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Sample records for normal fibrinolytic activity

  1. Activity assessment of microbial fibrinolytic enzymes.

    Science.gov (United States)

    Kotb, Essam

    2013-08-01

    Conversion of fibrinogen to fibrin inside blood vessels results in thrombosis, leading to myocardial infarction and other cardiovascular diseases. In general, there are four therapy options: surgical operation, intake of antiplatelets, anticoagulants, or fibrinolytic enzymes. Microbial fibrinolytic enzymes have attracted much more attention than typical thrombolytic agents because of the expensive prices and the side effects of the latter. The fibrinolytic enzymes were successively discovered from different microorganisms, the most important among which is the genus Bacillus. Microbial fibrinolytic enzymes, especially those from food-grade microorganisms, have the potential to be developed as functional food additives and drugs to prevent or cure thrombosis and other related diseases. There are several assay methods for these enzymes; this may due to the insolubility of substrate, fibrin. Existing assay methods can be divided into three major groups. The first group consists of assay of fibrinolytic activity with natural proteins as substrates, e.g., fibrin plate methods. The second and third groups of assays are suitable for kinetic studies and are based on the determination of hydrolysis of synthetic peptide esters. This review will deal primarily with the microorganisms that have been reported in literature to produce fibrinolytic enzymes and the first review discussing the methods used to assay the fibrinolytic activity.

  2. Improvement of Fibrinolytic Activity of Bacillus subtilis 168 by Integration of a Fibrinolytic Gene into the Chromosome.

    Science.gov (United States)

    Jeong, Seon-Ju; Park, Ji Yeong; Lee, Jae Yong; Lee, Kang Wook; Cho, Kye Man; Kim, Gyoung Min; Shin, Jung-Hye; Kim, Jong-Sang; Kim, Jeong Hwan

    2015-11-01

    Fibrinolytic enzyme genes (aprE2, aprE176, and aprE179) were introduced into the Bacillus subtilis 168 chromosome without any antibiotic resistance gene. An integration vector, pDG1662, was used to deliver the genes into the amyE site of B. subtilis 168. Integrants, SJ3-5nc, SJ176nc, and SJ179nc, were obtained after two successive homologous recombinations. The integration of each fibrinolytic gene into the middle of the amyE site was confirmed by phenotypes (Amy(-), Spec(S)) and colony PCR results for these strains. The fibrinolytic activities of the integrants were higher than that of B. subtilis 168 by at least 3.2-fold when grown in LB broth. Cheonggukjang was prepared by inoculating each of B. subtilis 168, SJ3-5nc, SJ176nc, and SJ179nc, and the fibrinolytic activity of cheonggukjang was 4.6 ± 0.7, 10.8 ± 0.9, 7.0 ± 0.6, and 8.0 ± 0.2 (U/g of cheonggukjang), respectively at 72 h. These results showed that construction of B. subtilis strains with enhanced fibrinolytic activities is possible by integration of a strong fibrinolytic gene via a marker-free manner.

  3. Effects of Breast Cancer and Mastectomy on Fibrinolytic Activity in ...

    African Journals Online (AJOL)

    It is good to know if this is also the case in Africans with breast cancer. Africans are known to possess enhanced fibrinolysis. This study was designed to assess the effect of breast cancer on fibrinolytic activity and the effect of mastectomy on fibrinolysis in African women. Sixty histo-patholically proven breast cancer patients ...

  4. Effect of supine exercise on platelet aggregation and fibrinolytic activity

    DEFF Research Database (Denmark)

    Dag, B; Fornitz, Gitte Gleerup; Bak, A M

    1994-01-01

    In 12 healthy young men, strenuous cycling exercise in the supine position, caused platelet aggregability to decrease and the ADP threshold to rise from 7.0 microM resting, to 9.5 exercising (P ... from 178 to 68 min, PAI-1 fell from 8.91 to 5.16 IU ml-1, and t-PA rose from 0.56 to 3.95 IU ml-1, all three values were significant to P exercise, it did not increase platelet activity as expected, but caused a modest increase...... of fibrinolytic activity. These results suggest that supine exercise will not affect the haemostatic system adversely....

  5. Human Protein C produces anticoagulation and increased fibrinolytic activity in the cat

    International Nuclear Information System (INIS)

    Burdick, M.D.; Schaub, R.G.

    1986-01-01

    The effect of activated human Protein C (PCa) infusion on the coagulation and fibrinolytic systems of the Nembutal anesthetized cat was assessed. Human Protein C was activated by incubation with thrombin or by passage over a column of thrombin immobilized on CNBr Sepharose 4B. Cats were given bolus i.v. injections of either vehicle or PCa in a dose range of 3-16 μg/mL of calculated whole body volume. Citrated blood samples (9:1) were taken from a femoral vein prior to and at 5, 10, 20, 30, 60, 120, and 180 min. after PCa. Activated partial thromboplastin time (APTT), thrombin time (TT) euglobulin clot lysis (ECLT) and I-125 fibrin release (FR) was measured. Vehicle treated cats had no change in any parameter. PCa produced a dose and time dependent prolongation of APTT while TT was unchanged. Anticoagulation was evident immediately after PCa infusion and began to normalize within 20 min. Fibrinolytic activity measured by ECLT and FR was also stimulated by PCa but was not evident until 40-60 minutes after PCa injection. The results show that human PCa induces anticoagulation effects in the cat similar to other species. However, stimulation of fibrinolysis requires a longer period of time before expression. This delay of fibrinolytic stimulation should be considered when assessing the effects of human Protein C in other species

  6. FIBRINOLYTIC-ACTIVITY IN THE ABDOMINAL-CAVITY OF RATS WITH FECAL PERITONITIS

    NARCIS (Netherlands)

    van Goor, Harry; de Graaf, JS; Sluiter, WJ; van der Meer, J; Bom, VJJ; Bleichrodt, RP

    Generalized peritonitis causes a reduction in abdominal fibrinolytic activity, resulting in persistence of intraabdominal fibrin with subsequent adhesion and abscess formation. The activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI) were measured in the

  7. Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thromboembolism

    International Nuclear Information System (INIS)

    Moroz, L.A.; MacLean, L.D.; Langleben, D.

    1986-01-01

    Fibrinolytic activities of whole blood and plasma were determined by 125 I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism

  8. Analysis of Proteolytic and Fibrinolytic Activity of the Blood Plasma in Patients with Bronchial Asthma Combined with Obesity

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    Fediv A.I. Fediv A.I.

    2016-09-01

    Full Text Available Aim of the study — to conduct the analysis of the performance of proteolytic and fibrinolytic activity of the blood plasma in patients with bronchial asthma (BA combined with obesity. Materials and methods. The study included 40 patients divided into groups. The basic group consisted of 20 patients with BA associated with obesity (ІI group, two comparison groups — of 10 patients with BA and normal body weight (I group and 10 patients with obesity and without pathology of the bronchopulmonary system (ІІІ group. Control group included 10 apparently healthy persons. In patients with BA, there were investigated the indexes of proteolytic and fibrinolytic activity of the blood plasma. Results. Analysis of the obtained data in patients with BA showed an increase of activity of plasma coagulation factors: total fibrinolytic activity increased in comparison to the control group, and in patients with BA it was 1.46 ± 0.13 Е440/ml/h, while in apparently healthy persons — 1.23 ± 0.16 Е440/ml/h (р < 0.05. In addition, an increase was marked and in the group of patients with the isolated obesity (by 38.5 % as compared to the group of apparently healthy persons, that can be explained by the growth of activity of inflammatory process due to the immune changes related to biological activity of fatty tissue as an additional source of proinflammatory cytokines. Conclusions. In combination of bronchial asthma and obesity, there is an activation of fibrinolytic and proteolytic systems of the blood that leads to microcirculatory and hemostatic disorders, enhancement of inflammatory process. In obesity as the state of systemic inflammatory response, the activation of fibrinolytic and proteolytic blood systems is more significant, than in bronchial asthma.

  9. PROTEOLYTIC AND FIBRINOLYTIC ACTIVITIES OF HALOPHILIC LACTIC ACID BACTERIA FROM TWO INDONESIAN FERMENTED FOODS

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    Asep A. Prihanto

    2013-04-01

    Full Text Available Exploration of fermented foods as sources of fibrinolytic enzymes is increased in the last decades. Terasi and Jambal roti is Indonesian traditional fermented fish products, which were famous in Java Island. Both are important products in Indonesian dishes, especially in Java. Investigation on halophilic lactic acid bacteria using MRS and M-17 agar obtained seventy four isolated strains. Their proteolytic and fibrinolytic activities were determined using skim milk agar and plasminogen-free fibrin plate. Twenty five isolates showed protease activities, while only four of them secreted fibrinolitic enzyme. The highest proteolytic and fibrinolytic activity was shown by TB1 strain, which is identified as Bacillus coagulans. The 16s rDNA is still in investigating to confirm the TB1 strain identity.

  10. The fibrinolytic mechanism of defibrotide: effect of defibrotide on plasmin activity.

    Science.gov (United States)

    Echart, Cinara L; Graziadio, Barbara; Somaini, Simona; Ferro, Laura I; Richardson, Paul G; Fareed, Jawed; Iacobelli, Massimo

    2009-12-01

    Fibrinolytic activity has been shown to be reduced in many vascular diseases, including hepatic veno-occlusive disease after stem cell transplantation, a microangiopathy characterized by sinusoidal endothelial cell injury. Defibrotide is a polydisperse oligonucleotide with antithrombotic, profibrinolytic, anti-ischemic, and antiadhesive properties. Numerous clinical studies have shown promising activity of defibrotide in the treatment and prevention of veno-occlusive disease, with minimal toxicity. In corollary laboratory studies, defibrotide has been shown to decrease plasminogen activator inhibitor-1, increase tissue plasminogen activator levels, and increase overall plasma fibrinolytic activity in patients. Plasmin, a potent and nonspecific serine protease, plays a pivotal role in fibrinolysis by virtue of its ability to effectively degrade fibrin clots. In this study, defibrotide increases the activity of plasmin in hydrolyzing its substrate in a dose-dependent and length-dependent manner. Similar concentration-dependent effects of defibrotide were observed when plasmin was generated by tissue plasminogen activator or urokinase activation of plasminogen. In contrast, defibrotide had no direct effect on the activation of plasminogen to plasmin. Defibrotide was also able to enhance the activity of plasmin in degrading fibrin clot formed from fibrinogen, plasminogen, and thrombin. This effect was also concentration-dependent and directly correlated with the enzymatic activity of plasmin. This study therefore demonstrates that defibrotide is capable of enhancing the activity of plasmin and so contributes to its fibrinolytic activity. Taken together, these results support the effect of defibrotide in restoring the fibrinolytic vascular phenotype, in microangiopathic conditions such as veno-occlusive disease.

  11. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase.

    Science.gov (United States)

    Sumi, H; Hamada, H; Nakanishi, K; Hiratani, H

    1990-01-01

    The existence of a potent fibrinolytic enzyme (nattokinase, NK) in the traditional fermented food called 'natto', was reported by us previously. It was confirmed that oral administration of NK (or natto) produced a mild and frequent enhancement of the fibrinolytic activity in the plasma, as indicated by the fibrinolytic parameters, and the production of tissue plasminogen activator. NK capsules were also administered orally to dogs with experimentally induced thrombosis, and lysis of the thrombi was observed by angiography. The results obtained suggest that NK represents a possible drug for use not only in the treatment of embolism but also in the prevention of the disease, since NK has a proven safety and can be massproduced.

  12. Fibrinolytic activity is associated with presence of cystic media degeneration in aneurysms of the ascending aorta

    OpenAIRE

    Borges , Luciano F; Gomez , Delphine; Quintana , Mercedes; Leclercq , Anne; Touat , Ziad; Jondeau , Guillaume; Meilhac , Olivier; Jandrot-Perrus , Martine; Gutierrez , Paulo Sampaio; Freymuller , Edna; Vranckx , Roger; Michel , Jean-Baptiste

    2010-01-01

    Abstract Aims Thoracic Ascending Aortic Aneurysms (TAA) are characterized by elastic fibre breakdown and cystic medial degeneration within the aortic media, associated with progressive SMC rarefaction. The TGF-?/Smad2 signaling pathway is involved in this process. Since pericellular fibrinolytic system activation is able to degrade adhesive proteins, activate MMPs, induce SMC disappearance and increase the bio-availability of TGF-?, we explored the plasminergic system in TAA. ...

  13. Directed evolution improves the fibrinolytic activity of nattokinase from Bacillus natto.

    Science.gov (United States)

    Yongjun, Cai; Wei, Bao; Shujun, Jiang; Meizhi, Weng; Yan, Jia; Yan, Yin; Zhongliang, Zheng; Goulin, Zou

    2011-12-01

    Nattokinase (subtilisin NAT, NK) is a relatively effective microbial fibrinolytic enzyme that has been identified and characterized from Bacillus natto. In the current report, DNA family shuffling was used to improve the fibrinolytic activity of nattokinase. Three homologous genes from B. natto AS 1.107, Bacillus amyloliquefaciens CICC 20164 and Bacillus licheniformis CICC 10092 were shuffled to generate a mutant library. A plate-based method was used to screen the mutant libraries for improved activity. After three rounds of DNA shuffling, one desirable mutant with 16 amino acid substitutions was obtained. The mutant enzyme was purified and characterized. The kinetic measurements showed that the catalytic efficiency of the mutant NK was approximately 2.3 times higher than that of the wild-type nattokinase. In addition, the molecular modeling analysis suggested that the mutations affect the enzymatic function by changing the surface conformation of the substrate-binding pocket. The current study shows that the evolution of nattokinase with improved fibrinolytic activity by DNA family shuffling is feasible and provides useful references to facilitate the application of nattokinase in thrombolytic therapy. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  14. The Antithrombotic and Fibrinolytic Effect of Natto in Hypercholesterolemia Rats

    OpenAIRE

    Park, Kum-Ju; Kang, Jung Il; Kim, Tae-Seok; Yeo, Ik-Hyun

    2012-01-01

    Antithrombotic and fibrinolytic activity of natto was evaluated on platelet aggregation in vitro and in vivo. Natto showed inhibitory effects on platelet aggregation induced by adenosine 5′diphosphate (ADP) and collagen. Orally administered natto also showed fibrinolytic activity in hypercholesterolemia rats. Normal levels of natto, when administered for four weeks, shortened euglobulin clot lysis time (ECLT) and prolonged partial thromboplastin time (PATT) significantly compared to non-treat...

  15. Fibrinolytic and procoagulant activities of Yersinia pestis and Salmonella enterica.

    Science.gov (United States)

    Korhonen, T K

    2015-06-01

    Pla of the plague bacterium Yersinia pestis and PgtE of the enteropathogen Salmonella enterica are surface-exposed, transmembrane β-barrel proteases of the omptin family that exhibit a complex array of interactions with the hemostatic systems in vitro, and both proteases are established virulence factors. Pla favors fibrinolysis by direct activation of plasminogen, inactivation of the serpins plasminogen activator inhibitor-1 and α2-antiplasmin, inactivation of the thrombin-activable fibrinolysis inhibitor, and activation of single-chain urokinase. PgtE is structurally very similar but exhibits partially different functions and differ in expression control. PgtE proteolysis targets control aspects of fibrinolysis, and mimicry of matrix metalloproteinases enhances cell migration that should favor the intracellular spread of the bacterium. Enzymatic activity of both proteases is strongly influenced by the environment-induced variations in lipopolysaccharide that binds to the β-barrel. Both proteases cleave the tissue factor pathway inhibitor and thus also express procoagulant activity. © 2015 International Society on Thrombosis and Haemostasis.

