PubMed Health⌕ Search

Biomedical subjects

L V Kozlovskaia

Publications and source records attributed to L V Kozlovskaia.

At least 19 recordsLinked to original sources

[Urine excretion of a monocytic chemotaxic protein-1 and a transforming growth factor beta1 as an indicator of chronic glomerulonephritis progression].

AIM: To measure urine and renal tissue levels of profibrogenic mediators (monocytic chemotaxic protein-1-MCP-1 and transforming growth factor beta1 - TGF-b1) in patients with chronic glomerulonephritis (CGN); to specify significance of these mediators for assessment of inflammation and fibrosis in the kidney and as prognosis criteria. ELISA, immunohistochemical tests, morphometry were used to study urine excretion of MCP-1 and TGF-b1, expression of TGF-b1 in renal tissue, interstitial area, respectively, in 63 patients with active proteinuric CGN. RESULTS: Patients with active proteinuric forms of CGN have higher urine excretion of MCP-1 and TGF-b1 than healthy controls. Urine excretion of MCP-1 in patients with nephrotic syndrome was significantly higher than in patients with moderate urinary syndrome. The highest MCP-1 urine excretion was observed in patients with persistent renal failure. Urine excretion of TGF-b1 depended on the level of creatinemia being the highest in marked proteinuria and stable renal dysfunction. Intensive urine excretion of TGF-b1 occurred in CGN patients with expression of this cytokine in renal interstitium. This confirms its local-renal origin. A correlation was found between urine values of MCP-1, TGF-b1 and severity of tubulo-interstitial fibrosis (TIF). High informative value (sensitivity and specificity) of urine MCP-1 and TGF-b1 are for the first time shown as markers of interstitial fibrosis. They are also important for making prognosis of CGN. CONCLUSION: It is shown that MCP-1 and TGF-b1 are essential for remodeling of tubulointerstitium. The urinary parameters mark TIF and can be used as criteria of activity and prognosis of CGN.

Adolescent↗

[The role of smooth muscle alpha-actin in development of renal fibrosis in patients with chronic glomerulonephritis].

AIM: To estimate expression of smooth muscle alpha-actin (a-SMA) in renal glomeruli and interstitium of patients with chronic glomerulonephritis (CGN) for assessment of the disease progression and prognosis. MATERIAL AND METHODS: Expression of a-SMA in renal tissue was studied immunohistochemically, area of the interstitium and the degree of its interstitial inflammatory infiltration were investigated morphometrically in 45 biopsy specimens of renal tissue from patients with different morphological types of CGN and 7 specimens of normal renal tissue. RESULTS: a-SMA expression in the glomeruli was higher in patients with proliferative morphological forms of CGN [34.3% (26.1-40.6)] than in patients with nonproliferative nephritis forms [22.3% (18.5-22.3)], p < 0.001; it was the highest in patients with sclerotic alterations in the glomeruli [55.3% (37-61.8)], p < 0.01. The degree of a-SMA expression in renal interstitium of CGN patients correlated most closely with severity of tubulo-interstitial fibrosis (Rs = 0.08, p < 0.001). There was no significant correlation between glomerular a-SMA expression in renal biopsies and proteinuria, creatinine level in the serum of CGN patients, while a-SMA interstitial expression correlated both with severity of proteinuria (rs = 0.5, p < 0.05) and that of renal failure (rs = 0.7, p < 0.001). CONCLUSION: High expression of a-SMA in CGN occurs both in the glomeruli and interstitium of the kidney and evidences for activation of fibrogenesis but only interstitional expression can be considered as a morphological sign of CGN progression and as a factor of an unfavourable prognosis.

Actins↗

[An AA-amyloidosis course in patients with rheumatoid arthritis].

