[Postgenomic and structural changes in the myocardia of Wistar rats fed a high-salt diet].

The relationship between dietary sodium, hypertension, and cardiovascular injury is far from clear. One of the important links in this process can be microRNAs that have the ability to modulate gene expression at the post-transcriptional level. However, their role in this process has not been fully studied. In addition, further studies require the identification of structural changes in the myocardium in conditions of long-term consumption of a high-salt diet. The aim of the study was to evaluate the expression levels of nuclear transcription factor κB (NFκB), microRNA (miRNA)-21 and structural changes in the myocardium during long-term consumption of a diet containing 8% (high) sodium chloride in Wistar rats. Material and methods. 20 Wistar rats with initial body weight 280.5±42.7 g were divided into two equal groups. The high salt (HS) group received 8% NaCl in the diet, the control (NS) group received the standard diet (0.34% NaCl). After 4 months, systolic blood pressure was measured in rats using the cuff method on the tail; the myocardial mass index was assessed after dissection; histological and electron microscopic examination of the myocardium was performed, and the expression levels of miRNA-21 and NFκB in the myocardium were determined. Results and discussion. Consumption of a diet high in sodium chloride for 4 months did not significantly affect the level of systolic blood pressure in normotensive Wistar rats, but led to an increase in myocardial mass index by 25.0% (p<0.05). In the HS group, hypertrophy of cardiomyocytes and an increase in the wall thickness of arterial vessels were revealed. The area of perivascular fibrosis in rats of the HS-group was almost 1.8 fold higher than in the NS-group. In animals of HS-group, the relative levels of expression of NFκB (more than 2 times) and miRNA-21 (almost 6 times) increased compared with the control. It can be assumed that the negative impact on the cardiovascular system of high-salt diets is partially realized through NFκB-associated signaling pathways and miRNA-21 activation. Conclusion. In Wistar rats, long-term use of a high-salt diet results in myocardial remodeling that is not associated with changes in blood pressure. At the same time, the adverse effects of high salt intake on the myocardium are mediated, in particular, by postgenomic mechanisms, namely an increase in the expression levels of NFκB and microRNA-21.

[Urinary miRNA expression in cynomolgus macaques (Macaca fascicularis) fed high salt rations].

High food intake of sodium chloride is associated with damage not only the cardiovascular system, but also the kidneys. The mechanisms of the potential negative effects of high-salt diets on the kidneys have not been established. The aim of the study was to trace the changes in relative expression of miRNA-21, 203 and 133 in urine of cynomolgus macaques (Macaca fascicularis) fed high-salt diet with and without isolated soy proteins. Material and methods. The object of the study was 18 male cynomolgus macaques (Macaca fascicularis) aged 6-8 years with a body weight of 5.1-9.7 kg. The animals were divided in 3 groups (6 individuals each). The animals of the first (control) group received a standard diet (2 g NaCl/kg feed). The animals of the second group were fed high-salt diet (8 g NaCl/kg feed), of the third - high-salt diet combined with SUPRO 760 isolated soy protein (200 g/kg feed; instead of milk and egg proteins, corn gluten). Access to water was free. The follow-up period in this study was 4 months. In animals blood pressure (BP) and relative level of microRNA (miRNA) expression in urine were measured. Results and discussion. Keeping monkeys on the studied diets for 4 months did not lead to significant changes in systolic or diastolic BP compared with the initial level. In the control group, there were no distinct changes in the expression of miRNA-21 in urine during observation. In the other two groups, there was a significant increase (approximately equally) of this parameter in comparison with the initial values. Both high-salt diets resulted in a significant increase in the relative level of expression of miRNA-133 and miRNA-203 in urine compared to basal values. However, the increase in these parameters in the group of animals fed a high-salt diet in combination with soy isolate was significantly less than in monkeys fed only a high-salt diet. Conclusion. Possible, potentially negative effects of high-salt diets on kidney may be mediated by epigenomic mechanisms and partially modulated by the inclusion of isolated soy proteins in the diet.

[Aging and kidneys: problems in evaluating of the glomerular filtration rate in elderly.]

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 disease¼ in elderly solely on the base of GFR decline may be an inadequate approach and promote a kind of «nephrological ageism¼.

[Effect of protein load on kidney functions in patients with chronic glomerulonephritis]. / Vliianie belkovoi nagruzki na funktsional'noe sostoianie pochek u bol'nykh khronicheskim glomerulonefritom.