  16. Fibrinolytic Activity and Dose-Dependent Effect of Incubating Human Blood Clots in Caffeic Acid Phenethyl Ester: In Vitro Assays

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    Abuzar Elnager

    2015-01-01

    Full Text Available Background. Caffeic acid phenethyl ester (CAPE has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM. After 3 hours, D-dimer (DD levels and WB clot weights were measured for each concentration. Thromboelastography (TEG parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM. The 50% effective dose (ED50 of CAPE (based on DD was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.

  17. Clinical Importance of Angiogenic Cytokines, Fibrinolytic Activity and Effusion Size in Parapneumonic Effusions

    Science.gov (United States)

    Chung, Chi-Li; Hsiao, Shih-Hsin; Hsiao, George; Sheu, Joen-Rong; Chen, Wei-Lin; Chang, Shi-Chuan

    2013-01-01

    Objective To investigate the relationship among angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusion (PPE) and their clinical importance. Methods From January 2008 through December 2010, 26 uncomplicated (UPPE) and 38 complicated (CPPE) PPE were studied. Based on chest ultrasonography, there were non-loculated in 30, uni-loculated in 12, and multi-loculated effusions in 22 patients. The effusion size radiological scores, and effusion vascular endothelial growth factor (VEGF), interleukin (IL)-8, plasminogen activator inhibitor type-1 (PAI-1) and tissue type plasminogen activator (tPA) were measured on admission. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT), were assessed at 6-month follow-up. Results The effusion size and effusion VEGF, IL-8 and PAI-1/tPA ratio were significantly higher in CPPE than in UPPE, and significantly higher in multi-loculated PPE than in non-locualted and uni-loculated PPE, respectively. VEGF (cutoff value 1975 pg/ml) and IL-8 (cutoff value 1937 pg/ml) seemed best to discriminate between UPPE and CPPE. VEGF, IL-8 and effusion size correlated positively with PAI-1/tPA ratio in both UPPE and CPPE. Moreover, the level of VEGF, but not IL-8, correlated positively with effusion size in all patients (r = 0.79, peffusion were prone to have medical treatment failure (n = 10; VEGF, odds ratio 1.01, p = 0.02; effusion size, odds ratio 1.26, p = 0.01). Additionally, ten patients with RPT had larger effusion size and higher levels of VEGF and PAI-1/tPA ratio than did those without. Conclusions In PPE, VEGF and IL-8 levels are valuable to identify CPPE, and higher VEGF level or larger effusion is associated with decreased fibrinolytic activity, development of pleural loculation and fibrosis, and higher risk of medical treatment failure. PMID:23308155

  18. Blood Fibrinolytic Activity in Patients with Type 2 Diabetes Mellitus Associated with Hypothyroidism

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    Т.Yu. Yuzvenko

    2015-04-01

    Full Text Available The objective of the research was to study the level of plasminogen activator inhibitor type 1 (PAI-1 in the blood serum of patients with type 2 diabetes mellitus (DM in combination with hypothyroidism. We have observed 62 patients with type 2 DM, 32 of them had primary hypothyroidism. Control group consisted of 20 persons without carbohydrate metabolism disorders and thyroid pathology. In patients with type 2 DM, we have detected violations in the fibrinolytic system as an increase of PAI-1, whose level depends on the body mass index, waist circumference, level of glycated haemoglobin, indexes of insulin resistance, blood lipid spectrum, as well as on the presence of microalbuminuria. The presence of hypothyroidism has an additional negative impact on the parameters of carbohydrate, lipid metabolism and PAI-1 level in patients with type 2 DM.

  19. Static magnetic field effects on proteases with fibrinolytic activity produced by Mucor subtilissimus.

    Science.gov (United States)

    Albuquerque, Wendell; Nascimento, Thiago; Brandão-Costa, Romero; Fernandes, Thiago; Porto, Ana

    2017-02-01

    The influence of a static magnetic field (SMF) on crude enzyme extracts with proteolytic activity is described and discussed. Proteolytic enzymes, which hydrolyze peptide bonds, and fibrinolytic enzymes, which dissolve fibrin clots, have industrial relevance, and applicability dependent on improvements of productivity and activity. We investigated whether a moderate SMF affects proteolysis in different in vitro tests: general proteolysis of azocasein substrate, and static and dynamic fibrinolytic processes (to compare fibrin gel configuration under exposure). Crude enzyme extracts, obtained from solid state fermentation of Mucor subtilissimus UCP (Universidade Católica de Pernambuco, Recife, Brazil) 1262, were used to carry out assays under slightly heterogeneous fields: a varied vertical SMF (for tests in Eppendorf tubes, from 0.100 to 0.170 T) and a varied horizontal SMF (for tests in Petri dishes, from 0.01 to 0.122 T), generated by two permanent magnets (NdFeB alloy). Results showed significant differences (P < 0.05) in static fibrinolysis assays after 24 h of exposure. The mean diameter of halos of fibrin degradation in the treated group increased by 21% compared to the control group; and the pixel number count of fibrin consumption (in a computational analysis of the area of each halo) enhanced by 30% with exposure. However, in dynamic fibrinolysis assays, no effects of SMF were observed. These results suggest a response of fibrin monomers to the SMF as a possible cause of the observed effects. Bioelectromagnetics. 38:109-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Clinical importance of angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusions.

    Directory of Open Access Journals (Sweden)

    Chi-Li Chung

    Full Text Available OBJECTIVE: To investigate the relationship among angiogenic cytokines, fibrinolytic activity and effusion size in parapneumonic effusion (PPE and their clinical importance. METHODS: From January 2008 through December 2010, 26 uncomplicated (UPPE and 38 complicated (CPPE PPE were studied. Based on chest ultrasonography, there were non-loculated in 30, uni-loculated in 12, and multi-loculated effusions in 22 patients. The effusion size radiological scores, and effusion vascular endothelial growth factor (VEGF, interleukin (IL-8, plasminogen activator inhibitor type-1 (PAI-1 and tissue type plasminogen activator (tPA were measured on admission. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT, were assessed at 6-month follow-up. RESULTS: The effusion size and effusion VEGF, IL-8 and PAI-1/tPA ratio were significantly higher in CPPE than in UPPE, and significantly higher in multi-loculated PPE than in non-locualted and uni-loculated PPE, respectively. VEGF (cutoff value 1975 pg/ml and IL-8 (cutoff value 1937 pg/ml seemed best to discriminate between UPPE and CPPE. VEGF, IL-8 and effusion size correlated positively with PAI-1/tPA ratio in both UPPE and CPPE. Moreover, the level of VEGF, but not IL-8, correlated positively with effusion size in all patients (r = 0.79, p<0.001 and in UPPE (r = 0.64, p<0.001 and CPPE (r = 0.71, p<0.001 groups. The patients with higher VEGF or greater effusion were prone to have medical treatment failure (n = 10; VEGF, odds ratio 1.01, p = 0.02; effusion size, odds ratio 1.26, p = 0.01. Additionally, ten patients with RPT had larger effusion size and higher levels of VEGF and PAI-1/tPA ratio than did those without. CONCLUSIONS: In PPE, VEGF and IL-8 levels are valuable to identify CPPE, and higher VEGF level or larger effusion is associated with decreased fibrinolytic activity, development of pleural loculation and fibrosis, and higher risk of medical treatment failure.

  1. Purification and characterization of a serine protease (CPM-2) with fibrinolytic activity from the dung beetles.

    Science.gov (United States)

    Ahn, Mi Young; Hahn, Bum-Soo; Ryu, Kang Sun; Hwang, Jae Sam; Kim, Yeong Shik

    2005-07-01

    Catharsius protease-2 (CPM-2) was isolated from the body of dung beetles, Catharsius molossus, using a three step purification process (ammonium sulfate fractionation, gel filtration on Bio-Gel P-60, and affinity chromatography on DEAE Affi-Gel blue). The purified CPM-2, having a molecular weight of 24 kDa, was assessed homogeneously by SDS-polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of CPM-2 was composed of X Val Gln Asp Phe Val Glu Glu Ile Leu. CPM-2 was inactivated by Cu2+ and Zn2+ and strongly inhibited by typical serine proteinase inhibitors such as TLCK, soybean trypsin inhibitor, aprotinin, benzamidine, and alpha1-antitrypsin. However, EDTA, EGTA, cysteine, beta-mercaptoethanol, E64, and elastatinal had little effect on enzyme activity. In addition, antiplasmin and antithrombin III were not sensitive to CPM-2. Based on the results of a fibrinolytic activity test, CPM-2 readily cleaved Aalpha- and Bbeta-chains of fibrinogen and fibrin, and gamma-chain of fibrinogen more slowly. The nonspecific action of the enzyme resulted in extensive hydrolysis, releasing a variety of fibrinopeptides of fibrinogen and fibrin. Polyclonal antibodies of CPM-2 were reactive to the native form of antigen. The ELISA was applied to detect quantities, in nanograms, of the antigen in CPM-2 protein.

  2. Secapin, a bee venom peptide, exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities.

    Science.gov (United States)

    Lee, Kwang Sik; Kim, Bo Yeon; Yoon, Hyung Joo; Choi, Yong Soo; Jin, Byung Rae

    2016-10-01

    Bee venom contains a variety of peptide constituents that have various biological, toxicological, and pharmacological actions. However, the biological actions of secapin, a venom peptide in bee venom, remain largely unknown. Here, we provide the evidence that Asiatic honeybee (Apis cerana) secapin (AcSecapin-1) exhibits anti-fibrinolytic, anti-elastolytic, and anti-microbial activities. The recombinant mature AcSecapin-1 peptide was expressed in baculovirus-infected insect cells. AcSecapin-1 functions as a serine protease inhibitor-like peptide that has inhibitory effects against plasmin, elastases, microbial serine proteases, trypsin, and chymotrypsin. Consistent with these functions, AcSecapin-1 inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products, thus indicating the role of AcSecapin-1 as an anti-fibrinolytic agent. AcSecapin-1 also inhibited both human neutrophil and porcine pancreatic elastases. Furthermore, AcSecapin-1 bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi and gram-positive and gram-negative bacteria. Taken together, our data demonstrated that the bee venom peptide secapin has multifunctional roles as an anti-fibrinolytic agent during fibrinolysis and an anti-microbial agent in the innate immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Gene expression of fibrinolytic factors urokinase plasminogen activator and plasminogen activator inhibitor-1 in rabbit temporo-mandibular joint cartilage with disc displacement.

    Science.gov (United States)

    Zhan, Jing; Gu, Zhi-yuan; Wu, Li-qun; Zhang, Yin-kai; Hu, Ji-an

    2005-06-20

    The urokinase plasminogen activator system is believed to play an important role in degradation of the extracellular matrix associated with cartilage and bone destruction; however its precise roles in temporomandibular disorders have not yet been clarified. The aims of this study were to investigate the gene expression of fibrinolytic factors urokinase plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the articular cartilage of rabbit temporomandibular joint (TMJ) with disc displacement (DD) and to probe the relationship between fibrinolytic activity and cartilage remodeling. Disc displacement of right joints was performed in 36 of 78 rabbits under investigation. The animals were sacrificed at 4 days and 1, 2, 4, 8 and 12 weeks after surgery, respectively. The right joints of these animals were harvested and processed for the examination of mRNA expression of uPA and PAI-1 in articular cartilage using in situ hybridization techniques. The expression of uPA and PAI-1 was co-expressed weakly in the chondrocytes from transitive zone to hypertrophic zone and mineralized zone, while no hybridizing signals were shown in proliferative zone and superficial zone in control rabbits. The most striking was the up-regulation of uPA and PAI-1 mRNA in 4-day rabbits postoperatively at the onset of cartilage degeneration. The strongest hybridizing signals for uPA and PAI-1 were seen in 2-week rabbits postoperatively. After 2 weeks, the expression of uPA and PAI-1 began to decrease and reached nearly normal level at 12 weeks. The expression of the uPA/PAI-1 system coincides with the pathological changes in condylar cartilage after DD. The uPA/PAI-1 system may be one of the essential mediators in articular cartilage remodeling.

  4. Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

    Science.gov (United States)

    Vuckovic, Biljana A; Djeric, Mirjana J; Tomic, Branko V; Djordjevic, Valentina J; Bajkin, Branislav V; Mitic, Gorana P

    2018-01-01

    : Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.

  5. Highly potent fibrinolytic serine protease from Streptomyces.

    Science.gov (United States)

    Uesugi, Yoshiko; Usuki, Hirokazu; Iwabuchi, Masaki; Hatanaka, Tadashi

    2011-01-05

    We introduce a highly potent fibrinolytic serine protease from Streptomyces omiyaensis (SOT), which belongs to the trypsin family. The fibrinolytic activity of SOT was examined using in vitro assays and was compared with those of known fibrinolytic enzymes such as plasmin, tissue-type plasminogen activator (t-PA), urokinase, and nattokinase. Compared to other enzymes, SOT showed remarkably higher hydrolytic activity toward mimic peptides of fibrin and plasminogen. The fibrinolytic activity of SOT is about 18-fold higher than that of plasmin, and is comparable to that of t-PA by fibrin plate assays. Furthermore, SOT had some plasminogen activator-like activity. Results show that SOT and nattokinase have very different fibrinolytic and fibrinogenolytic modes, engendering significant synergetic effects of SOT and nattokinase on fibrinolysis. These results suggest that SOT presents important possibilities for application in the therapy of thrombosis. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Effects of carbon dioxide level (PCO2) on the fibrinolytic activity (FA) of pulmonary artery endothelial cells (PAEC)

    International Nuclear Information System (INIS)

    Langleben, D.; Moroz, L.A.; Danes, D.

    1990-01-01

    Recovery from pulmonary thromboembolism depends on the rapidity and completeness of clot lysis. This involves endogenous fibrinolytic mechanisms, particularly the balance between plasminogen activators and inhibitors produced by endothelial cells. Hypocapnia is common in pulmonary embolism, however it is not known if endothelial fibrinolytic function is affected by PCO 2 . The authors therefore measured the FA in medium (MCDB-131, 0.5% albumin) conditioned for 20 hours in-vitro by exposure to confluent cultures of bovine proximal PAEC. During conditioning, cells were exposed to 5% CO 2 in air (PCO 2 - 36-40mm Hg, CONTROL), or various PCO 2 levels (30-55 mmHg, in air). FA of conditioned medium was determined by 125 I-fibrin solid phase assay, with addition of plasminogen (10 ug/ml). With PCO 2 levels ≤ 35 mmHg, FA in the conditioned medium was 5 to 18% higher than CONTROL FA. When PCO 2 was ≥ 45 mmHg, FA decreased 5 to 60% as compared to CONTROL FA. There was a significant negative linear relationship between PCO 2 and FA. Thus, PCO 2 level can affect PAEC mediated plasminogen activation. This finding may be relevant to in-vivo clearance of clots from pulmonary arteries

  7. Effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Xiao-Li Zhu

    2016-05-01

    Full Text Available Objective: To observe the effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome (ACS. Methods: A total of 92 patients with ACS were randomly divided into observation group (47 cases and control group (45 cases. The control group was given Atorvastatin (10mg/d based on the conventional therapy, while the observation group was given Atorvastatin at an intensive dose (40 mg/d based on the conventional therapy. Half a month later, the changes of IL-6, IL-8, hs-CRP, TNF-α, TXB2, GMP-140, PAI-1 and t-PA were observed and compared between the two groups. Results: After treatment, the inflammatory factors (IL-6, IL-8, hs-CRP and TNF-α and the indicators of platelet activity (TXB2, GMP-140 and PAI-1 were obviously decreased, while the indicator of fibrinolytic activity (t-PA was apparently increased in the two groups. Besides, the amplitudes of change referring to these indicators in the observation group were bigger than those in the control group after treatment, and the differences were statistically significant. Conclusion: The intensive therapy with the administration of Atorvastatin at a dose of 40 mg/d was better than the conventional therapy (Atorvastatin: 10 mg/d in aspects of reducing inflammatory factors, inhibiting platelet activity and correcting the high coagulation state of fibrinolytic system.