AIM: To characterize renal amyloidosis in patients with rheumatoid arthritis and stages of amyloid nephropathy. MATERIAL AND METHODS: The trial covered 30 patients (6 males and 24 females) with documented rheumatoid arthritis (RA) complicated with secondary AA-amyloidosis. Amyloidosis diagnosis was confirmed in all the patients morphologically, the samples were studied with the peroxidase immunohistochemical method using specific monoclonal antibodies to SAA. Clinical manifestations of RA were assessed by the disease activity, functional impairment of the joints, x-ray alterations, extraarticular signs of RA, etc. All the patients were examined clinically, total blood count and biochemical tests were made. RESULTS: In 23 (77%) of 30 examinees with RA, proteinuria as the first clinical symptom of AA-amyloidosis emerged with the first 15 years of RA. RA of the second-third degree of activity were diagnosed in 25 (83%) patients, 21 (70%) patients had apparent destructive changes in the joints (x-ray stage III-IV). Severe functional insufficiency of the joints was observed in 25 (83%) patients, deformation of the joints - in 27 (90%) patients. Clinically, renal amyloidosis was characterized by change of stages - from moderate proteinuria to nephrotic syndrome and renal failure. Prognosis of amyloid nephropathy in RA depends on duration of the proteinuric stage: if this stage is short (3 years maximum), the prognosis is worse than in its long duration. CONCLUSION: RA ranks first among causes of secondary AA-amyloidosis. Development of AA-amyloidosis in RA patients is most probable in the first 15 years of the course of the articular process. Amyloidosis is more frequent in patients with severe clinical manifestations of RA.

Adult↗

[Proteinuria-induced mechanisms of tubulointerstitial remodeling and possibilities of nephroprotection in glomerulonephritis].

The authors describe various mechanisms (including cellular and molecular ones) that mediate the realization of interstitial inflammation under the influence of proteinuria components. The paper covers epithelial cell transdifferentiation processes, the role of angiotensin II, transforming growth factor beta, nuclear transcription factor NFkB, chemokines, endothelial factors etc. The effects of drugs routinely used in nephrology at present (angiotensin converting enzyme inhibitors, statines etc.) are presented in a new way according to the modern conception of the mechanisms of proteinuria-induced renal interstitial tissue remodeling in glomerulonephritis. The authors consider administration of antichemokine agents, which influences chemokine/chemokine receptor system, to be a prospective independent immunotherapeutic direction in treatment, aimed at prevention of glomerulonephritis progression.

Animals↗

[HCV infection and mixed cryoglubulinemia].

The authors present literature data and the results of their own studies of mixed cryoglobulinemia (MC) caused by chronic HCV infection, discuss issues concerning pathogenesis of MC as well as MC-associated cryoglobulinemic vasculitis and malignant lymphoproliferation, consider questions of MC influence on the course and prognosis of chronic HCV infection and anti-viral therapy effectiveness. MC was found in 43% of 207 patients with chronic hepatitis type C (CH-C), examined by the researchers. 30% of patients with CH-C and MC displayed clinical signs of vasculitis. The study established the direct correlation between MC severity and the frequency and degree of main clinical manifestations. The results show that more severe clinical variants of cryoglobulinemic glomerulonephritis are associated with MC type II. B-cell lymphoma, monoclonal immunoglobulinopathy and a range of autoimmune syndromes were observed in MC patients. The liver involvement in patients with MC was characterized by a significantly higher sclerosis index compared to the group of patients not having MC while medium liver process activity index was equal in both groups, which suggests possible existence of special mechanisms and faster progress of phibrosis in patients with MC.

Biomarkers↗

[Vascular purpura in patients with chronic diffuse hepatic diseases].

