[Diagnostic value of urinary biomarkers excretion in estimation of morphological lesions in patients with primary glomerulopathies].

AIM: To investigate the diagnostic value of biomarkers in assessing the severity of sclerotic and atrophic lesions in primary glomerulopathies. MATERIALS AND METHODS: One hundred patients were included in the study, according to the results of kidney biopsy in 9 (9%) cases minimal change disease was diagnosed, in 28 (28%) focal segmental glomerulosclerosis, in 26 (26%) membranous nephropathy and in 37 (37%) IgA nephropathy. The clinical course of nephropathy was evaluated, standard laboratory tests were performed, and urinary excretions of cystatin C, 1-microglobulin, 2-microglobulin and NGAL were measured. The degree of glomerulosclerosis was assessed quantitatively, tubulointerstitial sclerosis and tubular atrophy semiquantitatively. RESULTS: According to the results of linear correlations and ROC-analysis, urinary excretion of cystatin C and 1-microglobulin had diagnostic value for early degree of tubulointerstitial sclerosis (cut-off value 319.9 and 10.94 mg/day, respectively). Urinary excretion of 2-microglobulin reflected the initial degree of tubalar atrophy (cut-off value of 0.224 mcg/day), as well as tubulointerstitial sclerosis of various degrees of severity (cut-off value 0.224 and 0.240 mkg/day). NGAL urinary excretion was the only marker of early degree of glomerulosclerosis with its excretion of more than 1445.4 ng/day and tubular atrophy, with a severity of 50% or more (cut-off value 4897.8 ng/day). CONCLUSION: A comprehensive assessment of sclerotic and atrophic lesions in the renal parenchyma, can be performed using a panel of traditional (GFR, proteinuria) and specific biomarkers (1-, 2-microglobulins, cystatin C, NGAL) to implement a comprehensive, personalized approach, as well as to assess the prognosis of nephropathy. In addition, the evaluation of the panel of different biomarkers can be used in those clinical situations where kidney biopsy can not be performed.

[Epicardial and subcutenious adipose tissue adiponectin gene expression in coronary artery disease patients].

Aim To determine the expression of adiponectin gene (ADIPOQ) and the content of high-molecular-weight adiponectin (HMWA) in epicardial (EAT) and subcutaneous adipose tissue (SCAT) in patients with ischemic heart disease (IHD).Material and methods Paired samples of EAT and SCAT and blood serum were withdrawn from patients with IHD after bypass surgery and 16 subjects without IHD (comparison group). Matrix RNA (mRNA) level was measured using real-time polymerase chain reaction. HMWA levels in EAT and SCAT were evaluated by Western blotting. Serum adiponectin concentration was measured immunoenzymatically. For all patients, echocardiography was performed to measure the EAT thickness; coronarography was performed to determine severity of coronary atherosclerosis.Results Serum adiponectin concentration was lower in IHD patients than in the comparison group (p<0.001). Levels of ADIPOO gene mRNA and HMWA in SCAT were lower in IHD patients than in the comparison group (р=0.020 and p=0.003, respectively). The HMWA level in EAT was lower with the EAT thickness of 8 mm compared to the HMWA level in IHD patients with EAT ≤8 mm (p=0.034).Conclusion The decreased serum concentration of antiatherogenic adiponectin and the reduced expression of ADIPOQ gene in SCAT (mRNA, HMWA) are associated with IHD.

Serum uromodulin as an early biomarker of tubular atrophy and interstitial fibrosis in patients with glomerulopathies.

AIM: To assess the significance of the serum uromodulin (Tamm-Horsfall protein - THP) concentration (Sumo) as an early biomarker of tubular atrophy (TA) and interstitial renal fibrosis (IF) in patients with glomerulopathies. MATERIALS AND METHODS: 84 patients with glomerulopathy and 11 practically healthy persons (control) were examined. Uromodulin concentrations in serum and urine (Uumo) were measured, renal excretion of this protein and the estimated glomerular filtration rate (eGFR) were established. A semi-quantitative assessment of nephrobioptates was performed. RESULTS: Sumo decreases with a minimum expression of tubular atrophy (TA) or interstitial fibrosis (IF), when the values of eGFR still remain normal. Variations of such excretory parameters of THP as Uumo, daily excretion, and ratio: urinary uromodulin / urinary creatinine, did not manifest a similar trend. CONCLUSION: Sumo is promising as an early biomarker of fibrotic and atrophic renal damage. The parameters of renal excretion of THP do not seem to have this property. The reason for the delay in the decline of Uumo in the progression of CKD as compared to the decrease in Sumo seems to be the need to maintain a sufficient Uumo to counteract urinary tract infection and stone formation.

