Cystatin C and cystatin SN as possible soluble tumor markers in malignant uveal melanoma.

Background: The aim of the study was to determine the concentration of endogenous cystatin C and cystatin SN, as potential tumor biomarkers, in the serum and biological fluids of the eye in both healthy controls and patients with uveal melanoma.

Patients And Methods: The concentration of both cystatins was determined in the intraocular fluid (IOF), tear fluid, and serum of patients with uveal melanoma and compared to baseline measurements in IOF, tears, serum, cerebral spinal fluid, saliva and urine of healthy controls.

Results: The concentration of cystatin C in all the biological matrices obtained from healthy controls significantly exceeded the concentration of cystatin SN and was independent of gender.

Effect of Liposome-Encapsulated Dextrazide on Local Regulation of Extracellular Matrix Metabolism in Liver and Lungs of Mice with during Chronic BCG-Induced Granulomatosis.

The liposomal form of isonicotinic acid hydrazide conjugate with oxidized dextran (liposomeencapsulated dextrazide, LEDZ) injected intraperitoneally for 3 months to BALB/c mice with chronic BCG-induced granulomatosis (6 month after infection) down-regulated activities of protease (MMP) and antiprotease (TIMP-1, TIMP-2, α2-macroglobulin) components of the regulation system, which indicates a drop of destructive and inflammatory potential of BCGinduced granulomatosis. The persistent enhanced hyaluronidase activity in the liver and its reduced (normalized to control level) activity in the lungs after administration of LEDZ indicates a greater hydrolysis of hyaluronan in the liver than in the lungs. LEDZ-induced changes in MMP/TIMP system in mouse liver and lungs are characterized with relative elevation of protease activity over that of antiprotease one.

Content of the Major Extracellular Matrix Components of the Liver and Lungs in Mice with Chronic BCG-Granulomatosis Treated with Liposome-Encapsulated Dextrazide.

Administration of the liposome-encapsulated dextrazide (LEDZ) to mice 6 months after infection with mycobacterium BCG vaccine for 3 months modulated metabolism of collagens and the intensity of fibrosis of internal organs. In the liver, we observed a redistribution of glycosaminoglycans towards sulfated forms, a decrease in the content of hyaluronan, a change in the ratio of hydroxyproline fractions indicating a decrease in fibrosis via two mechanisms: suppression of synthesis and increased degradation of collagens. In the lungs, administration of LEDZ did not affect the content of sulfated glycosaminoglycans, but significantly reduced the content of hyaluronan, stimulated degradation of collagen, and reduced its synthesis, but these processes were insufficient for significant reduction of fibrotic complications in the lungs.

[Age-related features of the relationship between the content of vascular endothelial growth factor and indicators of lipid metabolism and extracellular matrix metabolism in men in the European part of the Russian Arctic.].

The content of vascular endothelial growth factor-A (VEGF-A) in blood plasma and its relationship with lipid and extracellular matrix metabolism in working-aged men (19-69 years), living and working in the European part of the Arctic zone of the Russian Federation (Russian Arctic), were studied. No age dependence of the plasma VEGF-A content was found. The correlation analysis, performed in different age groups, revealed significant associations of VEGF-A level with lipid parameters (CS, LDL-C, Apo B, atherogenicity coefficient, Apo B /Apo A1 ratio) and extracellular matrix metabolism (blood TIMP-4, MMP-2, MMP-3, MMP-9, hyaluronan, total and peptide-bound hydroxyproline, glycosaminoglycans).

Peculiarities of Collagen Turnover in Aging BALB/c Mice.

Examination of collagen turnover in the liver, lungs, and spleen of BALB/c mice revealed the age-related differences in the levels of hydroxyproline and its fractions. The highest level of total hydroxyproline was observed in the lungs and spleen of young (2-month-old) mice. In the liver, this level attained maximum at the age of 6 months at the expense of elevation of protein-bound hydroxyproline relatively its level in 2-month-old mice.

Antifibrotics Effect of Liposome-Encapsulated Composition of Oxidized Dextran and Isonicotinic Acid Hydrazide in Mice with BCG-Induced Granulomatosis Depends on Administration Route.

We studied the response of the extracellular matrix of the lungs and liver in mice with BCGinduced granulomatosis (3 months) after inhalation and intraperitoneal administration of liposome-encapsulated dextrazide (LEDZ): a conjugate of oxidized dextran (40 kDa) and isonicotinic acid hydrazide (INH). LEDZ inhalation proved to be more effective in reducing fibrosis severity, both in the lungs and liver. However, the mechanisms of the antifibrotic effect were different: increased degradation and reduced collagen synthesis in the lungs and reduced collagen synthesis and collagen degradation in the liver.