  8. Characterization of Fibrinolytic Proteases from Gloydius blomhoffii siniticus Venom

    Directory of Open Access Journals (Sweden)

    Suk Ho Choi

    2011-09-01

    Full Text Available Objectives : This study was undertaken to identify fibrinolytic proteases from Gloydius blomhoffii siniticus venom and to characterize a major fibrinolytic protease purified from the venom. Methods: The venom was subjected to chromatography using columns of Q-Sepharose and Sephadex G-75. The molecular weights of fibrinolytic proteases showing fibrinolytic zone in fibrin plate assay were determined in SDS-PAGE (Sodium dodecyl sulfate-polyacrylamide gel electrophoresis The effects of inhibitors and metal ions on fibrinolytic protease and the proteolysis patterns of fibrinogen, gelatin, and bovine serum albumin were investigated. Results : 1 The fibrinolytic fractions of the three peaks isolated from Gloydius blomhoffii siniticus venom contained two polypeptides of 46 and 59 kDa and three polypeptides of 32, 18, and 15 kDa and a major polypeptide of 54 kDa, respectively. 2 The fibrinolytic activity of the purified protease of 54 kDA was inhibited by metal chelators, such as EDTA, EGTA, and 1,10-phenanthroline, and disulfhydryl-reducing compounds, such as dithiothreitol and cysteine. 3 Calcium chloride promoted the fibrinolytic activity of the protease, but mercuric chloride and cobalt(II chloride inhibited it. 4 The fibrinolytic protease cleaved preferentially A-chain and slowly B-chain of fibrinogen. It also hydrolyzed gelatin but not bovine serum albumin. Conclusions: The Gloydius blomhoffii siniticus venom contained more than three fibrinolytic proteases. The major fibrinolytic protease was a metalloprotease which hydrolyzed both fibrinogen and gelatin, but not bovine serum albumin.

  9. Anti-fibrinolytic and anti-microbial activities of a serine protease inhibitor from honeybee (Apis cerana) venom.

    Science.gov (United States)

    Yang, Jie; Lee, Kwang Sik; Kim, Bo Yeon; Choi, Yong Soo; Yoon, Hyung Joo; Jia, Jingming; Jin, Byung Rae

    2017-10-01

    Bee venom contains a variety of peptide constituents, including low-molecular-weight protease inhibitors. While the putative low-molecular-weight serine protease inhibitor Api m 6 containing a trypsin inhibitor-like cysteine-rich domain was identified from honeybee (Apis mellifera) venom, no anti-fibrinolytic or anti-microbial roles for this inhibitor have been elucidated. In this study, we identified an Asiatic honeybee (A. cerana) venom serine protease inhibitor (AcVSPI) that was shown to act as a microbial serine protease inhibitor and plasmin inhibitor. AcVSPI was found to consist of a trypsin inhibitor-like domain that displays ten cysteine residues. Interestingly, the AcVSPI peptide sequence exhibited high similarity to the putative low-molecular-weight serine protease inhibitor Api m 6, which suggests that AcVSPI is an allergen Api m 6-like peptide. Recombinant AcVSPI was expressed in baculovirus-infected insect cells, and it demonstrated inhibitory activity against trypsin, but not chymotrypsin. Additionally, AcVSPI has inhibitory effects against plasmin and microbial serine proteases; however, it does not have any detectable inhibitory effects on thrombin or elastase. Consistent with these inhibitory effects, AcVSPI inhibited the plasmin-mediated degradation of fibrin to fibrin degradation products. AcVSPI also bound to bacterial and fungal surfaces and exhibited anti-microbial activity against fungi as well as gram-positive and gram-negative bacteria. These findings demonstrate the anti-fibrinolytic and anti-microbial roles of AcVSPI as a serine protease inhibitor. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. On fibrinolytic phenomenon in the cancerous tissue of cervical carcinoma with special reference to irradiation changes

    International Nuclear Information System (INIS)

    Nakamura, Kazuyoshi

    1978-01-01

    In a study undertaken to investigate alterations of fibrinolytic enzymes in cancerous tissue of the cervix under radiotherapy, specimens were taken from malignant tissues of cervical cancer patients during irradiation therapy with Linac x-ray at 1000, 2000 and 3000 rads and were subsequently assayed for fibrinolytic enzyme activities using the fibrin plate method. No plasmin activity was demonstrable in the normal mucosa of the uterine cervix. Cancerous tissue of the uterine cervix also showed no demonstrable plasmin activity. The malignant tissue, as compared to the normal mucosa of the cervix, was found to have a lower activator activity, a higher proactivator activity and lower activities of both antiplasmin inhibitors. During radiotherapy for cervical cancer, plasmin activity was demonstrable in the cancerous tissue and in patients with malignant neoplasm, demonstrating that plasmin activity increased as the radiation dose was increased. A relationship seemed to exist between morphological changes and alterations in the fibrinolytic system of cancerous tissue of the cervix. From these findings it seems that the altered fibrinolytic enzyme system in cancerous tissue may have a close relationship with the growth and development of malignancy and may also have an important role in the occurrence of metastasis. There were some cases, in which an abnormal increase in activator activity occurred during irradiation therapy, leading to the death of the patients. This fact points to the possibility that activator activity might provide a useful index for evaluating the prognosis of cervical cancer. (author)

  11. Studies on screening, isolation and purification of a fibrinolytic protease from an isolate (VK12) of Ganoderma lucidum and evaluation of its antithrombotic activity.

    Science.gov (United States)

    Kumaran, Sekar; Palani, Perumal; Nishanthi, Ramasami; Kaviyarasan, Venkatesan

    2011-01-01

    Antithrombotic activity of a protease purified from a medicinal mushroom, Ganoderma lucidum, has been evaluated platelet aggregation in vitro and pulmonary thrombosis in vivo. The purified protease exhibited concentration dependent inhibitory effects on platelet aggregation induced by ADP (adenosine diphosphate), with an IC(50) value of 2.4 mg/mL. The purified protease protected mice against thrombotic death or paralysis induced by collagen and epinephrine in a dose dependent manner when administered orally. It produced a significant inhibition of thrombotic death or paralysis at 60 µg/kg body weight, while aspirin produced a significant inhibition of thrombosis at 10-20 mg/kg body weight. The purified protease also has showed fibrinolytic activity and alters coagulation parameters such as activated partial thromboplastin time (APTT), and thrombin time (TT) in rat platelet. These results suggested that the antithrombotic activity of Ganoderma lucidum protease might be due to antiplatelet activity rather than anticoagulation activity.

  12. Optimization of alkaline protease production and its fibrinolytic ...

    African Journals Online (AJOL)

    Optimization of alkaline protease production and its fibrinolytic activity from the ... nitrogen sources and sodium chloride concentration for protease production by the ... exploited to assist in protein degradation in various industrial processes.

  13. The effect of chemical anti-inhibitors on fibrinolytic enzymes and inhibitors

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, J; Kluft, C

    1997-01-01

    proteases. We studied the influence of chemical anti-inhibitors (chloramine T, flufenamate, sodium lauryl sulfate, and methylamine) on fibrinolytic serine proteases and fibrinolytic enzyme inhibitors using the physiological substrate fibrin as plasmin substrate. Low concentrations of chloramine T (0.01 mmol......%) and plasminogen activators (apparent recovery > 200%). Sodium lauryl sulfate eliminates the major fibrinolytic enzyme inhibitors, but increases the activity of plasmin (apparent recovery > 200%) and plasminogen activator, urokinase type (apparent recovery 130%). Methylamine affects only plasmin inhibition. We...

  14. Fibrin(ogen) is internalized and degraded by activated human monocytoid cells via Mac-1 (CD11b/CD18): a nonplasmin fibrinolytic pathway.

    Science.gov (United States)

    Simon, D I; Ezratty, A M; Francis, S A; Rennke, H; Loscalzo, J

    1993-10-15

    Fibrin(ogen) (FGN) is important for hemostasis and wound healing and is cleared from sites of injury primarily by the plasminogen activator system. However, there is emerging evidence in plasminogen activator-deficient transgenic mice that nonplasmin pathways may be important in fibrin(ogen)olysis, as well. Given the proximity of FGN and monocytes within the occlusive thrombus at sites of vascular injury, we considered the possibility that monocytes may play an ancillary role in the degradation and clearance of fibrin. We found that monocytes possess an alternative fibrinolytic pathway that uses the integrin Mac-1, which directly binds and internalizes FGN, resulting in its lysosomal degradation. At 4 degrees C, FGN binds to U937 monocytoid cells in a specific and saturable manner with a kd of 1.8 mumol/L. Binding requires adenosine diphosphate stimulation and is calcium-dependent. At 37 degrees C, FGN and fibrin monomer (FM) are internalized and degraded at rates of 0.37 +/- 0.13 and 0.55 +/- 0.03 microgram/10(6) cells/h by U937 cells, 1.38 +/- 0.02 and 1.20 +/- 0.30 microgram/10(6) cells/h by THP-1 cells, and 2.10 +/- 0.20 and 2.52 +/- 0.18 micrograms/10(6) cells/h by human peripheral blood mononuclear cells, respectively. The serine protease inhibitors, PPACK and aprotinin, and the specific elastase inhibitor, AAPVCK, do not significantly inhibit degradation. However, degradation is inhibited by chloroquine, suggesting that a lysosomal pathway is involved. Factor X, a competitive ligand with FGN for the Mac-1 receptor, also blocks degradation, as does a monoclonal antibody to the alpha-subunit of Mac-1. Autoradiography of radioiodinated, internalized FGN shows that FGN proteolysis by the pathway produces a unique degradation pattern distinct from that observed with plasmin. In a fibrin clot lysis assay, Mac-1-mediated fibrinolysis contributed significantly to total fibrinolysis. In summary, FGN is internalized and degraded by activated human monocytoid cells via

  15. Purification of an Intracellular Fibrinolytic Protease from Ganoderma ...

    African Journals Online (AJOL)

    Result: The fibrinolytic enzyme isolated from Ganoderma lucidum was purified to near homogeneity and it appeared as a single protein band on SDS-PAGE. Metal ions such as Ca2+ and Mg2+ inhibited the activity of the enzyme while Zn2+ ions enhanced the activity. Complete inactivation occurred when the enzyme was ...

  16. Global fibrinolytic activity, PAI-1 level, and 4G/5G polymorphism in Thai children with arterial ischemic stroke.

    Science.gov (United States)

    Natesirinilkul, Rungrote; Sasanakul, Werasak; Chuansumrit, Ampaiwan; Kadegasem, Praguywan; Visudtibhan, Anannit; Wongwerawattanakoon, Pakawan; Sirachainan, Nongnuch

    2014-01-01

    Prolonged euglobulin clot lysis time (ECLT) and increased level of plasminogen activator inhibitor-1 (PAI-1) were reported to be risk factors of arterial ischemic stroke (AIS) by some studies; however, these findings were not supported by other studies. The objective of this study was to determine the association of ECLT, PAI-1 level, and polymorphisms of 4G and 5G of PAI-1 gene to the development of AIS in Thai children. This study included patients aged 1-18 years old. Diagnosis of AIS was confirmed by imaging study. The control group was age- and sex-matched healthy subjects. Demographic data were recorded, and blood was tested for ECLT, PAI-1 level, lipid profiles, fasting blood sugar (FBS), and 4G and 5G polymorphisms of PAI-1 gene. There were 70 subjects participating in this study, consisting of 30 patients and 40 controls. Demographic data, lipid profiles, and FBS were similar between the 2 groups. Furthermore, ECLT and PAI-1 level did not differ between patient and control groups; however, both showed significant correlation (r = .352, P = .006). The 4G/5G polymorphism was the most common genotype in both patient and control groups (69.0% vs. 80.0%). However, 4G and 5G polymorphisms of PAI-1 gene did not correlate with PAI-1 level in this study (P = .797). The PAI-1 level and 4G/5G polymorphism may not be a risk factor of AIS in this population. It was also found that the 4G/5G polymorphism was the most common PAI-1 genotype in this study. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  17. PRODUCTION OF FIBRINOLYTIC ENZYME (NATTOKINASE) FROM BACILLUS SP.

    OpenAIRE

    Padma Singh, Rekha Negi*, Vani Sharma, Alka Rani, Pallavi and Richa Prasad

    2018-01-01

    During present study Nattokinase which is a novel fibrinolytic enzyme was produced by Bacillus sp. To screen and extract nattokinase enzyme from Bacillus sp. were isolated from soil of different agricultural field by serial dilution method. Out of 10 isolate, one strain i.e. B3 produced nattokinase on screening medium. B3 was identified by biochemical characterization. The caseinolytic activity of Nattokinase was 0.526 U/ml and the selected isolate Bacillus sp. could produce active nattokinas...

  18. Production, optimization and characterization of fibrinolytic enzyme by Bacillus subtilis RJAS19.

    Science.gov (United States)

    Kumar, D J Mukesh; Rakshitha, R; Vidhya, M Annu; Jennifer, P Sharon; Prasad, Sandip; Kumar, M Ravi; Kalaichelvan, P T

    2014-04-01

    The present study aimed at the production, purification and characterization of fibrinolytic nattokinase enzyme from the bacteria isolated from natto food. For the purpose, a fibrinolytic bacterium was isolated and identified as Bacillus subtilis based on 16S rDNA sequence analysis. The strain was employed for the production and optimization of fibrinolytic enzyme. The strain showed better enzyme production during 72nd h of incubation time with 50 degrees C at the pH 9. The lactose and peptone were found to be increasing the enzyme production rate. The enzyme produced was purified and also characterized with the help of SDS-PAGE analysis. The activity and stability profile of the purified enzyme was tested against different temperature and pH. The observations suggesting that the potential of fibrinolytic enzyme produced by Bacillus subtilis RJAS 19 for its applications in preventive medicines.

  19. Intrapleural agents for pleural infection: fibrinolytics and beyond.

    Science.gov (United States)

    Rahman, Najib M

    2012-07-01

    Pleural infection is a common, increasing clinical problem with a high morbidity and mortality. Medical management of pleural infection often fails, requiring invasive thoracic surgery to drain infected pleural collections, and for many years intrapleural agents have been assessed to reduce the need for surgical drainage and improve clinical outcomes. Randomized trials assessing intrapleural fibrinolytic agents have given conflicting results, and recent evidence provides important information on the role of intrapleural agents in the treatment of pleural infection, and the possible biology associated with infection progression in these patients. Pleural infection is increasing in both the adult and paediatric populations. The combined previous evidence assessing intrapleural fibrinolytics alone in pleural infection suggests lack of efficacy for clinically important outcomes. The Multi-Centre Intrapleural Sepsis Trial 2 (MIST2) study provides the first evidence of a novel treatment combination [intrapleural tissue plasminogen activator (tPA) combined with intrapleural deoxyribonuclease (DNase)], which significantly improves the chest radiograph compared with either agent alone or placebo, and has potentially important benefits to important clinical outcomes (need for surgery and hospital stay). The precise mechanism of action of combination fibrinolytic and DNase in pleural infection is speculative. Fibrinolytic therapy alone has not been proven to be of use in the treatment of pleural infection. The MIST2 study provides clear-cut evidence demonstrating improved chest radiographs, and highly suggestive secondary outcomes suggesting improved clinically important outcomes, using a combination of intrapleural tPA and DNase. This novel treatment combination may represent an important step in our understanding and treatment of pleural infection; however, larger clinical studies specifically addressing important clinical outcomes and further laboratory research describing

  20. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet.