The purpose of the study was to evaluate clinical significance of vascular purpura (VP) in diagnostics and establishing prognosis of chronic diffuse hepatic diseases (CDHD). The subjects were 660 patients with CDHD of viral and non-viral origin, who were under long hospital observation. 72 CDHD patients had cutaneous vasculitis. 11% of CDHD patients developed VP, which corresponded to the frequency of other cutaneous manifestations--minor hepatic signs (palmar erythema, spider-like blood vessels in the skin, xanthelasmas etc.) There was insignificant difference in the frequency of VP between the patients with type B and C hepatitis (9.6%), on the one part, and patients with non-viral hepatic diseases--primary sclerosing cholangitis, autoimmune hepatitis, and Wilson-Konovalov disease (14.2%). According to morphological data, 84.3% of CDHD patients with VP developed the latter or had a VP relapse at the cirrhotic stage (50%) or at the stage of forming hepatic cirrhosis (34.3%). Renal involvement, which was significantly more frequent in CDHD patients with VP vs. patients without VP (32% and 11.4%, respectively), may deteriorate the prognosis. The authors conclude that cutaneous vasculitits is a universal sign of viral and non-viral CDHD, which should be taken into consideration when diagnosing and establishing prognosis of these diseases. The fact that VP is revealed mainly at the cirrhotic stage suggests that an important role in its development is played by dysfunction of the liver, one of the main organs that clear antigen and immune complexes (including those of viral origin), appearing via the portal system or circulating in blood.

Cholangitis, Sclerosing↗

[Markers of thrombophilia in pulmonary fibrosis complicated by pulmonary hypertension].

AIM: To determine the role of enhanced blood coagulation in pathogenesis of pulmonary hypertension (PH) at an early stage of fibrosing alveolitis (FA). MATERIAL AND METHODS: Clinical, functional, roentgenological, coagulation and immunological examinations were performed in 17 patients with idiopathic FA (IFA), in 6 patients with exogenic allergic alveolitis (EAA), in 15 FA patients with diffuse diseases of the connective tissue (FA-DDCT). The diagnosis was verified with high resolution computed tomography (HRCT). Lesser circulation was assessed by Doppler echocardiography. Morphological impairment of the lungs was specified in all the patients using analysis of the bronchoalveolar lavage. In 9 FA patients the diagnosis was verified at thoracoscopic biopsy of the lung. The control group consisted of 16 healthy volunteers. Thrombin-antithrombin complex (TAT) and thrombocytic factor 4 (TF-4) were estimated with ELISA as stable, highly sensitive markers of thrombophilia. RESULTS: The TF-4 level was elevated in all IPD patients (p < 0.05), the elevation being highest in FA-DDCT (p < 0.007). With FA progression, TF-4 concentration went down. A weak negative correlation (p < 0.047, r = -0.38) was found with average pressure in the pulmonary artery (PAAP). TAT was higher than control in all the groups (p < 0.05). Maximal TAT values were registered in EAA. If HRCT detected active inflammation and in development of irreversible fibrous changes TAT was higher vs control. A direct correlation between TAT level and PAAP was not found. CONCLUSION: Disorders in thrombocytic and plasmic links of hemostasis are detectable early in IPD. Stable markers of thrombophilia (TAT and TF-4) reflect activity of inflammation in FA. They can be also used as sensitive diagnostic tests for diagnosis of PH and diagnosis of patients with activated coagulation system in IPD.

Adult↗

[Vascular purpura associated with chronic diffusive hepatic pathologies].

The study results related with the rate of vascular purpura in 660 patients with different-type chronic diffusive hepatic pathologies both of the viral and other natures are described in the paper. The main regularities characterizing the phenomenon (spread and possible cause of purpura development) are defined. According to an analysis of actual materials, dermal vasculitis is not an exclusive feature of virus-associated hepatitis or liver cirrhosis. Vascular purpura can be regarded, on the basis of the obtained data, as a universal sign typical of any liver pathologies.

Adolescent↗

[Role of endothelial dysfunction and coagulation disorders in the development of pulmonary fibrosis in patients with interstitial lung diseases].

Thirty-two patients with different forms of interstitial lung diseases (ILD), such as idiopathic fibrosing alveolitis (IFA) (n = 17) and fibrosing alveolitis concurrent with diffuse connective tissue diseases (FA-DCTD), were examined. Clinical, echocardiographic, computed tomographic, coagulative, and immunological studies were performed. Enzyme immunoassay was used to determine the levels of a complex of thrombin and antithrombin III (TAT) and platelet factor IV (PF-IV). There were significant increases in the levels of PF-IV (4.36 +/- 0.25 mg/l) and TAT (10.87 +/- 3.8 mg/l) in patients with ILD as compared to the control (2.75 +/- 0.47 and 1.8 +/- 0.2 mg/l, respectively; p < 0.05). In patients with early FA-DCTD with the predominance of the milk glass syndrome during high-resolution CT (HRCT), the level of PF-IV was greater than the normal levels (p < 0.05) and decreased with the progression of the disease and with the formation of the honeycomb lung. If there were HRCT signs of active inflammation, the level of TAT was higher than that in the control; this was also in the development of irreversible fibrous changes.