Remodeling of the Extracellular Matrix of the Liver in Mice with BCG-Induced Granulomatosis after Administration of Liposome-Encapsulated Composition of Oxidized Dextran and Isonicotinic Acid Hydrazide.

Remodeling of the extracellular matrix of the liver in mice with BCG-induced granulomatosis after 2-month course of intraperitoneal injections of isonicotinic acid hydrazide, oxidized dextran conjugated with isonicotinic acid hydrazide, dextrazide, and its liposome-encapsulated form manifested in modification of the proteoglycan composition and hydroxyproline fractions associated with changes in hyaluronidase and MMP activities. The antifibrotic effect of dextrazide and its liposome-encapsulated form manifested in reduction of hydroxyproline fractions that reflected the process of collagen synthesis. Administration of isonicotinic acid hydrazide was followed by a decrease in hydroxyproline fractions reflecting collagen synthesis (antifibrotics effect) and degradation (profibrotic effect), which can be explained by its hepatotoxic activity.

Effect of Liposomal Delivery of Oxidized Dextran with Isonicotinic Acid Hydrazide on Component Profile of Pulmonary Extracellular Matrix in Mice with BCG-Induced Granulomatosis.

Intraperitoneal injections of isonicotinic acid hydrazide (INH), dextrazide (oxidized dextran+INH), or liposomes loaded with dextrazide (INH dose of 14 mg/kg) over 2 months to mice with BCG-induced granulomatosis started from postinfection day 90 induced qualitative and quantitative changes in composition of pulmonary extracellular matrix. Both dextrazide and its liposomal form decreased the levels of sulfated glycosaminoglycans and uronic acids. In contrast to INH, both preparations did not decrease the levels of total glycosaminoglycans, proteins, and galactose.

[Apolipoprotein A-I stimulates secretion of insulin and matrix metalloproteinases by islets of Langerhans].

The development of type 2 diabetes mellitus (DM2) is accompanied by disturbances in lipid metabolism. These include the increase in serum levels of atherogenic fractions of very low-density (VLDL) and low-density lipoproteins (LDL), total cholesterol, triglycerides and apo B. In contrast, the level of antiatherogenic high density lipoproteins (HDL) and the content of apolipoprotein A-I (apoA-I) decreased.

Changes in Activity of Matrix Metalloproteinases and Serum Concentrations of Proinsulin and C-Peptide Depending on the Compensation Stage of Type 2 Diabetes Mellitus.

In patients with type 2 diabetes mellitus, serum activities of MMP-2 and MMP-7 were substantially decreased in comparison with apparently healthy individuals. At the decompensation stage, along with the increased content of glucose and glycated hemoglobin, a pronounced (3-fold) increase in proinsulin concentration was observed. On the contrary, MMP activity and C-peptide concentration decreased at this stage.

[Interrelation between the melatonin level and indicators of aging and fibrosis in men in the European part of the Arctic zone of Russian Federation.].

The results of the correlation analysis between the metabolite melatonin - 6-sulfatoxymelatonin (6-SMT) in the urine and the indicators of aging, interstitial fibrosis, the system of antioxidant protection in men in the Arctic are presented. Negative correlation of medium strength between 6-SMT with calendar age, biological age and molecular marker of aging p16INK4a in leukocytes was noted. A relationship of 6-SMT to fibrosis indices was found.

Cystatin C as a Marker of Progressing Cardiovascular Events during Coronary Heart Disease.

The role of cystatin C, an inhibitor of cysteine proteases, as an alternative and potent predictor of acute cardiovascular events in coronary heart disease (CHD) patients was examined and compared to that of other markers of cardiorenal abnormalities. The patients with CHD demonstrated elevated serum cystatin C, especially in cases with serious risk of cardiovascular complications. In comparison with other indicators of cardiorenal dysfunction, cystatin C can be viewed as an alternative predictor of cardiovascular complications, although its sensitivity is inferior to that of high-sensitivity C-reactive protein and natriuretic peptide.

[Proinsulin as a diagnostic biochemical marker of decompensated diabetes mellitus type II.].

The proinsulin is one of indices reflecting functional activity of pancreas. Under insulin-independent diabetes ration proinsulin/insulin increases. The study was carried out to evaluate content of proinsulin and other biochemical indices of blood serum depending on stage of compensation of diabetes mellitus type II.

[Quality of life for men of different ages in the russian European North and its relationship with self-reported health and hormonal status].