    Science.gov (United States)

    Sumi, H; Hamada, H; Tsushima, H; Mihara, H; Muraki, H

    1987-10-15

    A strong fibrinolytic activity was demonstrated in the vegetable cheese Natto, which is a typical soybean food eaten in Japan. The average activity was calculated at about 40 CU (plasmin units)/g wet weight. This novel fibrinolytic enzyme, named nattokinase, was easily extracted with saline. The mol. wt and pI were about 20,000 and 8.6, respectively. Nattokinase not only digested fibrin but also the plasmin substrate H-D-Val-Leu-Lys-pNA (S-2251), which was more sensitive to the enzyme than other substrates tried. Diisopropyl fluorophosphate and 2,2,2-trichloro-1-hydroxyethyl-o,o-dimethylphosphate strongly inhibited this fibrinolytic enzyme.

  1. The Inflammatory Actions of Coagulant and Fibrinolytic Proteases in Disease

    Directory of Open Access Journals (Sweden)

    Michael Schuliga

    2015-01-01

    Full Text Available Aside from their role in hemostasis, coagulant and fibrinolytic proteases are important mediators of inflammation in diseases such as asthma, atherosclerosis, rheumatoid arthritis, and cancer. The blood circulating zymogens of these proteases enter damaged tissue as a consequence of vascular leak or rupture to become activated and contribute to extravascular coagulation or fibrinolysis. The coagulants, factor Xa (FXa, factor VIIa (FVIIa, tissue factor, and thrombin, also evoke cell-mediated actions on structural cells (e.g., fibroblasts and smooth muscle cells or inflammatory cells (e.g., macrophages via the proteolytic activation of protease-activated receptors (PARs. Plasmin, the principle enzymatic mediator of fibrinolysis, also forms toll-like receptor-4 (TLR-4 activating fibrin degradation products (FDPs and can release latent-matrix bound growth factors such as transforming growth factor-β (TGF-β. Furthermore, the proteases that convert plasminogen into plasmin (e.g., urokinase plasminogen activator evoke plasmin-independent proinflammatory actions involving coreceptor activation. Selectively targeting the receptor-mediated actions of hemostatic proteases is a strategy that may be used to treat inflammatory disease without the bleeding complications of conventional anticoagulant therapies. The mechanisms by which proteases of the coagulant and fibrinolytic systems contribute to extravascular inflammation in disease will be considered in this review.

  2. Novel Treatment of Staphylococcus aureus Device-Related Infections Using Fibrinolytic Agents.

    Science.gov (United States)

    Hogan, S; O'Gara, J P; O'Neill, E

    2018-02-01

    Staphylococcal infections involving biofilms represent a significant challenge in the treatment of patients with device-related infections. Staphylococcus aureus biofilms have been shown to be SaeRS regulated and dependent on the coagulase-catalyzed conversion of fibrinogen into fibrin on surfaces coated with human plasma. Here we investigated the treatment of staphylococcal biofilm device-related infections by digesting the fibrin biofilm matrix with and without existing antimicrobials. The fibrinolytic agents plasmin, streptokinase, and nattokinase, and TrypLE, a recombinant trypsin-like protease, were used to digest and treat S. aureus biofilms grown in vitro using in vivo -like static biofilm assays with and without antimicrobials. Cytotoxicity, the potential to induce a cytokine response in whole human blood, and the risk of induction of tolerance to fibrinolytic agents were investigated. A rat model of intravascular catheter infection was established to investigate the efficacy of selected fibrinolytic agents in vivo Under biomimetic conditions, the fibrinolytic agents effectively dispersed established S. aureus biofilms and, in combination with common antistaphylococcal antimicrobials, effectively killed bacterial cells being released from the biofilm. These fibrinolytic agents were not cytotoxic and did not affect the host immune response. The rat model of infection successfully demonstrated the activity of the selected fibrinolytic agents alone and in combination with antimicrobials on established biofilms in vivo TrypLE and nattokinase most successfully removed adherent cells from plasma-coated surfaces and significantly improved the efficacy of existing antimicrobials against S. aureus biofilms in vitro and in vivo These biofilm dispersal agents represent a viable future treatment option for S. aureus device-related infections. Copyright © 2018 American Society for Microbiology.

  3. Evidence for an enduring ischaemic penumbra following central retinal artery occlusion, with implications for fibrinolytic therapy.

    Science.gov (United States)

    McLeod, David; Beatty, Stephen

    2015-11-01

    The rationale behind hyperacute fibrinolytic therapy for cerebral and retinal arterial occlusion is to rescue ischaemic cells from irreversible damage through timely restitution of tissue perfusion. In cerebral stroke, an anoxic tissue compartment (the "infarct core") is surrounded by a hypoxic compartment (the "ischaemic penumbra"). The latter comprises electrically-silent neurons that undergo delayed apoptotic cell death within 1-6 h unless salvaged by arterial recanalisation. Establishment of an equivalent hypoxic compartment within the inner retina following central retinal artery occlusion (CRAO) isn't widely acknowledged. During experimental CRAO, electroretinography reveals 3 oxygenation-based tissue compartments (anoxic, hypoxic and normoxic) that contribute 32%, 27% and 41% respectively to the pre-occlusion b-wave amplitude. Thus, once the anoxia survival time (≈2 h) expires, the contribution from the infarcted posterior retina is irreversibly extinguished, but electrical activity continues in the normoxic periphery. Inbetween these compartments, an annular hypoxic zone (the "penumbra obscura") endures in a structurally-intact but functionally-impaired state until retinal reperfusion allows rapid recovery from electrical silence. Clinically, residual circulation of sufficient volume flow rate generates the heterogeneous fundus picture of "partial" CRAO. Persistent retinal venous hypoxaemia signifies maximal extraction of oxygen by an enduring "polar penumbra" that permeates or largely replaces the infarct core. On retinal reperfusion some days later, the retinal venous oxygen saturation reverts to normal and vision improves. Thus, penumbral inner retina, marginally oxygenated by the choroid or by residual circulation, isn't at risk of delayed apoptotic infarction (unlike hypoxic cerebral cortex). Emergency fibrinolytic intervention is inappropriate, therefore, once the duration of CRAO exceeds 2 h. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Purification and Characterization of Fibrinolytic Proteases from Mushroom Volvariela volvaceae Extract.

    Directory of Open Access Journals (Sweden)

    Willy Praira

    2010-11-01

    Full Text Available Purification and Characterization of Fibrinolytic Proteases from Mushroom Volvariela volvaceae Extract. Ediblestraw mushroom (V. volvaceae has been known used for improvement of blood circulation due to its fibrinolyticcontent. The objective of the study is to purify and characterize fibrinolytic protease from straw mushroom extract.Purification were performed through several steps, i.e. precipitation using ammonium sulphate 75%, dialyzed membran(cut-off 10 kDa, and ion-exchange chromatography using DEAE Sepharose. The active fraction of DEAE-Sepharosecontains two purified protein bands with molecular weight of 12.9 and 15.8 kDa. The active fraction has specificactivity of 0.383 U/mg with 2.7 fold higher purification compared to its crude extract. Both crude and purified enzymeshad optimum activity at temperature of 50 ºC and pH 7 in 10 minutes of incubation. Fibrin zymographic profiledemonstrated that the enzyme hydrolyzed fibrin, as well as casein, indicating their potent fibrinolytic activity. Theenzyme was strongly inhibited by phenilmethylsulphonyl fluoride and N-p-tosil-L-lysinchloromethyl keton. Thissuggested that it was a serine protease. In summary, these results showed that crude and purified protease of strawmushroom (V. volvaceae has fibrinolytic activities that can be applied for alternative thrombolytic therapy.

  5. Purification and characterization of a fibrinolytic enzyme from tempeh bongkrek as an alternative of thrombolytic agents

    Science.gov (United States)

    Sasmita, I. R. A.; Sutrisno, A.; Zubaidah, E.; Wardani, A. K.

    2018-03-01

    Tempeh is one of Indonesia’s traditional foods that contain fibrinolytic enzymes. Tempeh bongkrek shows very strong activity among various tempeh. The fibrinolytic enzymes of bongkrek tempeh are obtained by steps of purification i.e, ammonium sulphate precipitation, ion exchange chromatography and gel filtration chromatography. The fibrinolytic enzymes has been successfully purified with a yield of 4.37%, specific activity of 3,361 U / mg and purification fold of 44.02. SDS PAGE analysis showed that the enzyme was purified in to single band with estimated molecular mass of 75.82 kDa. The purified enzyme has optimum pH of 7 and optimum temperature of 50°C and pH stability between pH 4 - 7 with temperature stability from 30°-50°C. The fibrinolytic activity is increased with addition of CaCl2 but inhibited with CuSO4, phenylmethylsulfonyl fluoride (PMSF), sodium dodecyl sulfate (SDS), and ethylenediaminetetraacetic acid (EDTA).

  6. Positive impact of hormone replacement therapy on the fibrinolytic system

    DEFF Research Database (Denmark)

    Madsen, J S; Kristensen, S R; Gram, J

    2003-01-01

    be of importance. OBJECTIVES: To investigate the prolonged effect of HRT on the fibrinolytic system and to determine whether two common polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) genes modulate this effect. Methods: Healthy postmenopausal women (n...... = 248) were randomized to HRT (n = 122) or no substitution (n = 126) 5 years prior to investigation. RESULTS: Significantly higher values of t-PA activity and lower values of PAI-1 activity and PAI-1 antigen were found in the HRT group compared with the control group. This effect was independent...... of smoking and without influence from the two common polymorphisms PAI-1 -675(4G/5G) and t-PA intron8ins311. Furthermore, no difference between opposed estrogen (with norethisterone acetate as the gestagen component) and unopposed estrogen therapy was found. Both an intention-to-treat and a per...

  7. High-pressure tolerance of earthworm fibrinolytic and digestive enzymes.

    Science.gov (United States)

    Akazawa, Shin-Ichi; Tokuyama, Haruka; Sato, Shunsuke; Watanabe, Toshinori; Shida, Yosuke; Ogasawara, Wataru

    2018-02-01

    Earthworms contain several digestive and therapeutic enzymes that are beneficial to our health and useful for biomass utilization. Specifically, earthworms contain potent fibrinolytic enzymes called lumbrokinases, which are highly stable even at room temperature and remain active in dried earthworm powder. However, the high-temperature sterilization method leads to the inactivation of enzymes. Therefore, we investigated the effect of high-pressure treatment (HPT) (from 0.1 MPa to 500 MPa at 25°C and 50°C) on the enzymatic activity of lumbrokinase (LK), α-amylase (AMY), endoglucanase (EG), β-glucosidase (BGL), and lipase (LP) of the earthworm Eisenia fetida, Waki strain, and its sterilization ability in producing dietary supplement. LK showed thermo- and high-pressure tolerance. In addition, HPT may have resulted in pressure-induced stabilization and activation of LK. Although AMY activity was maintained up to 400 MPa at 25°C, the apparent activity decreased slightly at 50°C with HPT. EG showed almost the same pattern as AMY. However, it is possible that the effects of temperature and pressure compensated each other under 100 MPa at 50°C. BGL was shown to be a pressure- and temperature-sensitive enzyme, and LP showed a thermo- and high-pressure tolerance. The slight decrease in apparent activity occurred under 200 MPa at both temperatures. Furthermore, the low-temperature and pressure treatment completely sterilized the samples. These results provide a basis for the development of a novel earthworm dietary supplement with fibrinolytic and digestive activity and of high-pressure-tolerant enzymes to be used for biomass pretreatment. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  8. Fibrinolytic response to tumor necrosis factor in healthy subjects

    NARCIS (Netherlands)

    van der Poll, T.; Levi, M. [=Marcel M.; Büller, H. R.; van Deventer, S. J.; de Boer, J. P.; Hack, C. E.; ten Cate, J. W.

    1991-01-01

    Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men,

  9. Influence of PAI-1 gene promoter-675 (4G/5G) polymorphism on fibrinolytic activity after cardiac surgery employing cardiopulmonary bypass.

    Science.gov (United States)

    Ozolina, Agnese; Strike, Eva; Jaunalksne, Inta; Serova, Jelena; Romanova, Tatjana; Zake, Liene Nikitina; Sabelnikovs, Olegs; Vanags, Indulis

    2012-01-01

    The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis.

  10. Haemorrheologic and fibrinolytic activities in pregnant women ...

    African Journals Online (AJOL)

    Packed cell volumes (PCV), relative whole blood viscosity (RWBV), relative plasma viscosity (RPV), plasma fibrinogen concentration (PFC), euglobulin lysis time (ELT), total proteins and albumin were estimated. The differences in the values of PCV, RWBV, RPV, PFC, total proteins, albumin and globulin with gestational age ...

  11. Purification and Characterisation of a Fibrinolytic Enzyme from Rhizopus micro sporus var. tuberosus

    Directory of Open Access Journals (Sweden)

    Shuli Zhang

    2015-01-01

    Full Text Available Extracellular fibrinolytic enzyme from Rhizopus microsporus var. tuberosus was purified and characterised. The microorganism was isolated in a distillery from daqu, a fermentative agent used in the production of Chinese liquor and vinegar at diff erent temperatures. The fibrinolytic enzyme was partially purifi ed by ammonium sulphate precipitation, dialysis, DEAE Sepharose® Fast Flow ion exchange chromatography and Sephadex G-75 gel filtration chromatography. The molecular mass of the fi brinolytic enzyme was estimated to be 24.5 kDa by SDS-PAGE. The purified enzyme showed optimal activity at pH=7.0 and 37 °C by fibrin plate method. It showed stronger resistance to the inhibition by trypsin and was stable at 37 °C retaining 96.1 % residual activity aft er 4 h of incubation. The fibrinolytic activity of the enzyme was enhanced by Na+, Ca2+, Mg2+ and Mn2+. Conversely, Zn2+ and Cu2+ partly inhibited enzymatic activity. Using fibrin plate method, we found that the enzyme not only degrades fibrin directly, but also activates plasminogen into plasmin to degrade fibrin. The results indicate that the pure enzyme has a potential in dissolving blood clot, and the possibility for application in the treatment of thrombosis.

  12. The peritoneal fibrinolytic response to conventional and laparoscopic colonic surgery

    NARCIS (Netherlands)

    Brokelman, Walter; Holmdahl, Lena; Falk, Peter; Klinkenbijl, Jean; Reijnen, Michel

    2009-01-01

    Laparoscopic surgery is considered to induce less peritoneal trauma than conventional surgery. The peritoneal plasmin system is important in the processes of peritoneal healing and adhesion formation. The present study assessed the peritoneal fibrinolytic response to laparoscopic and conventional

  13. A role for the fibrinolytic system in postsurgical adhesion formation

    NARCIS (Netherlands)

    Hellebrekers, Bart W. J.; Emeis, Jef J.; Kooistra, Teake; Trimbos, J. Baptist; Moore, Norma R.; Zwinderman, Koos H.; Trimbos-Kemper, Trudy C. M.