[Acute kidney injury and tubular biomarkers after hematopoietic stem cell transplantation].

AIM: To determine the value of molecular biomarkers (BMs) associated with tubular epithelial damage in developing and predicting acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT). SUBJECTS AND METHODS: The open-label observational prospective study enrolled 90 patients (46 males and 44 females) who had undergone HSCT. The concentrations of BMs (calbindin, clusterin, interleukin-18 (IL-18), kidney injury molecules-1 (KIM-1), glutathione S-transferase-π (GST-π), and monocyte chemoattractant protein-1 (MCP-1) were measured in urinary samples 7 days before HSCT (week 0) and at weeks 1, 2, 3, 4, and 5. Main clinical parameters were simultaneously monitored. AKI was diagnosed and stratified according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. RESULTS: At weeks 1, 2, 3, 4, and 5 after HSCT, the proportion of AKI cases was 7.8, 8.9, 12.5, 27.3, and 35.9%, respectively. The elevated urinary levels of BMs (above the median) were found to be substantially more common than AKI cases. The urinary excretion of the majority of BMs dramatically increased in the early HSCT period. The median number of simultaneously elevated BMs was 3 (2; 5) during the entire follow-up period. Clusterin, MCP-1 and KIM-1 positively and significantly correlated with serum creatinine at the week following the determination of BMs in the multivariate linear regression models adjusted for other confounders. The higher urinary KIM-1 and/or MCP-1 excretion regardless of other clinical indicators was associated with the higher relative risk (RR) of AKI, which increased by 2.3 times with a rise in one of these indicators and by 3.4 times with a rise in both indicators. CONCLUSION: Multiple renal toxic effects after HSCT result in a substantial and simultaneous elevation of urinary excretion of BMs for tubular damage. Among the BMs studied, KIM-1 and MCP-1 seem to be the most suitable molecules for assessing the risk of AKI in this cohort of patient within the predictive diagnostic approach.

[Study of osteoprotective and hypolipidemic effects of estrogen 8α-analogues].

The aim of this work was to study the ability of some estrogen 8α-analogues, that have CH3-group in the C-3 position, exhibit osteoprotective and cholesterolemic effects. The properties of these analogues was comparisoned with effects of native estradiol and 17α-ethynylestradiol (EE). We showed that compounds 3 ((d,l)-17ß-acethoxy-3-methoxy-8α-estra-1,3,5(10)-triene) and 4 ((d,l)-3-methoxy-8α-estra-1,3,5(10)-triene-17-one) had the same osteoprotective and cholesterolemic effects as EE. The utherotropic effects of compound 3 and EE were the same, while the utherotropic activity of 17-keto derivative (compound 4) was higher than effect of EE. The osteoprotective and cholesterolemic effects of compounds 5 and 6 (d- or l-17ß-acethoxy-3-methoxy-13-ethyl-8α-gone-1,3,5(10)-triene) were approximately the same, however the utherotropic action of these compounds was different: the compound 5 had significantly lower activity, but the compound 6 had the same effect in comparison with EE. Thus, all studied estrogen 8α-analogues may be used as basic constructions for structural modifications which is necessary as medications with while spectrum of biological properties.

[The indices dynamics of platelet pool and the level of TGF-beta1 in different forms of acute pancreatitis].

The results of study of quantitative functional characteristics of platelets are shown in patients with acute pancreatitis. The patients (57 people) with acute pancreatitis were examined: 40 patients had a mild clinical course of acute pancreatitis and 40 patients had a severe clinical course of acute pancreatitis. The circular functional mass of platelets and the level of TGF-beta1 were determined in dynamics in patients with acute destructive pancreatitis. A correlated analysis was made among the results obtained by means of laboratory and instrumental examinations and clinical course of acute pancreatitis. It was found, that the increase of TGF-beta1 and circular functional mass of platelets in the course of several days was really a good prognostic factor of clinical course of acute pancreatitis. The data obtained showed that the changes of indices of quantitative and functional characteristics of platelets are the important pathogenetic criterion of prognosis for severity of clinical course of acute pancreatitis.

