doses (10⁻¹⁰ – 10⁻¹⁴ mol/l) of 20 coded amino acids and their metabolites on the development of organotypical culture of rat testes. MATERIAL AND METHODS. The testes of 3 months old Wistar rats were divided into explants (1 mm³ fragments). The explants were placed in a Petri dish onto collagen and cultured in a CO₂-incubator in nutrient medium. Three days later the growth zone consisting of Leydig cells, Sertoli cells and spermatozoa was formed. For a quantitative assessment the area index was determined as the ratio of the total explant area to the central zone area. RESULTS. Reliable effects on the area index more than in one concentration was noted in 6 out of 20 coded amino acids: isoleucine (31±6%), lysine (25±4%), arginine (26±5%). None of the structural analogues of isoleucine (leucine, norleucine, valine) proved to be similarly effective. From all metabolites of L-arginine the testes growth is stimulated by L-ornitine (26±4%), urea (31±4%), creatine (20±3%); and L-citrulline (22±3%); and inhibited by nitric oxide (nitroglycerine – 100%). Glutatione eliminates antiproliferative effects of nitric oxide (25±7% vs 13±3% in concentration 10⁻¹³ mol/l) and thus increases effectiveness of L-arginine. In forming the mixture of the most active amino acids the arginine concentration must be 10 times more than the concentration of L-ornitine and creatine, but 10 times less that the concentration of L-lysine, L-isoleucine and L-citrulline. CONCLUSION. L-isoleucine, L- arginine and L-lysine are the most perspective amino acids for treatment of male infertility in clinical practice. It was first proved that L-isoleucine is maximally active for growth of testes. Nitric oxide is the only L-arginine metabolite with antiproliferative effect. A combination of L-arginine with glutathione eliminates the toxic effect of nitric oxide. A share correlation of amino acids necessary for maximal stimulation of the testes is established.