    2005-01-01

    To look for evidence of a fibrinolytic insufficiency as a cause of adhesion formation. Retrospective and prospective study. University medical center. Retrospective study: 50 patients undergoing laparoscopy, divided into patients with and without endometriosis. Prospective study: 18 patients

  14. Purification, biochemical, and structural characterization of a novel fibrinolytic enzyme from Mucor subtilissimus UCP 1262.

    Science.gov (United States)

    Nascimento, Thiago Pajeú; Sales, Amanda Emmanuelle; Porto, Tatiana Souza; Costa, Romero Marcos Pedrosa Brandão; Breydo, Leonid; Uversky, Vladimir N; Porto, Ana Lúcia Figueiredo; Converti, Attilio

    2017-08-01

    Fibrinolytic proteases are enzymes that degrade fibrin. They provide a promising alternative to existing drugs for thrombolytic therapy. A protease isolated from the filamentous fungus Mucor subtilissimus UCP 1262 was purified in three steps by ammonium sulfate fractionation, ion exchange, and molecular exclusion chromatographies, and characterized biochemically and structurally. The purified protease exhibited a molecular mass of 20 kDa, an apparent isoelectric point of 4.94 and a secondary structure composed mainly of α-helices. Selectivity for N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as substrate suggests that this enzyme is a chymotrypsin-like serine protease, whose activity was enhanced by the addition of Cu 2+ , Mg 2+ , and Fe 2+ . The enzyme showed a fibrinolytic activity of 22.53 U/mL at 40 °C and its contact with polyethylene glycol did not lead to any significant alteration of its secondary structure. This protein represents an important example of a novel fibrinolytic enzyme with potential use in the treatment of thromboembolic disorders such as strokes, pulmonary emboli, and deep vein thrombosis.

  15. Role of altered coagulation-fibrinolytic system in the pathophysiology of diabetic retinopathy.

    Science.gov (United States)

    Behl, Tapan; Velpandian, Thirumurthy; Kotwani, Anita

    2017-05-01

    The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been well researched upon and established. However, its role in the progression of diabetic retinopathy has not been explored much. Since a decade, it is known that hyperglycemia is associated with a hypercoagulated state and the various impairments it causes are well acknowledged as independent risk factors for the development of cardiovascular diseases. But recent studies suggest that the hypercoagulative state and diminished fibrinolytic responses might also alter retinal homeostasis and induce several deleterious molecular changes in retinal cells which aggravate the already existing hyperglycemia-induced pathological conditions and thereby lead to the progression of diabetic retinopathy. The major mediators of coagulation-fibrinolytic system whose concentration or activity get altered during hyperglycemia include fibrinogen, antithrombin-III (AT-III), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). Inhibiting the pathways by which these altered mediators get involved in the pathophysiology of diabetic retinopathy can serve as potential targets for the development of an adjuvant novel alternative therapy for diabetic retinopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Beneficial effect of a moderately energy-restricted diet on fibrinolytic factors in non-obese men

    NARCIS (Netherlands)

    Velthuis-te Wierik, E.J.M.; Meijer, P.; Kluft, C.; Berg, H. van den

    1995-01-01

    Impaired fibrinolytic activity has been reported in the elderly and is thought to play a role in the etiology of cardiovascular disease, one of the leading causes of death in most Western countries. Since restriction of energy intake has been demonstrated to act beneficially on the aging process in

  17. Thrombolytic effects of Douchi Fibrinolytic enzyme from Bacillus subtilis LD-8547 in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Yuan Jun

    2012-07-01

    Full Text Available Abstract Background Today, thrombosis is one of the most widely occurring diseases in modern life. Drugs with thrombolytic functions are the most effective methods in the treatment of thrombosis. Among them, Douchi fibrinolytic enzyme (DFE is a promising agent. DFE was isolated from Douchi, a typical and popular soybean-fermented food in China, and it can dissolve fibrin directly and efficiently. A strain, Bacillus subtilis LD-8547 produced DFE with high fibrinolytic activity has been isolated in our lab previously. Results In the study, thrombolytic effect of DFE from Bacillus subtilis LD-8547 was studied in vitro and in vivo systematically. The results showed that DFE played a significant role in thrombolysis and anticoagulation in vitro. And the thrombolytic effects correlated with DFE in a dose-dependent manner. In vivo, the acute toxicity assay showed that DFE had no obvious acute toxicity to mice. Test of carrageenan-induced thrombosis in mice indicated that the DFE significantly prevented tail thrombosis, and arterial thrombosis model test indicated that Douchi fibrinolytic enzyme DFE had thrombolytic effect on carotid thrombosis of rabbits in vivo. Other results in vivo indicated that DFE could increase bleeding and clotting time obviously. Conclusions The DFE isolated from Bacillus subtilis LD-8547 has obvious thrombolytic effects in vitro and in vivo. This function demonstrates that this enzyme can be a useful tool for preventing and treating clinical thrombus.

  18. Fibrinolytic dysfunction in insulin-resistant women with previous gestational diabetes.

    Science.gov (United States)

    Farhan, S; Winzer, C; Tura, A; Quehenberger, P; Bieglmaier, C; Wagner, O F; Huber, K; Waldhäusl, W; Pacini, G; Kautzky-Willer, A

    2006-05-01

    Women with a history of gestational diabetes (p-GDM) are at increased risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at increased risk for future cardiovascular disease. Three months after delivery we investigated the plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (t-PA), fibrinogen and von Willebrand factor (vWF) in 74 women with p-GDM and 20 healthy females with normal glucose tolerance during and after pregnancy, as well as the relation of fibrinolytic parameters to insulin resistance and glycaemic control. All women underwent an oral (OGTT) as well as an intravenous glucose tolerance test (FSIGT). Mathematical model analysis disclosed that 50% (n=37 each) of the p-GDM subjects had normal (NIS) or impaired (IIS) insulin sensitivity. Parameters of interest were determined using commercially available test systems. Women with p-GDM and IIS had significantly increased body fat mass (BFM) (Pwomen with p-GDM and NIS and controls, whereas the waist to hip ratio (WHR) was similar in both p-GDM groups but was higher compared with the controls (Pwomen with p-GDM and IIS compared with women with p-GDM and NIS and the controls (Pwomen with IIS had higher PAI-1 levels than lean women with IIS (Pwomen with IIS (Pwomen with IIS independently of their glucose tolerance status (Pwomen with IIS and depends on plasma proinsulin and abdominal obesity. An increase of the PAI-1/SI ratio further characterizes obese insulin-resistant p-GDM women who may be at risk for diabetes and angiopathy.

  19. Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models

    Science.gov (United States)

    Florova, Galina; Azghani, Ali O.; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M.; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

    2016-01-01

    The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP. PMID:27343192

  20. Time to fibrinolytics for acute myocardial infarction: Reasons for ...

    African Journals Online (AJOL)

    The cornerstone of STEMI management is early re vascularisation, either by primary percutaneous coronary intervention or fibrinolytic therapy, in conjunction with other adjunctive pharmaceutical agents.[1] The most important determinant of outcome, irrespective of which form of revascularisation is selected, is the time from ...

  1. Time to fibrinolytics for acute myocardial infarction: Reasons for ...

    African Journals Online (AJOL)

    The median time delays from onset of symptoms to call for help, between calling for help and arriving at hospital, and from hospital arrival to fibrinolytic agent administration, were 35 minutes (5 - 1 185), 55 minutes (12.5 - 670) and 62.5 minutes (16.5 - 282), respectively. Numerous delays were identified at all stages, with ...

  2. Time to fibrinolytics for acute myocardial infarction: Reasons for ...

    African Journals Online (AJOL)

    reperfusion strategy for STEMI is primary percutaneous coronary intervention ... of any reperfusion strategy, including fibrinolytic therapy, to patients presenting with ... Data in respect of demographics, timing ... being non-cardiac in nature. ..... Recognition of the seriousness and extent of this disease ... Infarction Audit Group.

  3. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors

    NARCIS (Netherlands)

    Stuijver, Danka J. F.; van Zaane, Bregje; Romualdi, Erica; Brandjes, Dees P. M.; Gerdes, Victor E. A.; Squizzato, Alessandro

    2012-01-01

    Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis

  4. EFFECT OF RECOMBINANT TISSUE-PLASMINOGEN ACTIVATOR ON INTRAABDOMINAL ABSCESS FORMATION IN RATS WITH GENERALIZED PERITONITIS

    NARCIS (Netherlands)

    van Goor, Harry; de Graaf, JS; Kooi, K; Sluiter, WJ; Bom, VJJ; van der Meer, J; Bleichrodt, RP

    1994-01-01

    BACKGROUND: During generalized peritonitis, intraabdominal fibrin deposition is stimulated whereas fibrinolytic activity is reduced, which predisposes intra-abdominal abscess formation. We investigated the effects of increasing the intra-abdominal fibrinolytic activity on abscess formation by

  5. Purification and Antithrombotic Potential of a Fibrinolytic Enzyme from Shiitake Culinary- Medicinal Mushroom, Lentinus edodes GNA01 (Agaricomycetes).

    Science.gov (United States)

    Choi, Jun-Hui; Kim, Kyung-Je; Kim, Seung

    2018-01-01

    We purified Lentinus edodes GNA01 fibrinolytic enzyme (LEFE) and identified it as a novel metalloprotease. LEFE was purified to homogeneity through a 2-step procedure, with an 8.28-fold increase in specific activity and 5.3% recovery. The molecular mass of LEFE was approximately 38 kDa, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Its optimal pH, optimal temperature, pH stability, and thermal stability were 5, 30°C, 6-7, and 40°C, respectively. LEFE was inhibited by zinc and magnesium ions, and by EDTA and EGTA, indicating that LEFE is a metalloprotease. The protease exhibited fibrinolytic activity and a degradative effect on clot formation and blood clots. The protease prolonged activated partial thromboplastin time, prothrombin time, and coagulation time as induced by platelet aggregators (collagen and epinephrine). Taken together, our results indicate that L. edodes GNA01 produces a metalloprotease/fibrinolytic enzyme and that this enzyme might be applied as a new thrombolytic and antithrombotic agent for thrombosis-related cardiovascular disorders.

  6. Purification and characterization of a fibrinolytic enzyme produced from Bacillus sp. strain CK 11-4 screened from Chungkook-Jang.

    Science.gov (United States)

    Kim, W; Choi, K; Kim, Y; Park, H; Choi, J; Lee, Y; Oh, H; Kwon, I; Lee, S

    1996-01-01

    Bacillus sp. strain CK 11-4, which produces a strongly fibrinolytic enzyme, was screened from Chungkook-Jang, a traditional Korean fermented-soybean sauce. The fibrinolytic enzyme (CK) was purified from supernatant of Bacillus sp. strain CK 11-4 culture broth and showed thermophilic, hydrophilic, and strong fibrinolytic activity. The optimum temperature and pH were 70 degrees C and 10.5, respectively, and the molecular weight was 28,200 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The first 14 amino acids of the N-terminal sequence of CK are Ala-Gin-Thr-Val-Pro-Tyr-Gly-Ile-Pro-Leu-Ile-Lys-Ala-Asp. This sequence is identical to that of subtilisin Carlsberg and different from that of nattokinase, but CK showed a level of fibrinolytic activity that was about eight times higher than that of subtilisin Carlsberg. The amidolytic activity of CK increased about twofold at the initial state of the reaction when CK enzyme was added to a mixture of plasminogen and substrate (H-D-Val-Leu-Lys-pNA). A similar result was also obtained from fibrin plate analysis. PMID:8779587

  7. An Experiential Learning Activity Demonstrating Normal and Phobic Anxiety

    Science.gov (United States)

    Canu, Will H.

    2008-01-01

    This article describes an activity for an undergraduate abnormal psychology course that used student-generated data to illustrate normal versus clinically significant anxiety responses related to specific phobias. Students (N = 37) viewed 14 images of low- or high-anxiety valence and rated their subjective response to each. Discussion in a…

  8. Analysis of promoter activity in transgenic plants by normalizing ...

    Indian Academy of Sciences (India)

    Analysis of promoter activity in transgenic plants by normalizing expression with a reference gene: anomalies due to the influence of the test promoter on the reference promoter. Simran Bhullar Suma Chakravarthy Deepak Pental Pradeep Kumar Burma. Articles Volume 34 Issue 6 December 2009 pp 953-962 ...

  9. Plasma renin activity profile in normal and hypertensive Filipinos

    International Nuclear Information System (INIS)

    Guevara, R.; Torres, J. Jr.; Abundo, H.P.; Perez, A.P.

    To establish a base line profile of plasma renin activity in normotensive and hypertensive Filipinos, 1.019 cases, 479 males and 540 females with an age range 14 - 89 years (mean - 46 + -20) were studied at the Santo Tomas University Hospital of various life styles from the Metro-Manila area, 248 comprised the normotensive group (male - 122 or 49.2 %, female 126 or 50.8 %) and 771 were hypertensive. Of these, 711 (92.6 %) has essential hypertension and are presented in this report. Plasma Renin Activity was determined by radioimmunoassay using Dainabot Renin-Ricket. Concurrent 24 hr. urine sodium and potassium were determined. Nomograms of plasma renin activity as related to urine sodium excretion were drawn after computerized statistical analysis of data. The normal mean value of plasma renin activity was found to be 1.64 + - 0.81 ng./ml./hr. in the upright position and 1.15 + - .68 ng./ml./hr. in the supine position. Based on the nomogram derived, the values obtained in the 711 cases of essential hypertension were classified into High Renin - 14.3 % Normal Renin - 56.1 % and Low Renin - 29.6 %. This study establishes normal levels of plasma renin activity as well as define and classify same renin activity among hypertensive Filipinos, a useful and practicable guide for treatment and can be of prognostic significance. (author)

  10. Local fibrinolytic therapy for patients with cerebral embolism and reversibility of cerebral ischemia in ultra-acute stage

    International Nuclear Information System (INIS)

    Koizumi, Takayuki

    1993-01-01

    The present study was undertaken to determine candidates for fibrinolytic therapy in cerebral embolism. Forty-three patients were examined by single photon emission computed tomography (SPECT) using 99m c-d, hexamethyl-propylene-amine oxime (HM-PAO) or N-isopropyl p[ 123 I]-iodoamphetamine ( 123 I-IMP) just before and after intra-arterial local fibrinolytic therapy. Regional cerebellar ratio (R/Ce) and asymmetry index (AI) were calculated just before the treatment (n=9). Quantitative analysis was performed after the treatment (n=all). SPECT images taken within 24 hours after the treatment fell into three patters: normal perfusion, hypoperfusion, and hyperperfusion. Patients showing normal perfusion pattern after complete recanalization developed no or smaller infarction on CT scans. However, patients showing either hypoperfusion or hyperperfusion developed large infarction. Regions with R/Ce ratio of 0.3 or smaller and/or AI of 1.5 or greater were irreversible, which was associated with cerebral infarction regardless of the duration of ischemia. On the other hand, regions with R/Ce of 0.5 or greater or AI of 1.2 or smaller were reversible with no association of infarction. Intra-arterial local fibrinolytic therapy seems to be helpful for patients with slight reduction of regional cerebral blood flow (i.e., R/Ce>0.5, AI 1.5). These findings indicate that SPECT is capable of determining reversibility of ischemic region, thereby contributing to better management of patients with acute cerebral embolism. (N.K.)