[Diagnostic value of cystatin C and neutrophil gelatinase-associated lipocalin in primary glomerulopathies].

AIM: To study an association between clinical and morphological evidence and the serum and daily urinary levels of cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) in patients with primary glomerulopathies. SUBJECTS AND METHODS: The investigation included 104 patients; morphological examination showed minimal change disease in 15 (14.4%) patients, focal segmental glomerulosclerosis in 24 (23.1%), membrane nephropathy in 32 (30.8%), and IgA nephropathy (mesangioproliferative glomerulonephritis) in 33 (31.7%). The investigators analyzed the clinical type of nephropathy, performed conventional laboratory and instrumental examinations, and determined the level of CysC (by immunoturbodimetry) and NGAL (by enzyme immunoassay) in the serum and daily urine taken before kidney biopsy. The degree of glomerulosclerosis, tubulointerstititial sclerosis, and tubular atrophy was semiquantitatively estimated. RESULTS: Urinary CysC and NGAL excretion correlated with the degree of glomerulosclerosis and proteinuria and the reduced glomerular filtration rate (GFR) regardless of the method of its determination. The urinary level of NGAL positively correlated with the degree of tubular atrophy. The GFR value determined from serum CysC and creatinine levels more precisely reflected the degree of glomerulosclerosis. CONCLUSION: The tubulointerstitial compartment in primary glomerulopathies should be determined not only by morphological changes, but also by tubular function parameters by estimating the urinary excretion of biomarkers. The urinary content of CysC reflects tubular epithelial dysfunction whereas that of NGAL also characterizes tubular atrophy. To estimate the degree of glomerulosclerosis, it is more preferable to use the GFR calculated from the blood concentrations of CysC and creatinine, by keeping in mind clinical findings (using Chronic Kidney Disease Epidemiology Collaboration formula, 2012).

[Correlations between the levels of vitamin D, parathormone, calcium, blood phosphates in patients with chronic kidney disease not treated with kidney replacement therapy].

AIM: To characterize correlations between the levels of vitamin D, parathormone, calcium, blood phosphates in patients with different stages of chronic disease of the kidney (CDK) given no therapy replacing renal function (TRRF). MATERIAL AND METHODS: Serum levels of creatinine, electrolytes, parathormone (PTH), 25(OH)-vitamin D (calcidiol-CD), 1,25 (OH)2-vitamin D (calcitriol-CT), calcium (Ca) and phosphates (P) excretion with urine were studied in 465 patients aged 52.2 +/- 15.5 years with CDK stage I-V given no TRRF having mean glomerular filtration rate (GFR) 51.8 +/- 27.1 ml/min. RESULTS: A CT level lowered with CDK progression and directly correlated with GFR, blood levels of Ca and CD. Correlation with PTH was not found. CD did not correlate with GFR. PTH rose from stage II CDK and its concentration in the blood correlated negatively with GFR, blood Ca (in lesser degree), directly correlated with P. Ca lowered at stage V of CDK, P--at stage II, increased at stage IV. In reduction of GFR 24-h excretions of P and Ca diminished in spite of growth of their excreted fractions and were related directly with CT. CONCLUSION: A rise of PTH and fall of CT occur at early CDK stages. P disbolism seems to play a key role in genesis of hyperparathyrosis. We are the first to show lowering of 24-hour Ca and P excretion with CDK progression which may be caused by a progressive CT deficiency.

[The significance of investigation of the endothelium function in diagnosis and assessment of effectiveness of treatment of infective endocarditis].

The complex state of the endothelium function was studied in 25 patients with infective endocarditis in the preoperative and early terms after surgery. A reliable elevation of all indices of endothelium dysfunction independent of the localization of the formed heart disease was detected. Against the background of operative treatment reliable changes demonstrating an improved functional state of the endothelium were noted in the early postoperative period.

[Prevalence of subnormal glomerular filtration rate in patients with diabetes mellitus].