Assessment of the quality of life for male inhabitants of the Russian European North demonstrated decreased indices of physical health component (the scale of role functioning determined by physical condition) and mental health component (the scales of social functioning and role functioning determined by emotional state and mental health) compared to the inhabitants of Siberia as a comparison group. Men aged up to 29 had the highest values at all scales. The values decreased with age.

Content of circulating extracellular DNA, plasma activities of matrix metalloproteinases, and ultrastructure of the myocardium in hypothyroid rats with hypercholesterolemia.

Free circulating extracellular DNA, plasma activities of matrix metalloproteinases in hypothyroid rats, and ultrastructural changes in the myocardium were studied under conditions of experimental hypercholesterolemia. For suppression of thyroid function, the animals received antithyroid drug mercazolyl under conditions of cholesterol diet. Hypercholesterolemia in hypothyroid rats (thyroxine concentration 2-fold below the normal) was paralleled by a pronounced increase of the concentration of free circulating extracellular DNA and total matrix metalloproteinases 2 and 7 activity.

Structural changes in the myocardium and serum lipid spectrum in experimental hypercholesterolemia and hypothyroidism.

We studied the peculiarities of lipid spectrum of the blood and structural reorganization of the myocardium in experimental hypercholesterolemia with and without hypothyroidism. It was found that alimentary hypercholesterolemia accompanied by elevated total cholesterol, LDL, HDL, and triglyceride concentrations led to a decrease in body weight, heart weight, number of cardiomyocytes in the heart and induced pronounced lytic changes in cardiomyocytes, circulation disorders (sludge syndrome, echinocytosis of erythrocytes, lymphostasis), diffuse fibrosis of the stroma, and appearance of foam cells among diffuse mononuclear infiltrate cells. The combination of hypercholesterolemia with hypothyroid status caused more pronounced changes in the lipid spectrum and atherogenic index and more pronounced lytic and necrobiotic changes in cardiomyocytes.

Activity of matrix metalloproteinases during antimycobacterial therapy in mice with simulated tuberculous inflammation.

Matrix metalloproteinases are shown to be involved in the pathogenesis of tuberculosis inflammation. In the early stages of BCG-granuloma formation in mouse liver and lungs, the serum levels of matrix metalloproteinases 2 and 7 increased by 4.5 times and remained unchanged while the pathology developed.

Effect of polysaccharides and human plasma lipoproteins on the secretion of cystatin C by peritoneal macrophages from normal and tumor bearing mice.

Intact peritoneal macrophages in vitro secreted the cysteine proteinase inhibitor cystatin C. Polysaccharides stimulated cystatin C secretion: lipopolysaccharide < carboxymethylated beta-D-glucan < sulfoethylated beta-D-glucan. Human plasma low-density- (LDL) and high-density lipoproteins (HDL) are still more potent inducers of cystatin C secretion by macrophages.

[Epidemiology of hemorrhagic fever with renal syndrome in the north Volga-Viatka region].

The results of the ecological and epidemiological study of hemorrhagic fever with the renal syndrome (HFRS) in the Kirov region for the period of 1987-2000 are presented. HFRS morbidity rate varied from 1.3 to 13.

[Epidemiology of leptospirosis in the Kirov region].

The dynamics of leptospirosis morbidity in the Kirov region for many years is presented. The wide spread of leptospirosis foci, both natural and formed as the result of human activities, in the region is shown. The main role in infecting humans with leptospires belonged to the latter foci in a number of districts in the region was established.

Detection of apolipoprotein A-I, B, and E immunoreactivity in the nuclei of various rat tissue cells.

Proteins with apolipoprotein A-I immunoreactivity were detected in the fraction of non-histone acidic proteins isolated from nuclei of various rat tissue cells. These proteins were detected in the brain, liver, kidney, lung, heart, skeletal muscle, testis, spleen, and bone marrow. In the same fraction from liver nuclei, proteins with apoB and apoE immunoreactivity were also detected.

Distribution of tocopherol and apolipoprotein A-I immunoreactivity in rat liver chromatin.

[125I]Labelled lipoproteins (HDL, LDL, and VLDL) are actively taken up by the rat liver. The uptake rate in nonparenchymal liver cells was significantly higher than that in hepatocytes. Analysis of the distribution of the labelled lipoproteins in liver subcellular structures showed the presence of these compounds in the nuclei.

Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder.

In winters 1990-1991 and 1991-1992 women with and without seasonal affective disorder, winter type, were treated by light at 2500 lux either in the morning (0800h-1000h) or afternoon (1600h-1800h). In winter before light treatment, melatonin levels in serum in daytime (1200h and 1600h) were higher in patients compared to controls (p < 0.05).