  11. Discrepant fibrinolytic response in plasma and whole blood during experimental endotoxemia in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Sisse R Ostrowski

    Full Text Available Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG.Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour, with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest were recorded. Mixed models with Tukey post hoc tests and correlations were applied.Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05. Platelet aggregation decreased (all tests, p<0.05, whereas TEG whole blood clot firmness increased (G, p = 0.05. Furthermore, during endotoxemia (4 h, whole blood fibrinolysis increased (clot lysis time (CLT, p<0.001 and Functional Fibrinogen clot strength decreased (p = 0.049. After endotoxemia (6 h, whole blood fibrinolysis was reduced (CLT, p<0.05. In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001.Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are

  12. Muscle activity and inactivity periods during normal daily life.

    Directory of Open Access Journals (Sweden)

    Olli Tikkanen

    Full Text Available Recent findings suggest that not only the lack of physical activity, but also prolonged times of sedentary behaviour where major locomotor muscles are inactive, significantly increase the risk of chronic diseases. The purpose of this study was to provide details of quadriceps and hamstring muscle inactivity and activity during normal daily life of ordinary people. Eighty-four volunteers (44 females, 40 males, 44.1±17.3 years, 172.3±6.1 cm, 70.1±10.2 kg were measured during normal daily life using shorts measuring muscle electromyographic (EMG activity (recording time 11.3±2.0 hours. EMG was normalized to isometric MVC (EMG(MVC during knee flexion and extension, and inactivity threshold of each muscle group was defined as 90% of EMG activity during standing (2.5±1.7% of EMG(MVC. During normal daily life the average EMG amplitude was 4.0±2.6% and average activity burst amplitude was 5.8±3.4% of EMG(MVC (mean duration of 1.4±1.4 s which is below the EMG level required for walking (5 km/h corresponding to EMG level of about 10% of EMG(MVC. Using the proposed individual inactivity threshold, thigh muscles were inactive 67.5±11.9% of the total recording time and the longest inactivity periods lasted for 13.9±7.3 min (2.5-38.3 min. Women had more activity bursts and spent more time at intensities above 40% EMG(MVC than men (p<0.05. In conclusion, during normal daily life the locomotor muscles are inactive about 7.5 hours, and only a small fraction of muscle's maximal voluntary activation capacity is used averaging only 4% of the maximal recruitment of the thigh muscles. Some daily non-exercise activities such as stair climbing produce much higher muscle activity levels than brisk walking, and replacing sitting by standing can considerably increase cumulative daily muscle activity.

  13. Super Normal Vector for Human Activity Recognition with Depth Cameras.

    Science.gov (United States)

    Yang, Xiaodong; Tian, YingLi

    2017-05-01

    The advent of cost-effectiveness and easy-operation depth cameras has facilitated a variety of visual recognition tasks including human activity recognition. This paper presents a novel framework for recognizing human activities from video sequences captured by depth cameras. We extend the surface normal to polynormal by assembling local neighboring hypersurface normals from a depth sequence to jointly characterize local motion and shape information. We then propose a general scheme of super normal vector (SNV) to aggregate the low-level polynormals into a discriminative representation, which can be viewed as a simplified version of the Fisher kernel representation. In order to globally capture the spatial layout and temporal order, an adaptive spatio-temporal pyramid is introduced to subdivide a depth video into a set of space-time cells. In the extensive experiments, the proposed approach achieves superior performance to the state-of-the-art methods on the four public benchmark datasets, i.e., MSRAction3D, MSRDailyActivity3D, MSRGesture3D, and MSRActionPairs3D.

  14. Production, purification and characterization of fibrinolytic enzyme from Serratia sp. KG-2-1 using optimized media.

    Science.gov (United States)

    Taneja, Kapila; Bajaj, Bijender Kumar; Kumar, Sandeep; Dilbaghi, Neeraj

    2017-07-01

    Intravascular thrombosis is one of the major causes of variety of cardiovascular disorders leading to high mortality worldwide. Fibrinolytic enzymes from microbial sources possess ability to dissolve these clots and help to circumvent these problems in more efficient and safer way. In the present study, fibrinolytic protease with higher fibrinolytic activity than plasmin was obtained from Serratia sp. KG-2-1 isolated from garbage dump soil. Response surface methodology was used to study the interactive effect of concentration of maltose, yeast extract + peptone (1:1), incubation time, and pH on enzyme production and biomass. Maximum enzyme production was achieved at 33 °C after 24 h at neutral pH in media containing 1.5% Maltose, 4.0% yeast extract + peptone and other trace elements resulting in 1.82 folds increased production. The enzyme was purified from crude extract using ammonium sulfate precipitation and DEAE-Sephadex chromatography resulting in 12.9 fold purification with 14.9% yield. The purified enzyme belongs to metalloprotease class and had optimal activity in conditions similar to physiological environment with temperature optima of 40 °C and pH optima of 8. The enzyme was found to be stable in various solvents and its activity was enhanced in presence of Na + , K + , Ba 2+ , Cu 2+ , Mn 2+ , Hg 2+ but inhibited by Ca 2+ and Fe 3+ . Hence, the obtained enzyme may be used as potential therapeutic agent in combating various thrombolytic disorders.

  15. The experimental investigation of fibrinolytic system under the influence of flocalin in conditions of acute hypoxic kidney injury

    Directory of Open Access Journals (Sweden)

    A. I. Gozhenko

    2017-08-01

    Full Text Available In the experiments on rats subjected to acute hypoxic histochemical nephropathy, caused by sodium nitrite and 2,4-dinitrophenol, fibrinolytic activities of blood plasma, urine, renal cortex, medulla, and papilla after treatment with flocalin – the activator of KATP channels, were studied­. It was shown that in the conditions of acute kidney hypoxic injury flocalin administration resulted in the increase and essential restoration of fibrinolysis in blood plasma diminished under hypoxia, which was due to the growth of non-enzymatic fibrinolysis, whereas in urine and renal medulla the appreciable increase of enzymatic fibrinolytic activity took place. Moreover, the treatment of hypoxic nephropathy animals by flocalin resulted in the marked restoration of kidney ion regulatory and protein excretory functions that proves the positive influence of KATP channels activation on the one of the biochemical mechanisms of acute kidney injury as well as the protective effect of flocalin in relation to tubular cells of nephron. The obtained results testify to the beneficial effects of KATP channels activation in the conditions of acute hypoxic kidneys injury.

  16. Purification and characterization of a strong fibrinolytic enzyme (nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan.

    Science.gov (United States)

    Fujita, M; Nomura, K; Hong, K; Ito, Y; Asada, A; Nishimuro, S

    1993-12-30

    A strong fibrinolytic enzyme (nattokinase) was purified from the vegetable cheese natto. Nattokinase was extracted from natto with saline and isolated by sequential use of hydrophobic chromatography on Butyl-Toyopearl, ion-exchange chromatography on CM-Toyopearl, and gel-filtration on Sephadex G-50. The isolated protein gave a single sharp band on SDS-PAGE either before or after reduction. The sequence, as determined by automated Edman degradation of the uncleaved molecule and its enzymatically derived peptide, consisted of a total 275 amino acid residues (M.W = 27,728) and exhibited a high homology with the subtilisins. The purified nattokinase digested not only fibrin but also several synthetic substrates. Among the synthetic substrates, the most sensitive substrate was Suc-Ala-Ala-Pro-Phe-pNA for subtilisin. PMSF inhibited both the fibrinolytic activity and the amidolytic activity. The results indicate that nattokinase is a subtilisin-like serine protease.

  17. Intra week reliability of Fibrinolytic and metabolic parameters and stability of their covariance structure

    NARCIS (Netherlands)

    Riese, H.; Vrijkotte, T.; Meijer, P.; Kluft, C.; Geus, E. de

    1999-01-01

    Interactions between lipoproteins and fibrinolytic parameters inducing cardiovascular disease are gradually being disclosed. The multivariate analyses often used in studies investigating this relationship implicitly assume 1) that the reliability of the parameters in a cluster is comparably high,

  18. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

    Science.gov (United States)

    Henry, David A; Carless, Paul A; Moxey, Annette J; O’Connell, Dianne; Stokes, Barrie J; Fergusson, Dean A; Ker, Katharine

    2014-01-01

    Background Concerns regarding the safety of transfused blood have led to the development of a range of interventions to minimise blood loss during major surgery. Anti-fibrinolytic drugs are widely used, particularly in cardiac surgery, and previous reviews have found them to be effective in reducing blood loss, the need for transfusion, and the need for re-operation due to continued or recurrent bleeding. In the last few years questions have been raised regarding the comparative performance of the drugs. The safety of the most popular agent, aprotinin, has been challenged, and it was withdrawn from world markets in May 2008 because of concerns that it increased the risk of cardiovascular complications and death. Objectives To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood cell (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death. Search methods We searched: the Cochrane Injuries Group’s Specialised Register (July 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (Ovid SP) 1950 to July 2010, EMBASE (Ovid SP) 1980 to July 2010. References in identified trials and review articles were checked and trial authors were contacted to identify any additional studies. The searches were last updated in July 2010. Selection criteria Randomised controlled trials (RCTs) of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Eligible trials compared anti-fibrinolytic drugs with placebo (or no treatment), or with each other. Data collection and analysis Two authors independently assessed trial quality and extracted data. This version of the review includes a sensitivity analysis excluding trials authored by Prof. Joachim Boldt. Main results This review summarises data from 252 RCTs that recruited over 25,000 participants. Data from

  19. Haemorrheologic and fibrinolytic activities in diabetics resident in ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-05-16

    May 16, 2008 ... INTRODUCTION. Diabetes .... Ugwu (1987) Ingram's and Hills (1976) and Nelson (1944) were .... McGraw Hill, pp. ... International committee communications. Reference methods for one stage prothrombin time test on human.

  20. Changes in Coagulation and Fibrinolytic Indices in Women with Polycystic Ovarian Syndrome Undergoing Controlled Ovarian Hyperstimulation

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2014-01-01

    Full Text Available Background. Polycystic ovarian syndrome (PCOS women undergoing in vitro fertilization and embryo transfer (IVF-ET treatment always attain a low cumulative pregnancy rate disaccording with the satisfactory number of oocytes. Objective. We aim to evaluate the status of coagulation and fibrinolytic system in PCOS patients undergoing controlled ovarian hyperstimulation (COH process. Method. Of the 97 women, 30 patients with PCOS composed the study group; 67 women of child-bearing age with normal endocrine function composed the control group. All participants underwent GnRH agonist standard long protocol, and plasma HCY, FVIII, FX, and D-dimer levels as well as hormone parameters were measured at day of full downregulation, hCG priming, and embryos transfer. Results. On day of full downregulation, FX levels were significantly higher in PCOS group (P<0.01. On hCG priming day, FX and estrogen levels in PCOS group were higher than in the control group and FVIII levels were significantly lower on day of embryos transfer whereas FX and E2 levels were significantly higher in PCOS group. Conclusion. Hypercoagulable state during peri-implantation phase would probably lead to poor microcirculation of endometrium and be one of the most important disadvantages of successful implantation and subsequent clinical pregnancy.

  1. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis.

    Science.gov (United States)

    Stuijver, Danka J F; van Zaane, Bregje; Romualdi, Erica; Brandjes, Dees P M; Gerdes, Victor E A; Squizzato, Alessandro

    2012-12-01

    Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.

  2. Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity.

    Science.gov (United States)

    Pais, Eszter; Alexy, Tamas; Holsworth, Ralph E; Meiselman, Herbert J

    2006-01-01

    The vegetable cheese-like food, natto, is extremely popular in Japan with a history extending back over 1000 years. A fibrinolytic enzyme, termed nattokinase, can be extracted from natto; the enzyme is a subtilisin-like serine protease composed of 275 amino acid residues and has a molecular weight of 27.7 kDa. In vitro and in vivo studies have consistently demonstrated the potent pro-fibrinolytic effect of the enzyme. However, no studies to date have evaluated the effects of nattokinase on various hemorheological parameters and thus we have begun to assess the effects of the enzyme on RBC aggregation and blood viscosity. Blood samples were incubated with nattokinase (final activities of 0, 15.6, 31.3, 62.5 and 125 units/ml) for 30 minutes at 37 degrees C. RBC aggregation was measured using a Myrenne MA-1 aggregometer and blood viscosity assessed over 1-1000 s(-1) with a computer controlled scanning capillary rheometer (Rheolog). Our in vitro results showed a significant, dose-dependent decrease of RBC aggregation and low-shear viscosity, with these beneficial effects evident at concentrations similar to those achieved in previous in vivo animal trials. Our preliminary data thus indicate positive in vitro hemorheological effects of nattokinase, and suggest its potential value as a therapeutic agent and the need for additional studies and clinical trials.

  3. Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson's Disease.

    Science.gov (United States)

    Harrington, Deborah L; Shen, Qian; Castillo, Gabriel N; Filoteo, J Vincent; Litvan, Irene; Takahashi, Colleen; French, Chelsea

    2017-01-01

    Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson's disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological

  4. Direct Fibrinolytic Snake Venom Metalloproteinases Affecting Hemostasis: Structural, Biochemical Features and Therapeutic Potential.

    Science.gov (United States)

    Sanchez, Eladio F; Flores-Ortiz, Renzo J; Alvarenga, Valeria G; Eble, Johannes A

    2017-12-05

    Snake venom metalloproteinases (SVMPs) are predominant in viperid venoms, which provoke hemorrhage and affect hemostasis and thrombosis. P-I class enzymes consist only of a single metalloproteinase domain. Despite sharing high sequence homology, only some of them induce hemorrhage. They have direct fibrin(ogen)olytic activity. Their main biological substrate is fibrin(ogen), whose Aα-chain is degraded rapidly and independently of activation of plasminogen. It is important to understand their biochemical and physiological mechanisms, as well as their applications, to study the etiology of some human diseases and to identify sites of potential intervention. As compared to all current antiplatelet therapies to treat cardiovascular events, the SVMPs have outstanding biochemical attributes: (a) they are insensitive to plasma serine proteinase inhibitors; (b) they have the potential to avoid bleeding risk; (c) mechanistically, they are inactivated/cleared by α2-macroglobulin that limits their range of action in circulation; and (d) few of them also impair platelet aggregation that represent an important target for therapeutic intervention. This review will briefly highlight the structure-function relationships of these few direct-acting fibrinolytic agents, including, barnettlysin-I, isolated from Bothrops barnetti venom, that could be considered as potential agent to treat major thrombotic disorders. Some of their pharmacological advantages are compared with plasmin.

  5. Direct Fibrinolytic Snake Venom Metalloproteinases Affecting Hemostasis: Structural, Biochemical Features and Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Eladio F. Sanchez

    2017-12-01

    Full Text Available Snake venom metalloproteinases (SVMPs are predominant in viperid venoms, which provoke hemorrhage and affect hemostasis and thrombosis. P-I class enzymes consist only of a single metalloproteinase domain. Despite sharing high sequence homology, only some of them induce hemorrhage. They have direct fibrin(ogenolytic activity. Their main biological substrate is fibrin(ogen, whose Aα-chain is degraded rapidly and independently of activation of plasminogen. It is important to understand their biochemical and physiological mechanisms, as well as their applications, to study the etiology of some human diseases and to identify sites of potential intervention. As compared to all current antiplatelet therapies to treat cardiovascular events, the SVMPs have outstanding biochemical attributes: (a they are insensitive to plasma serine proteinase inhibitors; (b they have the potential to avoid bleeding risk; (c mechanistically, they are inactivated/cleared by α2-macroglobulin that limits their range of action in circulation; and (d few of them also impair platelet aggregation that represent an important target for therapeutic intervention. This review will briefly highlight the structure–function relationships of these few direct-acting fibrinolytic agents, including, barnettlysin-I, isolated from Bothrops barnetti venom, that could be considered as potential agent to treat major thrombotic disorders. Some of their pharmacological advantages are compared with plasmin.

