338 research outputs found

    Эвакуация населения при чрезвычайных ситуациях

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    В результате аварии на Чернобыльской АЭС (1986 г.) радиационное загрязнение затронуло все страны Северного полушария. На опасно загрязненных территориях оказалось более 1 млн. чел. В ряду поколений число смертельных онкологических заболеваний может составить десятки тысяч человек.As a result of the Chernobyl accident (1986), all countries of the Northern Hemisphere were affected by radiation pollution. In dangerously contaminated areas was more than 1 million people. In a number of generations, the number of deadly cancer can amount to tens of thousands of people

    Differential patterns of PMN-elastase and type III procollagen peptide in knee joint effusions due to acute and chronic sports injuries

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    In 38 traumatic knee joint effusions the proteolytic enzyme PMN-elastase (PMN-E) and the repair marker procollagen III aminoterminal peptide (PIIINP) were determined. According to the period between trauma and first aspiration of the effusion, the patients were divided into 3 groups. Group I (17 patients; period between trauma and first aspiration not longer than 72 hours) showed high concentrations of PMN-E (up to 5400 ng/ml) and low concentrations of PIIINP (<13 U/ml). Group II (11 patients; aspiration within 4 to 14 days) had mean PMN-E and PIIINP concentrations of 125.6 ng/ml and 52.1 U/ ml, respectively. In group III (10 patients, aspiration after 14 days) mean PMN-E concentration was 123.8 ng/ml and mean PIIINP concentration was 63.4 U/ml. Graphic depiction of PMN-E and PIIINP levels in each individual sample as a function of time between trauma and fluid collection revealed highly increasing PMN-E levels during the first 24 posttraumatic hours, followed by rapidly decreasing levels within 72 hours post trauma, and no change after the 4th posttraumatic day. In contrast, PIIINP increased continuously up to the first posttraumatic week and stayed at high levels up to 90 days (end of the observation period). The differential patterns of PMN-E and PIIINP concentration in knee joint effusions may be useful in estimating the period between trauma and first treatment (aspiration of effusion) and should, therefore, be helpful in detecting degenerative lesions, which seem to be characterized by low PMN-E concomitantly with high PIIINP levels

    Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis

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    <p>Abstract</p> <p>Background</p> <p>Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of collagens by proteases produces small fragments, so-called neoepitopes, which are released systemically. Technologies investigating MMP-generated fragments of collagens may provide more useful information than traditional serological assays that crudely measure total protein. In the present study, we developed an ELISA for the quantification of a neoepitope generated by MMP degradation of type IV collagen and evaluated the association of this neoepitope with liver fibrosis in two animal models.</p> <p>Methods</p> <p>Type IV collagen was degraded <it>in vitro </it>by a variety of proteases. Mass spectrometric analysis revealed more than 200 different degradation fragments. A specific peptide sequence, 1438'GTPSVDHGFL'1447 (CO4-MMP), in the α1 chain of type IV collagen generated by MMP-9 was selected for ELISA development. ELISA was used to determine serum levels of the CO4-MMP neoepitope in two rat models of liver fibrosis: inhalation of carbon tetrachloride (CCl<sub>4</sub>) and bile duct ligation (BDL). The levels were correlated to histological findings using Sirius red staining.</p> <p>Results</p> <p>A technically robust assay was produced that is specific to the type IV degradation fragment, GTPSVDHGFL. CO4-MMP serum levels increased significantly in all BDL groups compared to baseline, with a maximum increase of 248% seen two weeks after BDL. There were no changes in CO4-MMP levels in sham-operated rats. In the CCl<sub>4 </sub>model, levels of CO4-MMP were significantly elevated at weeks 12, 16 and 20 compared to baseline levels, with a maximum increase of 88% after 20 weeks. CO4-MMP levels correlated to Sirius red staining results.</p> <p>Conclusion</p> <p>This ELISA is the first assay developed for assessment of proteolytic degraded type IV collagen, which, by enabling quantification of basement membrane degradation, could be relevant in investigating various fibrogenic pathologies. The CO4-MMP degradation fragment was highly associated with liver fibrosis in the two animal models studied.</p

    Recombinant Expression, Purification, and Functional Characterisation of Connective Tissue Growth Factor and Nephroblastoma-Overexpressed Protein