AIM: To study changes in renal function in response to protein loads in patients with chronic glomerulonephritis (CGN) who have normal renal function and initial uremia. MATERIAL AND METHODS: 63 CGN patients were divided into two groups: 40 patients of group 1 (17 males, 23 females, age 16-53 years, plasma creatinine-Pcr < 0.132 mmol/l); 23 patients of group 2 (10 males, 13 females, age 18-57 years, Pcr > 0.132 mmol/l). Renal functional reserve (RFR) was assessed with oral soa isolate SUPRO 760 test (protein Techn. Int., USA), 1.0 g of protein per 1 kg of ideal body mass. By three 2-h clearance periods measurements were made of RFR, absolute and fractional excretion, concentration indices and clearances of creatinine, urea, electrolytes, osmolality. All the parameters were referred to the standard body surface. RESULTS: RFR was intact in 14 patients of group 1 and 10 patients of group 2. In CGN without uremia with intact RFR, maximal Pcr corresponded to the highest values of minute diuresis and sharp increase of urea excretion, osmotically active substances. In CGN patients with uremia and intact RFR, development of hyperfiltration was accompanied with a significant rise in Pcr, minute diuresis, absolute excretion of urea and osmotically active substances. The rise in the latter two was much less active in CGN if RFR was absent. Multiple stepwise regression analysis showed that RFR intactness depends primarily on baseline values of absolute excretion of urea and osmotically active substances. CONCLUSION: A reverse relationship exists between absolute excretion of urea, osmotically active substances and the degree of SKF in response to protein load in CGN patients both in intact nitrogen-excreting function and uremia. It is suggested that urea may be involved in regulation of intraglomerular hemodynamics by means of effect on tubular-glomerular feedback mechanism.

[Effects of different variants of low-protein diet on progression of chronic renal failure and indices of nutritional status in predialysis stage]. / Vliianie razlichnykh rezhimov malobelkovoi diety na progressirovanie khronicheskoi pochechnoi nedostatochnosti u pokazateli sostoianiia pitaniia na dodializnom étape.

AIM: To investigate effects of different variants of low-protein diet (LPD) (standard and with soy bean protein isolates) on inhibition of chronic renal failure (CRF) progression and prevention of protein-energy insufficiency in predialysis patients. MATERIALS AND METHODS: 150 patients with CRF were divided into three groups 50 patients each. Group 1 patients were given combined LPD with addition of soy bean isolate (0.4 g of protein per 1 kg of recommended body mass a day with standard diet and 0.2 g/kg with protein isolate SUPRO 760). Group 2 patients were given standard LPD without additives (0.6 g/kg a day). Patients of group 3 received free diet. All the patients were normally supplied with energy (at least 30-35 kcal/day). In the course of 26 months, clinical, laboratory, anthropometric, expected and functional parameters were measured each 4 months. RESULTS: Progression of CRF inhibited in patients with restricted protein provision. LPD had no negative effect on laboratory indices. Soy bean isolate LPD was more effective in inhibition of the disease progression than the standard one. CONCLUSION: LPD can be used for a long time for inhibition of the progression of CRF provided energy requirements are met. LPD with food additives (soya bean protein isolates) hold perspective for correction of metabolic disorders.

[Changes in the filtration function of the kidneys during the treatment of chronic glomerulonephritis]. / Izmeneniia fil'tratsionnoi funktsii pochek pri lechenii khronicheskogo glomerulonefrita.

The implications of the treatment variant and chronic glomerulonephritis (CGN) characteristics in the changes of renal function were evaluated by 220 treatment courses for CGN aggravation. A number of statistical methods were employed. In CGN patients free of renal insufficiency glomerular filtration was either unaffected or recovered after transitory decline. In chronic failure further creatinine clearance diminution was observed, serum creatinine levels went up. Corticosteroid treatment was much safer for the kidneys than cytostatics. With increasing duration of CGN, functional affection of the kidney becomes more frequent irrespective of the treatment kind. The same is true for the number of exacerbation and hypertension which are also involved in renal functional decline.

[The morphofunctional parallels in arterial hypertension in patients with chronic glomerulonephritis]. / Morfofunktsional'nye paralleli pri arterial'noi gipertonii u bol'nykh khronicheskim glomerulonefritom.

A study was made of the structural rearrangement of renal tissues in intravital nephrobiopsy specimens and of the functioning of the renin-angiotensin-aldosterone system and kallikrein-synthetic function in patients with mesangioproliferative (MSPGN) and membranous proliferative glomerulonephritis (MPGN). The morphological changes were revealed. The patients with associated MSPGN and secondary hypertension (SH) mostly demonstrated emptying and hyalinosis of arteries, whereas those with associated MPGN and SH manifested for the most part the derangement of the tubulointerstitial structures. In patients with MPGN, the levels of total renin (TR) and inactive renin (IR) were significantly higher than in those suffering from MSPGN. This can be regarded as risk factor of earlier development of SH. In MPGN patients, the content of TR and IR as well as that of active renin (AR) did not depend on the clinical pattern of chronic glomerulonephritis. As compared to MSPGN patients with isolated urinary syndrome, those with associated MSPGN and SH had a higher AR level, which agreed well with systolic and mean arterial pressure. Apparently, the latter one is implicated in the mechanism of SH in MSPGN. In associated MPGN and SH, kallikreinuria was found to be lowest, which may be the consequence of tubulointerstitial lesions. Discoordination of the renin-angiotensin and kallikrein systems is likely to be one of the causes of earlier formation and severe course of SH in the morphological pattern under consideration.

[The morphofunctional parallels in arterial hypertension in patients with chronic glomerulonephritis]. / Morfofunktsional'nye paralleli pri arterial'noi gipertensii u bol'nykh khronicheskim glomerulonefritom.