AIM: To evaluate prevalence of subnormal glomerular filtration rate (GFR) in diabetes mellitus (DM) patients with reference to albuminuria level. MATERIAL AND METHODS: GFR by MDRD and urine excretion of protein/albumin were estimated in 851 diabetic patients (473 with type 1 DM and 378 with type 2 DM). RESULTS: Normoalbuminuria (NAU), microalbuminuria (MAU) and proteinuria were detected in 54, 16 and 30% type 1 diabetics, respectively; 77% had subnormal GFR, in NAU 8.3% had GFR decline (< 60 ml/min) corresponding to stage III-IV chronic disease of the kidneys. In MAU the latter was present in 16.4%, in proteinuria--in 62.8%. Type 2 diabetics had NAU in 33.6% cases, MAU--in 17.7%, proteinuria--in 48.7%. Subnormal GFR < 60 ml/min was found in 40% cases with NAU and MAU. Most patients with proteinuria had chronic disease of the kidneys of stage III-V In a normal creatinine concentration in blood serum subnormal GFR < 60 ml/min was observed in type 1 DM in 7.6, in type 2 DM--in 33% cases. CONCLUSION: Prevalence of subnormal GFR in diabetic patients with NAU and MAU is rather high. This necessitates wide introduction of this index in screening, follow-up and classification of renal damage severity in DM as well as estimation of albuminuria/proteinuria.

[Lipid peroxidation in rabbit and rat visual system structures]. / Perekisnoe okislenie lipidov v strukturakh zritel'nogo trakta krolika i krysy.

In our work, the lipid peroxidation (LPO) in the retina, optic chiasma, and visual cortex of rat and rabbit brain was investigated. The contents of the LPO products (diene conjugates, triene conjugates, TBA-reactive products, Schiff bases) and oxidation index (calculated as 232/2 15) were similar in the retina and visual brain cortex of rats. In vivo, lipid oxidation in the optic chiasma was higher as compared with two other parts of visual tract. The similar data were obtained in our experiments with rabbit's visual tract. The sensitivity of tissues to peroxidation in vitro was studied in homogenates incubated with 0.2 mM ascorbate and 10 mkM FeSO4 for 20 min at 37 degrees C. The results of these experiments deviated from the data obtained in vivo, namely: the LPO in optic chiasma was lower than in the retina and the brain cortex. This data are in compliance with lipid composition of investigated parts of the visual tract of both animals. In our opinion, the high level of LPO in optic chiasma demonstrated in vivo is due to low antioxidants level in this part of the visual tract. Our findings also indicate that LPO in retina both in vivo and in vitro experiments are similar to those in the brain cortex and may be attributed to similar lipid composition and activity of antioxidant enzymes (such as superoxiddismutasa and glutathionereductase).

[Informative value of immunologic analysis of blood and ejaculate in diagnosing chronic prostatitis]. / Informativnost' immunologicheskogo analiza krovi i éiakuliata v diagnostike khronicheskogo prostatita.

Ejaculate and blood serum from 40 patients with chronic prostatitis were studied immunologically, IgG, IgA, sIgA, IgM concentrations in ejaculate may be greatly influenced by multicomponent composition of ejaculate. This means that it is impossible to diagnose chronic prostatitis only by changes of immunoglobulin concentrations in ejaculate. Data on IgA, sIgA concentrations plus on leukocyte count in ejaculate give more information for precise diagnosis of chronic prostatitis.

[Diagnostic role of interleukin-8 determination in chronic prostatitis]. / Diagnosticheskaia rol' opredeleniia interleikina-8 pri khronicheskom prostatite.

Measurements were made of interleukine-8 (IL-8) levels in ejaculate, prostatic secretion, blood serum of 60 patients with latent chronic prostatitis (CP). These levels were higher in CP patients than in healthy subjects. A rise in concentrations of IL-8 in prostatic secretion and ejaculate correlates with other inflammation markers. This may indicate the degree of CP activity. No relationship between IL-8 levels in ejaculate and prostatic secretion, and large dispersion of this marker allow using this criterion for diagnosis in combination with other indices of local immunity.

[Efficiency of the use of locomotive cab heating systems]. / Effektivnost' ispol'zovaniia sistem otopleniia kabin lokomotivov.

The paper describes the efficiency of the heating, thermal insulating, and air-tightness systems in the cabs of a railway rolling stock.

[The effect of rudotel on the synaptic activity of dopaminergic neurons]. / Vliianie rudotelia na sinapticheskuiu aktivnost' dofaminergicheskikh neironov.

