52 research outputs found

    The regulatory role of cystatin C in autophagy and neurodegeneration

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    Autophagy is a dynamic cellular process involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. It is particularly important in neurons, which do not have a proliferative option for cellular repair. Autophagy has been shown to be suppressed in the striatum of a transgenic mouse model of Parkinson’s disease. Cystatin C is one of the potent regulators of autophagy. Changes in the expression and secretion of cystatin C in the brain have been shown in amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s diseases, and in some animal models of neurodegeneration, thus proving a protective function of cystatin C. It has been suggested that cystatin C plays the primary role in amyloidogenesis and shows promise as a therapeutic agent for neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases). Cystatin C colocalizes with the amyloid β-protein in the brain during Alzheimer’s disease. Controlled expression of a cystatin C peptide has been proposed as a new approach to therapy for Alzheimer’s disease. In Parkinson’s disease, serum cystatin C levels can predict disease severity and cognitive dysfunction, although the exact involvement of cystatin C remains unclear. The aim: to study the role of cystatin C in neurodegeneration and evaluate the results in relation to the mechanism of autophagy. In our study on humans, a higher concentration of cystatin C was noted in cerebrospinal fluid than in serum; much lower concentrations were observed in other biological fluids (intraocular fluid, bile, and sweat). In elderly persons (61–80 years old compared to practically healthy people at 40–60 years of age), we revealed increased cystatin C levels both in serum and intraocular fluid. In an experiment on C57Bl/6J mice, cystatin C concentration was significantly higher in brain tissue than in the liver and spleen: an indication of an important function of this cysteine protease inhibitor in the brain. Using a transgenic mouse model of Parkinson’s disease (5 months old), we demonstrated a significant increase in osmotic susceptibility of brain lysosomes, depending on autophagy, while in a murine model of Alzheimer’s disease, this parameter did not differ from that in the appropriate control

    Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development

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    Objectives. To investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development. Background. The increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population). Search for new biological markers is important for diagnosis and prognosis in eye tumors. Cystatin C, an endogenous inhibitor of cysteine proteases, plays an important protective role in several tumors. Lactoferrin was shown to express anti-tumor and antiviral activities. It was hypothesized that cystatin C and lactoferrin could serve as possible biomarkers in the diagnosis of malignant and benign eye tumors. Study design. A total of 54 patients with choroidal melanoma and benign eye tumors were examined (part of them undergoing surgical treatment). Serum, tear fluid and intraocular fluid samples obtained from the anterior chamber of eyes in patients with choroidal melanoma were studied. Methods. Cystatin C concentration in serum and eye biological fluids was measured by commercial ELISA kits for human (BioVendor, Czechia); lactoferrin concentration – by Lactoferrin-strip D 4106 ELISA test systems (Vector-BEST, Novosibirsk Region, Russia). Results. Cystatin C concentration in serum of healthy persons was significantly higher as compared to tear and intraocular fluids. In patients with choroidal melanoma, increased cystatin C concentration was similar in tear fluid of both the eyes. Lactoferrin level in tear fluid of healthy persons was significantly higher than its serum level. Significantly increased lactoferrin concentration in tear fluid was noted in patients with benign and malignant eye tumors. Conclusion. Increased level of cystatin C in tear fluid seems to be a possible diagnostic factor in the eye tumors studied. However, it does not allow us to differentiate between malignant and benign eye tumors. Similar changes were noted for lactoferrin in tear fluid

    The Fluorescent Probing Method in the Estimation of the Functional Probabilities of the Blood Plasma Transport Systems

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    During this work method of fluorescent probes with differently charged fluorescent dyes was used for estimation of binding ability of the blood plasma main transport proteins. Investigations were done at the patients with liver cirrhosis for creating on those basis fluorescent tests adapted for clinical use. Such tests should use for depending of severity degree of pathological process and for the correct choice of the most effective haemosorbent for extracorporeal blood purification in the definite clinical situation. Regularity was shown for the changes in the binding ability of the blood plasma main transport proteins in liver cirrhosis, which depended on the stage of the disease and allowed efficiently estimate severity degree of pathological process. Comparative evaluation of the efficacy of different charcoal haemosorbents widely used in clinical practice as well as "Prometheus" device was done in terms of endogenous intoxication syndrome correction at liver cirrhosis patients using results of biochemical analysis and method of fluorescent dyes. It was shown that the most effective sorbents were sorbents of "Prometheus" and between charcoal heamosorbents - "Carbocol"

    The Fluorescent Probing Method in the Estimation of the Functional Probabilities of the Blood Plasma Transport Systems

    No full text
    During this work method of fluorescent probes with differently charged fluorescent dyes was used for estimation of binding ability of the blood plasma main transport proteins. Investigations were done at the patients with liver cirrhosis for creating on those basis fluorescent tests adapted for clinical use. Such tests should use for depending of severity degree of pathological process and for the correct choice of the most effective haemosorbent for extracorporeal blood purification in the definite clinical situation. Regularity was shown for the changes in the binding ability of the blood plasma main transport proteins in liver cirrhosis, which depended on the stage of the disease and allowed efficiently estimate severity degree of pathological process. Comparative evaluation of the efficacy of different charcoal haemosorbents widely used in clinical practice as well as "Prometheus" device was done in terms of endogenous intoxication syndrome correction at liver cirrhosis patients using results of biochemical analysis and method of fluorescent dyes. It was shown that the most effective sorbents were sorbents of "Prometheus" and between charcoal heamosorbents - "Carbocol"

    10 Jahre elektronisches Portal "German Medical Science" für die medizinischen Wissenschaften

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    Das elektronische Portal "German Medical Science" wurde am 06. 12. 2003 in einer gemeinsamen Sitzung der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF), der Deutschen Zentralbibliothek für Medizin (ZB MED) und dem Deutschen Institut für Medizinische Dokumentation und Information (DIMDI) in Köln gegründet
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