  6. Thrombin regulates components of the fibrinolytic system in human mesangial cells

    International Nuclear Information System (INIS)

    Villamediana, L.M.; Rondeau, E.; He, C.J.; Medcalf, R.L.; Peraldi, M.N.; Lacave, R.; Delarue, F.; Sraer, J.D.

    1990-01-01

    Besides its procoagulant activity, thrombin has been shown to stimulate cell proliferation and to regulate the fibrinolytic pathway. We report here the effect of purified human alpha thrombin on the synthesis of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) by cultured human mesangial cells. Thrombin (0 to 2.5 U/ml) increased in a time- and dose-dependent manner the production of t-PA and PAI-1 (2- to 3-fold increase of secreted t-PA and PAI-1 release during a 24 hour incubation). This effect was associated with a twofold increase in DNA synthesis measured by 3H-thymidine incorporation. Zymographic analysis and reverse fibrin autography showed that thrombin also increased the level of the 110 Kd t-PA-PAI-1 complex, whereas PAI-1 was present as a free 50 Kd form in the culture medium conditioned by unstimulated and thrombin-stimulated cells. Free t-PA was never observed. Both membrane binding and catalytic activity of thrombin were required since the effects of 1 U/ml thrombin were inhibited by addition 2 U/ml hirudin, which inhibits the membrane binding and catalytic activity of thrombin, and since DFP-inactivated thrombin, which has the ability to bind but which has no enzymatic activity, did not induce t-PA or PAI-1. Gamma thrombin, which does not bind to thrombin receptor, did not increase t-PA and PAI-1 releases. The effects of thrombin were probably mediated by protein kinase C activation since H7, an inhibitor of protein kinases, inhibited significantly thrombin effects on t-PA and PAI-1 production, and since addition of an activator of protein kinase A, 8-bromocyclic AMP (100 microM), induced a significant inhibition of the thrombin effect. The effects of thrombin were also suppressed by 1.25 micrograms/ml alpha amanitin, suggesting a requirement of de novo RNA synthesis

  7. Purification of a fibrinolytic protease from Mucor subtilissimus UCP 1262 by aqueous two-phase systems (PEG/sulfate).

    Science.gov (United States)

    Nascimento, Thiago Pajeú; Sales, Amanda Emmanuelle; Porto, Camila Souza; Brandão, Romero Marcos Pedrosa; de Campos-Takaki, Galba Maria; Teixeira, José Antônio Couto; Porto, Tatiana Souza; Porto, Ana Lúcia Figueiredo; Converti, Attilio

    2016-07-01

    A fibrinolytic protease from M. subtilissimus UCP 1262 was recovered and partially purified by polyethylene glycol (PEG)/sodium sulfate aqueous two-phase systems (ATPS). The simultaneous influence of PEG molar mass, PEG concentration and sulfate concentration on the enzyme recovery was first investigated using a 2(3) full factorial design, and the Response Surface Methodology used to identify the optimum conditions for enzyme extraction by ATPS. Once the best PEG molar mass for the process had been selected (6000g/mol), a two-factor central composite rotary design was applied to better evaluate the effects of the other two independent variables. The fibrinolytic enzyme was shown to preferentially partition to the bottom phase with a partition coefficient (K) ranging from 0.2 to 0.7. The best results in terms of enzyme purification were obtained with the system formed by 30.0% (w/w) PEG 6000g/mol and 13.2% (w/w) sodium sulfate, which ensured a purification factor of 10.0, K of 0.2 and activity yield of 102.0%. SDS-PAGE and fibrin zymography showed that the purified protease has a molecular mass of 97kDa and an apparent isoelectric point of 5.4. When submitted to assays with different substrates and inhibitors, it showed selectivity for succinyl-l-ala-ala-pro-l-phenylalanine-p-nitroanilide and was almost completely inhibited by phenylmethylsulfonyl fluoride, behaving as a chymotrypsin-like protease. At the optimum temperature of 37°C, the enzyme residual activity was 94 and 68% of the initial one after 120 and 150min of incubation, respectively. This study demonstrated that M. subtilissimus protease has potent fibrinolytic activity compared with similar enzymes produced by solid-state fermentation, therefore it may be used as an agent for the prevention and therapy of thrombosis. Furthermore, it appears to have the advantages of low cost production and simple purification. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Hypoglycemic Activity Of Polygala arvensis In Normal And Alloxan ...

    African Journals Online (AJOL)

    Blood glucose was estimated by the glucose oxidase method in both normal and alloxan-induced diabetic rats before and 2h after the administration of drugs. The glycogen content of the liver, skeletal muscle, cardiac muscle and glucose uptake by isolated rat hemi-diaphragm were estimated. It showed significant reduction ...

  9. A novel fibrinolytic metalloproteinase, barnettlysin-I from Bothrops barnetti (Barnett´s pitviper) snake venom with anti-platelet properties.

    Science.gov (United States)

    Sanchez, Eladio Flores; Richardson, Michael; Gremski, Luiza Helena; Veiga, Silvio Sanches; Yarleque, Armando; Niland, Stephan; Lima, Augusto Martins; Estevao-Costa, Maria Inácia; Eble, Johannes Andreas

    2016-03-01

    Viperid snake venoms contain active components that interfere with hemostasis. We report a new P-I class snake venom metalloproteinase (SVMP), barnettlysin-I (Bar-I), isolated from the venom of Bothrops barnetti and evaluated its fibrinolytic and antithrombotic potential. Bar-I was purified using a combination of molecular exclusion and cation-exchange chromatographies. We describe some biochemical features of Bar-I associated with its effects on hemostasis and platelet function. Bar-I is a 23.386 kDa single-chain polypeptide with pI of 6.7. Its sequence (202 residues) shows high homology to other members of the SVMPs. The enzymatic activity on dimethylcasein (DMC) is inhibited by metalloproteinase inhibitors e.g. EDTA, and by α2-macroglobulin. Bar-I degrades fibrin and fibrinogen dose- and time-dependently by cleaving their α-chains. Furthermore, it hydrolyses plasma fibronectin but not laminin nor collagen type I. In vitro Bar-I dissolves fibrin clots made either from purified fibrinogen or from whole blood. In contrast to many other P-I SVMPs, Bar-I is devoid of hemorrhagic activity. Also, Bar-I dose- and time-dependently inhibits aggregation of washed human platelets induced by vWF plus ristocetin and collagen (IC50=1.3 and 3.2 μM, respectively), presumably Bar-I cleaves both vWF and GPIb. Thus, it effectively inhibits vWF-induced platelet aggregation. Moreover, this proteinase cleaves the collagen-binding α2-A domain (160 kDa) of α2β1-integrin. This explains why it additionally inhibits collagen-induced platelet activation. A non-hemorrhagic but fibrinolytic metalloproteinase dissolves fibrin clots in vitro and impairs platelet function. This study provides new opportunities for drug development of a fibrinolytic agent with antithrombotic effect. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Normal postural responses preceding shoulder flexion: co-activation or asymmetric activation of transverse abdominis?

    Science.gov (United States)

    Davarian, Sanaz; Maroufi, Nader; Ebrahimi, Esmaeil; Parnianpour, Mohammad; Farahmand, Farzam

    2014-01-01

    It is suggested that activation of the transverse abdominis muscle has a stabilizing effect on the lumbar spine by raising intra-abdominal pressure without added disc compression. However, its feedforward activity has remained a controversial issue. In addition, research regarding bilateral activation of trunk muscles during a unilateral arm movement is limited. The aim of this study was to evaluate bilateral anticipatory activity of trunk muscles during unilateral arm flexion. Eighteen healthy subjects (aged 25 ± 3.96 years) participated in this study and performed 10 trials of rapid arm flexion in response to a visual stimulus. The electromyographic activity of the right anterior deltoid (AD) and bilateral trunk muscles including the transverse abdominis/internal oblique (TA/IO), superficial lumbar multifidus (SLM) and lumbar erector spine (LES) was recorded. The onset latency and anticipatory activity of the recorded trunk muscles were calculated. The first muscle activated in anticipation of the right arm flexion was the left TA/IO. The right TA/IO activated significantly later than all other trunk muscles (P 0.05). Healthy subjects showed no bilateral anticipatory co-activation of TA/IO in unilateral arm elevation. Further investigations are required to delineate normal muscle activation pattern in healthy subjects prior to prescribing bilateral activation training of transverse abdominis for subjects with chronic low back pain.

  11. Activity of pyrimidine degradation enzymes in normal tissues

    NARCIS (Netherlands)

    van Kuilenburg, A. B. P.; van Lenthe, H.; van Gennip, A. H.

    2006-01-01

    In this study, we measured the activity of dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase (DHP) and beta-ureidopropionase (beta-UP), using radiolabeled substrates, in 16 different tissues obtained at autopsy from a single patient. The activity of DPD could be detected in all tissues

  12. Door-to-needle time for administration of fibrinolytics in acute ...

    African Journals Online (AJOL)

    Objectives. To determine the current door-to-needle time for the administration of fibrinolytics for acute myocardial infarction (AMI) in emergency centres (ECs) at three hospitals in Cape Town, and to compare it with the American Heart Association/American College of Cardiology (AHA/ACC) recommendation of 30 minutes ...

  13. Fibrinolytic protease production by new Streptomyces sp. DPUA 1576 from Amazon lichens

    Directory of Open Access Journals (Sweden)

    Germana M.M. Silva

    2015-01-01

    Conclusions: These results show that the optimization of the culture medium can enhance protease production, thus becoming a good process for further research. In addition, Streptomyces sp. DPUA 1576, isolated from Amazon lichens, might be a potential strain for fibrinolytic protease production.

  14. Impact of fibrinolytics on the outcome of empyema in South African ...

    African Journals Online (AJOL)

    Results. One hundred and forty-two children with empyema, median age 17 months (interquartile range 8 - 43), were admitted during the study period. Excluding children who did not have a chest tube inserted and those in whom fibrinolysis was contraindicated, there were 99 patients, 52 of whom received fibrinolytics.

  15. Effect of urokinase thrombolysis on the cardiac function, coagulation, and fibrinolytic system in patients with AMI

    Directory of Open Access Journals (Sweden)

    Zhi-Bin Kuang

    2017-06-01

    Full Text Available Objective: To observe the effect of urokinase thrombolysis on the cardiac function, coagulation, and fibrinolytic system in patients with acute myocardial infarction (AMI. Methods: A total of 39 patients with AMI who were admitted in our hospital from March, 2016 to November, 2016 were included in the study and served as the observation group. The peripheral venous blood before and after thrombolysis was collected. The plasma NTproBNP level, related coagulation factors, and fibrinolysis indicators were detected. The cardiac function before treatment was evaluated. A total of 30 healthy individuals who came for physical examinations were served as the control group for contrastive analysis. Results: The plasma NT-proBNP, Fg, and D-D levels before thrombolysis in the observation group were significantly higher than those in the control group, while PT, APTT, and TT in the observation group were significantly shortened. The plasma NT-proBNP and D-D levels 2-48 h after thrombolysis in the observation group were significantly elevated first and reduced later and reached the peak 4 h after treatment, while PT, APTT, and TT were significantly extended first and shortened later. The plasma Fg level was significantly reduced first and elevated later and reached the minimum 4 h after treatment. During the treatment process, in the observation group, 2 had mucocutaneous hemorrhage, 3 had nasal hemorrhage, and 1 had gingival bleeding, but no gastrointestinal bleeding or cerebral hemorrhage occurred. Conclusions: The thrombolytic therapy can effectively reduce the coagulation activity in patients with AMI, strengthen the fibrinolysis activity, and improve the cardiac function.

  16. Mechanism of suppression of normal hemopoietic activity by lymphokine-activated killer cells and their products

    International Nuclear Information System (INIS)

    Gibson, F.M.; Malkovska, V.; Myint, A.A.; Meager, A.; Gordon-Smith, E.C.

    1991-01-01

    Interleukin 2 (IL-2)-activated lymphocytes (lymphokine-activated killer [LAK] cells) have been shown to inhibit the formation of autologous human granulocyte-macrophage hemopoietic progenitors (granulocyte-macrophage colony-forming units, CFU-GM) in vitro. Effects of LAK cells on these progenitors may include a number of different mechanisms. LAK cells are potent cytotoxic lymphocytes capable of lysing certain normal autologous cells. They also produce cytokines known to inhibit hemopoiesis (interferon gamma [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]) or enhance it (granulocyte-macrophage colony-stimulating factor, GM-CSF). In the authors' current study they analyzed the mechanism of suppression of autologous CFU-GM by LAK cells. Their results suggest that LAK cells are not directly cytotoxic to normal CFU-GM. They show that it is possible to abolish the hemopoiesis-inhibiting activity of LAK cells without abrogating their cytotoxicity against tumor cell lines using inhibitors of DNA synthesis, namely hydroxyurea or irradiation

  17. Constraining slip rates and spacings for active normal faults

    Science.gov (United States)

    Cowie, Patience A.; Roberts, Gerald P.

    2001-12-01

    Numerous observations of extensional provinces indicate that neighbouring faults commonly slip at different rates and, moreover, may be active over different time intervals. These published observations include variations in slip rate measured along-strike of a fault array or fault zone, as well as significant across-strike differences in the timing and rates of movement on faults that have a similar orientation with respect to the regional stress field. Here we review published examples from the western USA, the North Sea, and central Greece, and present new data from the Italian Apennines that support the idea that such variations are systematic and thus to some extent predictable. The basis for the prediction is that: (1) the way in which a fault grows is fundamentally controlled by the ratio of maximum displacement to length, and (2) the regional strain rate must remain approximately constant through time. We show how data on fault lengths and displacements can be used to model the observed patterns of long-term slip rate where measured values are sparse. Specifically, we estimate the magnitude of spatial variation in slip rate along-strike and relate it to the across-strike spacing between active faults.

  18. Physical activity patterns in morbidly obese and normal-weight women.

    Science.gov (United States)

    Kwon, Soyang; Mohammad, Jamal; Samuel, Isaac

    2011-01-01

    To compare physical activity patterns between morbidly obese and normal-weight women. Daily physical activity of 18 morbidly obese and 7 normal-weight women aged 30-58 years was measured for 2 days using the Intelligent Device for Energy Expenditure and Activity (IDEEA) device. The obese group spent about 2 hr/day less standing and 30 min/day less walking than did the normal-weight group. Time spent standing (standing time) was positively associated with time spent walking (walking time). Age- and walking time-adjusted standing time did not differ according to weight status. Promoting standing may be a strategy to increase walking.

  19. Risk for COPD with Obstruction of Active Smokers with Normal Spirometry and Reduced Diffusion Capacity

    Science.gov (United States)

    Kaner, Robert J.; Sanders, Abraham; Vincent, Thomas L.; Mezey, Jason G.; Crystal, Ronald G.

    2016-01-01

    Background Smokers are assessed for COPD using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusion capacity (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these “normal spirometry/low DLCO” smokers is unknown. Methods From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, CBC, urinalysis, HIV status, α1-antitrypsin level, chest X-ray, FEV1, FVC, FEV1/FVC ratio and total lung capacity (TLC). Throughout the study, all continued to be active smokers. Findings In the normal spirometry/normal DLCO group assessed over 45 ± 20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41 ± 31 months, 22% developed GOLD-defined COPD. Interpretation Despite appearing “normal” by GOLD, smokers with normal spirometry but low DLCO are at significant risk for developing COPD with obstruction to airflow. PMID:26541521

  20. Cardiorespiratory performance and physical activity in normal weight and overweight Finnish adolescents from 2003 to 2010.