The work discusses the neurochemical correlates of rat brain dopamin-synaptic activity after injection of 0.5 mg/kg rudotel (medazepam) as compared with intact animals. The parameters of functioning of D2-receptors in [3H]-dopamine binding, the content of catecholamines and their metabolites (high-performance liquid chromatography with electrochemical detection) were studied in the dopaminergic system in different brain areas (the striatum, frontal cortex, amygdala, hippocampus, hypothalamus, and accumbence).

Regional brain patterns of dopamine, metabolites and D2 receptors in memory.

Patterns of dopamine (DA), 3,4-dihydroxyphenyl acetic (DOPAC), and homovanillic (HVA) acids, para-tyramine (p-TA), and D2 receptors for eleven structures of forebrain and midbrain were examined at 1 and 6 days after one trial passive avoidance training of rats, at 1 day after "psychogenic" amnesia production, immediately following training, and at the last day after foot shock of rats with previous "psychogenic" amnesia administration. Essential dopaminergic differences have been found between the groups studied. More significant neurochemical changes were observed in rats from trained and retrieval training groups. Regional DA changes were accompanied by a diminution of DA metabolism, an increase of D2 receptor density and p-TA. These neurochemical alterations differentially characterized the regional neurochemical patterns found in rat's exhibition nonretention (trained), forgetting, and amnesia. It is suggested that the present data reflect the existence of quantitative relationships between D2 receptors, DA, and p-TA, which are probably important in modulation of memory.

[The molecular basis of dopamine synapse activity in the mechanisms of learning and amnesia]. / Molekuliarnaia osnova aktivnosti dofaminovogo sinapsa v mekhanizmakh obucheniia i amnezii.

Neurochemical events underlying the activity of the dopamine synapse during the retrieval of memory and its impairment ("psychogenic" amnesia) are considered in the paper. Physico-chemical parameters of operation of D2 receptor and catechole content were investigated in various brain areas (striatum, neostriatum, hypothalamus, amygdala, frontal cortex, hippocampus, nuclei accumbens, A9, and A10) in intact, learned, and amnestic rats. The impairment in the memory trace retrieval was found to be associated with a significant decrease in activation of synaptic dopamine receptors and a modification of the dopamine transformation pathway.

[Forgetfulness and amnesia: receptor mechanisms and brain mapping]. / Zabyvanie i amneziia: retseptornye mekhanizmy i kartirovanie mozga.

Inability to remember and amnesia have been shown to be active neurochemical processes. The coupled processes (blockade of the triggering DA stimulating system and activation of the inhibitory GABA-ergic system with the predominant value of postsynaptic D-2 receptors) are a neurochemical basis for development of amnesia. The mechanisms of spontaneous forgetting is provided by a decrease in the activity of the dopaminergic system along with the enhancement of benzodiazepine-GABA-ergic interferentional inhibition. The observed changes in dopamine metabolism, para-tyramine appearance, as well as restructure of D-2 receptors provide the activity of dopamine increasing mechanism which determines the retention of memory traces. A computer model of the spatial interaction of the dopamine membrane-receptor complex was constructed by scanning the samples of synaptic membranes after learning and amnesia. A new method of inducing psychogenic amnesia in human beings has been elaborated. Amnesia is characterized by the absence of increases in the number of cortical connections reflecting the emotional factor of information.

[Level of serotonin and 5-hydroxyindoleacetic acid in the brain and immunocompetent organs after immunization]. / Uroven' serotonina i 5-oksiindoluksusnoi kisloty v mozge i immunokompetentnykh organakh posle immunizatsii.

Twenty minutes after immunization the activation of the serotoninergic system was observed. High level of serotonin metabolism was retained for 24 h after immunization. Change of serotonin level in immunocompetent organs and adrenals took place later than in the brain.

[Changes in the level of dopamine and its metabolites in brain structures and immunocompetent organs in the formation of immune response]. / Izmenenie urovnia dopamina i ego metabolitov v strukturakh mozga i immunokompetentnykh organakh pri formirovanii immunnogo otveta.

By the method of liquid chromatography with electrochemical detection dopamine level increase was shown within 2 min after immunization of rats with sheep red blood cells in n. caudatus. In 20 min after the immune response the acceleration of dopamine metabolism was observed in nuclei A9, A10, A11, accumbens, in amygdala, hypothalamus and hippocampus. In immunocompetent organs dopamine level was changed in 24 h after the immunization.