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    The CCN family of proteins, especially its prominent member, the Connective tissue growth factor (CTGF/CCN2) has been identified as a possible biomarker for the diagnosis of fibrotic diseases. As a downstream mediator of TGF-β1 signalling, it is involved in tissue scarring, stimulates interstitial deposition of extracellular matrix proteins, and promotes proliferation of several cell types. Another member of this family, the Nephroblastoma-Overexpressed protein (NOV/CCN3), has growth-inhibiting properties. First reports further suggest that these two CCN family members act opposite to each other in regulating extracellular matrix protein expression and reciprocally influence their own expression when over-expressed. We have established stable HEK and Flp-In-293 clones as productive sources for recombinant human CCN2/CTGF. In addition, we generated an adenoviral vector for recombinant expression of rat NOV and established protocols to purify large quantities of these CCN proteins. The identity of purified human CCN2/CTGF and rat CCN3/NOV was proven by In-gel digest followed by ESI-TOF/MS mass spectrometry. The biological activity of purified proteins was demonstrated using a Smad3-sensitive reporter gene and BrdU proliferation assay in permanent cell line EA•hy 926 cells. We further demonstrate for the first time that both recombinant CCN proteins are N-glycosylated

    Технологические решения для строительства разведочной вертикальной скважины глубиной 2420 метров на газовом месторождении (Тюменская область)

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    Технологические решения для строительства разведочной вертикальной скважины глубиной 2420 метров на газовом месторождении (Тюменская область).Technological solutions for the construction of a vertical exploration well with a depth of 2420 meters at the gas field (Tyumen region)

    Финансовая грамотность как фактор становления успешной личности

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    Финансовая грамотность на всех этапах развития и становления личности - необходимость современной России. В статье раскрывается примерное содержание рабочих программ для факультативов и дополнительных занятий по дисциплине "Основы финансовой грамотности" и опыт проведения семинара на тему финансовой грамотности

    Comparison of accuracy of fibrosis degree classifications by liver biopsy and non-invasive tests in chronic hepatitis C

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    <p>Abstract</p> <p>Background</p> <p>Non-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been thoroughly evaluated in comparison to liver biopsy, especially in clinical practice and for Fibroscan. Therefore, the main aim of the present study was to evaluate the accuracy of detailed fibrosis classifications available for non-invasive tests and liver biopsy. The secondary aim was to validate these accuracies in independent populations.</p> <p>Methods</p> <p>Four HCV populations provided 2,068 patients with liver biopsy, four different pathologist skill-levels and non-invasive tests. Results were expressed as percentages of correctly classified patients.</p> <p>Results</p> <p>In population #1 including 205 patients and comparing liver biopsy (reference: consensus reading by two experts) and blood tests, Metavir fibrosis (F<sub>M</sub>) stage accuracy was 64.4% in local pathologists vs. 82.2% (p < 10<sup>-3</sup>) in single expert pathologist. Significant discrepancy (≥ 2F<sub>M </sub>vs reference histological result) rates were: Fibrotest: 17.2%, FibroMeter<sup>2G</sup>: 5.6%, local pathologists: 4.9%, FibroMeter<sup>3G</sup>: 0.5%, expert pathologist: 0% (p < 10<sup>-3</sup>). In population #2 including 1,056 patients and comparing blood tests, the discrepancy scores, taking into account the error magnitude, of detailed fibrosis classification were significantly different between FibroMeter<sup>2G </sup>(0.30 ± 0.55) and FibroMeter<sup>3G </sup>(0.14 ± 0.37, p < 10<sup>-3</sup>) or Fibrotest (0.84 ± 0.80, p < 10<sup>-3</sup>). In population #3 (and #4) including 458 (359) patients and comparing blood tests and Fibroscan, accuracies of detailed fibrosis classification were, respectively: Fibrotest: 42.5% (33.5%), Fibroscan: 64.9% (50.7%), FibroMeter<sup>2G</sup>: 68.7% (68.2%), FibroMeter<sup>3G</sup>: 77.1% (83.4%), p < 10<sup>-3 </sup>(p < 10<sup>-3</sup>). Significant discrepancy (≥ 2 F<sub>M</sub>) rates were, respectively: Fibrotest: 21.3% (22.2%), Fibroscan: 12.9% (12.3%), FibroMeter<sup>2G</sup>: 5.7% (6.0%), FibroMeter<sup>3G</sup>: 0.9% (0.9%), p < 10<sup>-3 </sup>(p < 10<sup>-3</sup>).</p> <p>Conclusions</p> <p>The accuracy in detailed fibrosis classification of the best-performing blood test outperforms liver biopsy read by a local pathologist, i.e., in clinical practice; however, the classification precision is apparently lesser. This detailed classification accuracy is much lower than that of significant fibrosis with Fibroscan and even Fibrotest but higher with FibroMeter<sup>3G</sup>. FibroMeter classification accuracy was significantly higher than those of other non-invasive tests. Finally, for hepatitis C evaluation in clinical practice, fibrosis degree can be evaluated using an accurate blood test.</p

    PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

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    The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al
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