Blood Coagulation Disorders↗

[Early diagnosis of renal damage in hypertensive patients].

AIM: To determine early criteria of renal affection in hypertensive patients for improvement of diagnosis and treatment of hypertensive nephropathy. MATERIAL AND METHODS: 148 patients with essential hypertension (EH) were examined (82 males, 66 females, mean age 43.64 +/- 11.35 years). Of them, 46 patients (24 young males among them) had EH of new onset (NOH) and 102 patients had EH of long duration (LDEH). The examination included investigation of lipid, carbohydrate, uric acid metabolism, renal function, microalbuminuria, intrarenal hemodynamics (color dopplerography on ALOKA SSD-2000 MultiView. RESULTS: 50% of NOH and 90% of LDEH patients had metabolic disorders: excessive body weight, hypercholesterolemia, hypertriglyceridemia, uric acid disbolism, impaired glucose tolerance. These disorders, except uric acid metabolism, correlated in severity with duration and severity of EH. Intensity of microalbuminuria depends on EH duration, severity of concomitant metabolic defects. Markers of early renal damage in EH patients are increased intrarenal peripheral vascular resistance and microalbuminuria. These alterations are detectable in 30% NOH patients (at the disease onset). Treatment with ACE inhibitors eliminates microalbuminuria, diminished hyperfiltration and improved intrarenal circulation. This justifies use of ACE inhibitors for nephroprotection in EH patients. CONCLUSION: Monitoring of the above early markers of renal damage and metabolic shifts is essential for assessing progression of hypertensive nephropathy and control over efficacy of antihypertensive treatment including ACE inhibitors.

Adult↗

[Clinical implications of DNA-topoisomerases examination in renal biopsies from patients with nephritis].

AIM: To study expression of topoisomerases (TI) I and II alpha (DNA-bound enzymes involved in transcription and replication) in renal tissue as markers of activity and prognosis of glomerulonephritis (GN) decisive for choice of immunodepressive therapy. MATERIAL AND METHODS: TI expression was studied immunohistochemically in renal biopsies from 177 patients with different morphological variants of GN and in the samples of unaffected kidney tissue removed in 12 patients for local tumors. RESULTS: There are definite differences between proliferative and non-proliferative GN variants--elevation of TI levels and monocytic infiltration in proliferative GN. Focal-segmental glomerulosclerosis is characterized by a high TI II alpha level in mesangial cells and monocytic infiltration of the glomeruli which are typical for inflammation. A statistical relationship between TI levels in mesangial cells and glomerular epithelium suggests a pathogenetic relation between these links of the pathological process. Molecular markers of activation and proliferation of cells and direct inductors of the inflammatory process (cells of monocytic infiltrate) closely correlated with the activity index--an integral indicator of inflammatory activity, as well as with the integral indicator of sclerotic processes in renal tissue--sclerosis index. Monocytic infiltration in the interstitium correlated both with morphological manifestations of activity, progression of nephritis and their clinical equivalents. In high TI expression GN resistance to immunodepressive therapy rose. To overcome the resistance, immunodepressive therapy must be more active--large doses and duration of treatment. In patients with lupus nephritis and mesangiocapillary GN renal prognosis was worse in the presence of high TI expression in mesangial cells and epithelium of the renal canaliculi. CONCLUSION: The authors are the first to demonstrate TI expression in renal tissue of GN patients, correlation of its level with activity of renal process as well as its role in prediction of response to treatment and the rate of renal failure progression. It is suggested that high TI expression entails a progressive course of GN.

Biomarkers↗