The restructure of renal tissue in intravital nephric biopsy specimens, renin-angiotensin-aldosterone together with kallikrein synthetic functions were studied and compared in patients with mesangioproliferative and membranoproliferative glomerulonephritis (MsPGN and MPGN). The characteristics of the morphological changes were defined. In MsPGN with secondary hypertension (SH), nephronic wasting and hyalinosis of arteries were mostly detectable whereas MPGN with SH was primarily marked by the derangement of the tubulointerstitial structures. In MPGN, the levels of total and inactive renin (TR and IR) were significantly higher than in MsPGN. This can be regarded as risk factor of early development of SH. The content of TR and IR and in addition that of active renin (AR) in MRGN did not depend on the clinical form of chronic glomerulonephritis. As compared to MsPGN with an isolated urinary syndrome, in MsPGN with SH, AR was prevalent, while its level correlated well with systolic and the mean arterial pressure. AR may be implicated in the mechanism of SH in MsPGN. In MPGN with SH, kallikreinuria was found to be extremely low, which may be consequent to tubulointerstitial injuries. The discoordination of the renin-angiotensin and kallikrein system may be one of the causes of earlier formation and the grave course of SH in the morphological pattern under consideration.

[The participation of the kallikrein-kinin system in edema formation in glomerulonephritis]. / Uchastie kallikrein-kininovoi sistemy v formirovanii otekov pri glomerulonefrite.

Involvement of the kallikrein-kinin system in the pathogenesis of renal edemas may be mediated by increase of vascular permeability, proteinuria, diuresis and natriuresis. Proceeding from these points, in 27 patients with morphologically proved chronic glomerulonephritis and the nephrotic syndrome, the serum kallikrein activity and its 24-hour urinary excretion level were measured. According to their edematous syndrome severity, all the patients were divided into 2 groups: 1) 19 patients with moderate edemas; 2) 8 patients with severe ones. During the follow-up period, there were no essential changes in patients' body weights, and no significant differences between the groups in clearances and excreted fractions of sodium, potassium, chlorine, osmotically active substances, and in serum albumin and cholesterol levels, 24-hour protein losses and blood pressure. As compared to the healthy (n-20) in all the patients a substantial and statistically significant increase in kallikrein activity was revealed in serum and urine. Kallikreinemia and kallikreinuria were significantly higher in Group 2 than those in Group 1. In the total group of examinees a significant direct relationship was established between the urinary kallikrein activity and summary sodium and potassium excretion as well as between the serum kallikrein activity and chlorine clearance. A direct correlation between the serum kallikrein activity and proteinuria was also found. Thus, a role of the kallikrein-kinin system in development of glomerulonephritic edemas concurrent with the nephrotic syndrome is hetero-directional.(ABSTRACT TRUNCATED AT 250 WORDS)

[THe role of the kallikrein-kinin system in the origin of proteinuria in glomerulonephritis]. / Rol' kallikrein-kininovoi sistemy v proiskhozhdenii proteinurii pri glomerulonefrite.

The kallikrein-kinin system of the blood serum (prekallikrein and kallikrein) was studied in 68 patients with chronic glomerulonephritis with the purpose of determining the significance of this system in the origin of proteinuria, protein content in the morning portion of urine and 24-hour portion. Linear correlation analysis revealed a direct relation of the levels of kallikrein and prekallikrein in the blood serum the morning and 24 losses of protein in patients suffering of glomerulonephritis with an isolated urinary syndrome (18 patients), nephrotic (27 patients) and glomerulonephritis with arterial hypertension.

[The role of the kallikrein-kinin and renin-angiotensin-aldosterone systems in the development of hypertension in glomerulonephritis]. / Rol' kallikrein-kininovoi i renin-angiotenzin-al'dosteronovoi sistem v formirovanii gipertenzii pri glomerulonefrite.

A total of 74 patients with various clinicomorphological variants of glomerulonephritis (GN) were examined. Only a high activity of the enzyme kinase-1 that destroys kinins and the kallikrein inhibitors alpha 1-antitrypsin, alpha 2-macroglobulin is a contribution of the kallikrein-kinin system made to the general antihypertensive "armoury" of the body, as shown by the study. The correlation between the kallikrein activity and the active renin/total renin ratio predetermines that kallikrein may participate in endogenous plasma renin activation in GN patients. In this case, the vasoconstrictive effect of renin may limit the antihypertensive action of kallikrein and kinins by a feedback mechanism.

[Characteristics of the toxicological action of carbophos against a background of polychloropinene]. / Osobennosti toksicheskogo deistviia karbofosa na fone polikhlorpinena.

Tests conducted with rabbits brought evidence that carbophos priming per os (1/25DL50 for 45 days) reduces the oxyhemoglobin dissociation rate, increases the ascorbic acid concentration in the blood and brain, of copper in the blood, brain and kidneys. Priming with a mixture of carbophos and polychloropinene (in a summary dose of 1/25DL50) was attended by a decline in the oxyhemoglobin, rising a concentration of ascorbic acid in the blood, of manganese in the kidneys and iron in the muscles. Changes in the oxyhemoglobin dissociation rate and ascorbic acid concentration were more significant after introduction of a mixture of pesticides.