    Science.gov (United States)

    Palomäki, Sanna; Heikinaro-Johansson, Pilvikki; Huotari, Pertti

    2015-01-01

    We investigated changes in cardiorespiratory performance, BMI and leisure-time physical activity among Finnish adolescents from 2003 to 2010. In addition, we compared cardiorespiratory performance levels between normal weight and overweight adolescents, grouped according to their physical activity. Participants were a national representative samples of 15-16-year-old adolescents in their final (ninth) year of comprehensive school in 2003 (n = 2258) and in 2010 (n = 1301). They performed an endurance shuttle run test and reported their height and weight and leisure time physical activity on a questionnaire. Results showed no significant secular changes in cardiorespiratory performance from 2003 to 2010. The mean BMI increased in boys. Leisure-time physical activity increased among normal weight girls. Adolescents of normal weight had better cardiorespiratory performance than those classified as overweight at both assessment points. BMI-adjusted physical activity was a significant determinant for cardiorespiratory performance among overweight adolescents, and very active overweight adolescents had similar cardiorespiratory performance levels as moderately active adolescents of normal weight. The results of the present study support the idea that the physical activity has the great importance for the cardiorespiratory performance in adolescents. Overweight adolescents, in particular, benefit from higher levels of physical activity.

  1. Risk of COPD with obstruction in active smokers with normal spirometry and reduced diffusion capacity.

    Science.gov (United States)

    Harvey, Ben-Gary; Strulovici-Barel, Yael; Kaner, Robert J; Sanders, Abraham; Vincent, Thomas L; Mezey, Jason G; Crystal, Ronald G

    2015-12-01

    Smokers are assessed for chronic obstructive pulmonary disease (COPD) using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation that is not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusing capacity of the lung for carbon monoxide (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these "normal spirometry/low DLCO" smokers is unknown.From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, complete blood count, urinalysis, HIV status, α1-antitrypsin level, chest radiography, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and total lung capacity. Throughout the study, all continued to be active smokers.In the normal spirometry/normal DLCO group assessed over 45±20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41±31 months, 22% developed GOLD-defined COPD.Despite appearing "normal" according to GOLD, smokers with normal spirometry but low DLCO are at significant risk of developing COPD with obstruction to airflow. Copyright ©ERS 2015.

  2. Physical activity patterns and estimated daily energy expenditures in normal and overweight tunisian schoolchildren.

    Science.gov (United States)

    Zarrouk, Fayçal; Bouhlel, Ezdine; Feki, Youssef; Amri, Mohamed; Shephard, Roy J

    2009-01-01

    Our aim was to test the normality of physical activity patterns and energy expenditures in normal weight and overweight primary school students. Heart rate estimates of total daily energy expenditure (TEE), active energy expenditure (AEE), and activity patterns were made over 3 consecutive school days in healthy middle-class Tunisian children (46 boys, 44 girls, median age (25(th)-75(th)) percentile, 9.2 (8.8-9.9) years. Our cross-section included 52 students with a normal body mass index (BMI) and 38 who exceeded age-specific BMI limits. TEE, AEE and overall physical activity level (PAL) were not different between overweight children and those with a normal BMI [median values (25(th)-75(th)) 9.20 (8.20-9.84) vs. 8.88 (7.42-9.76) MJ/d; 3.56 (2.59-4.22) vs. 3.85 (2.77-4.78) MJ/d and 1.74 (1.54-2.04) vs. 1.89 (1.66-2.15) respectively]. Physical activity intensities (PAI) were expressed as percentages of the individual's heart rate reserve (%HRR). The median PAI for the entire day (PAI24) and for the waking part of day (PAIw) were lower in overweight than in normal weight individuals [16.3 (14.2-18.9) vs. 20.6 (17.9-22.3) %HRR, p spend more time in moderate activity and less time in sedentary pursuits than overweight children.

  3. Physical activity levels of normal-weight and overweight girls and boys during primary school recess.

    Science.gov (United States)

    Stratton, Gareth; Ridgers, Nicola D; Fairclough, Stuart J; Richardson, David J

    2007-06-01

    This study aimed to compare moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) in normal-weight and overweight boys and girls during school recess. Four hundred twenty children, age 6 to 10 years, were randomly selected from 25 schools in England. Three hundred seventy-seven children completed the study. BMI was calculated from height and weight measurements, and heart rate reserve thresholds of 50% and 75% reflected children's engagement in MVPA and VPA, respectively. There was a significant main effect for sex and a significant interaction between BMI category and sex for the percent of recess time spent in MVPA and VPA. Normal-weight girls were the least active group, compared with overweight boys and girls who were equally active. Fifty-one boys and 24 girls of normal weight achieved the 40% threshold; of these, 30 boys and 10 girls exceeded 50% of recess time in MVPA. Eighteen overweight boys and 22 overweight girls exceeded the 40% threshold, whereas 8 boys and 8 girls exceeded the 50% threshold. Overweight boys were significantly less active than their normal-weight male counterparts; this difference did not hold true for girls. Even though nearly double the number of normal-weight children achieved the 40% of MVPA during recess compared with overweight children, physical activity promotion in school playgrounds needs to be targeted not only at overweight but at other health parameters, as 40 overweight children met the 40% MVPA target proposed for recess.

  4. Peer Popularity and Peer Communication Patterns: Hyperactive versus Active but Normal Boys.

    Science.gov (United States)

    King, Cheryl A.; Young, Richard David

    1981-01-01

    Classroom peer perceptions of 18 teacher-nominated hyperactive and 18 teacher-nominated active but normal elementary school-age boys were compared. Results indicated that hyperactives were significantly different from actives on all sociometric measures in that they were perceived more negatively. (Author/SB)

  5. Physical activity during pregnancy in normal-weight and obese women

    DEFF Research Database (Denmark)

    Renault, K; Nørgaard, K; Secher, N J

    2012-01-01

    The objectives of this prospective study were to compare physical activity in 70 normal-weight women with a body mass index (BMI) 20-25 kg/m(2), and 70 obese with a BMI ≥ 30 kg/m(2), before and during pregnancy, and to compare compliance using the pedometer. Physical activity before pregnancy was...

  6. Physical activity during pregnancy in obese and normal-weight women as assessed by pedometer

    DEFF Research Database (Denmark)

    Renault, Kristina; Nørgaard, Kirsten; Andreasen, Kirsten Riis

    2010-01-01

    OBJECTIVE: To compare physical activity as assessed by a pedometer in obese and normal-weight pregnant women at different gestational ages. To evaluate the use of a pedometer in pregnancy. DESIGN: Cross-sectional study. SETTING: Department of obstetrics and gynecology in a university hospital...... in Copenhagen. POPULATION: 338 pregnant women, 175 normal-weight women with body mass index (BMI) 20-25 kg/m(2) and 163 obese women with BMI > or = 30 kg/m(2). METHODS: Physical activity was assessed by a pedometer (Yamax Digiwalker SW-700/701) on seven consecutive days in six different groups: normal......-weight or obese at gestational ages 11-13, 18-22, and 36-38, and expressed as median number of daily steps during a whole week, working days, and weekends. MAIN OUTCOME MEASURES: Relation between BMI and physical activity during pregnancy and compliance with wearing the pedometer. RESULTS: Noncompliance was more...

  7. Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S. [Korea Atomic Emergy Research Institute, Seoul (Korea, Republic of)

    1973-03-15

    The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

  8. Effect of Diuresis on Plasma Renin Activity and Aldosterone Concentration in Normal and Toxemic Pregnancy

    International Nuclear Information System (INIS)

    Sung, H. K.; Lee, H. S.; Cho, S. S.; Koh, J. H.; Lee, J. K.; Kim, H. S.

    1973-01-01

    The changes of plasma renin activity, aldosterone concentration, serum sodium, and potassium levels were studied before and after the water loading followed by diuretics injection. The materials were: 13 non-, 11 normal-, and 11 toxemic pregnancy cases. The plasma renin activity and aldosterone concentration of the cord and postpartum blood were also measured. Following were the results: 1. The plasma renin activity was elevated significantly in normal pregnancy, and slightly in toxemic pregnancy. The serum sodium levels were decreased in pregnancy. 2. The plasma aldosterone concentration was slightly decreased in normal pregnancy, and slightly increased in toxemic pregnancy, however, statistically insignificant. 3. The plasma renin activity of the cord and postpartum blood were lower than those of pregnancy cases. 4. The changes of plasma renin activity after the diuretic administration showed an initial increase, which recovered within 2 hours. These changes were the least in normal pregnancy, and the most in toxemic pregnancy. 5. The changes of plasma aldosterone concentration after the diuretic administration were similar to those of plasma renin activity, although the variations were not so wide.

  9. Production of fibrinolytic protease from Streptomyces lusitanus isolated from marine sediments

    Science.gov (United States)

    SudeshWarma, S.; Merlyn keziah, S.; Subathra Devi, C.

    2017-11-01

    This study aim was to isolate, screen, characterize and optimize marine Streptomyces for fibrinolytic enzyme production. The potent actinomycete isolate was subjected to optimization. The parameters for optimization included pH, temperature, carbon, nitrogen sources. The crude supernatant produced was purified using size exclusion gel filtration chromatography. The optimized parameters for maximum productivity were found to be pH 7, 37°C, maltose and peptone respectively. The molecular weight of the purified enzyme was found to be 21kDa.

  10. Medium Optimization for the Production of Fibrinolytic Enzyme by Paenibacillus sp. IND8 Using Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Ponnuswamy Vijayaraghavan

    2014-01-01

    Full Text Available Production of fibrinolytic enzyme by a newly isolated Paenibacillus sp. IND8 was optimized using wheat bran in solid state fermentation. A 25 full factorial design (first-order model was applied to elucidate the key factors as moisture, pH, sucrose, yeast extract, and sodium dihydrogen phosphate. Statistical analysis of the results has shown that moisture, sucrose, and sodium dihydrogen phosphate have the most significant effects on fibrinolytic enzymes production (P<0.05. Central composite design (CCD was used to determine the optimal concentrations of these three components and the experimental results were fitted with a second-order polynomial model at 95% level (P<0.05. Overall, 4.5-fold increase in fibrinolytic enzyme production was achieved in the optimized medium as compared with the unoptimized medium.

  11. Normalization of voltage-sensitive dye signal with functional activity measures.

    Directory of Open Access Journals (Sweden)

    Kentaroh Takagaki

    Full Text Available In general, signal amplitude in optical imaging is normalized using the well-established DeltaF/F method, where functional activity is divided by the total fluorescent light flux. This measure is used both directly, as a measure of population activity, and indirectly, to quantify spatial and spatiotemporal activity patterns. Despite its ubiquitous use, the stability and accuracy of this measure has not been validated for voltage-sensitive dye imaging of mammalian neocortex in vivo. In this report, we find that this normalization can introduce dynamic biases. In particular, the DeltaF/F is influenced by dye staining quality, and the ratio is also unstable over the course of experiments. As methods to record and analyze optical imaging signals become more precise, such biases can have an increasingly pernicious impact on the accuracy of findings, especially in the comparison of cytoarchitechtonic areas, in area-of-activation measurements, and in plasticity or developmental experiments. These dynamic biases of the DeltaF/F method may, to an extent, be mitigated by a novel method of normalization, DeltaF/DeltaF(epileptiform. This normalization uses as a reference the measured activity of epileptiform spikes elicited by global disinhibition with bicuculline methiodide. Since this normalization is based on a functional measure, i.e. the signal amplitude of "hypersynchronized" bursts of activity in the cortical network, it is less influenced by staining of non-functional elements. We demonstrate that such a functional measure can better represent the amplitude of population mass action, and discuss alternative functional normalizations based on the amplitude of synchronized spontaneous sleep-like activity. These findings demonstrate that the traditional DeltaF/F normalization of voltage-sensitive dye signals can introduce pernicious inaccuracies in the quantification of neural population activity. They further suggest that normalization

  12. Analysis of EMG Signals in Aggressive and Normal Activities by Using Higher-Order Spectra

    Directory of Open Access Journals (Sweden)

    Necmettin Sezgin

    2012-01-01

    Full Text Available The analysis and classification of electromyography (EMG signals are very important in order to detect some symptoms of diseases, prosthetic arm/leg control, and so on. In this study, an EMG signal was analyzed using bispectrum, which belongs to a family of higher-order spectra. An EMG signal is the electrical potential difference of muscle cells. The EMG signals used in the present study are aggressive or normal actions. The EMG dataset was obtained from the machine learning repository. First, the aggressive and normal EMG activities were analyzed using bispectrum and the quadratic phase coupling of each EMG episode was determined. Next, the features of the analyzed EMG signals were fed into learning machines to separate the aggressive and normal actions. The best classification result was 99.75%, which is sufficient to significantly classify the aggressive and normal actions.

  13. Analysis of EMG Signals in Aggressive and Normal Activities by Using Higher-Order Spectra

    Science.gov (United States)

    Sezgin, Necmettin

    2012-01-01

    The analysis and classification of electromyography (EMG) signals are very important in order to detect some symptoms of diseases, prosthetic arm/leg control, and so on. In this study, an EMG signal was analyzed using bispectrum, which belongs to a family of higher-order spectra. An EMG signal is the electrical potential difference of muscle cells. The EMG signals used in the present study are aggressive or normal actions. The EMG dataset was obtained from the machine learning repository. First, the aggressive and normal EMG activities were analyzed using bispectrum and the quadratic phase coupling of each EMG episode was determined. Next, the features of the analyzed EMG signals were fed into learning machines to separate the aggressive and normal actions. The best classification result was 99.75%, which is sufficient to significantly classify the aggressive and normal actions. PMID:23193379

  14. [Cell-derived microparticles unveil their fibrinolytic and proteolytic function].

    Science.gov (United States)

    Doeuvre, Loïc; Angles-Cano, Eduardo

    2009-01-01

    Cell-derived microparticles (MP) are membrane microvesicles, 0.1-1 microm in size, shed by cells following activation or during apoptosis in a variety of pathological conditions. MPs released by blood cells or by vascular endothelial cells display molecular signatures that allow their identification and functional characterization. In addition, they provide tissue factor (TF) and a procoagulant phospholipid surface. Therefore, at present, the most strongly established applied research on MPs is their procoagulant activity as a determinant of thrombotic risk in various clinical conditions. Previous studies have indicated that MPs derived from malignant cells express matrix metalloproteinases, urokinase and its receptor (uPA/uPAR) that, in the presence of plasminogen, may act in concert to degrade extracellular matrix proteins. Recently, it was shown that MPs from TNFa-stimulated endothelial cells served as a surface for interaction with plasminogen and its conversion into plasmin by the uPA/uPAR system expressed at their surface. This capacity of MPs to promote plasmin generation confers them a new profibrinolytic and proteolytic function that may be of relevance in fibrinolysis, cell migration, angiogenesis, dissemination of malignant cells, cell detachment and apoptosis.

  15. Impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women.

    Science.gov (United States)

    Surekha, T; Himabindu, Y; Sriharibabu, M; Pandey, Anil Kumar

    2014-01-01

    Physical inactivity is a leading risk factor for overweight and obesity in the society. Prevalence of overweight and obesity in the reproductive age group women not only affects maternal health but also the health of the off spring. Infertility is a common problem in India affecting 13-19 million people at any given time. Even though it is not life threatening, infertility causes intense mental agony and trauma that can only be best described by infertile couples themselves. Infertility is more common in overweight and obese individuals compared to normal weight individuals. Decreasing ovarian reserve is an important factor for infertility in women. This study examined the impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women. The observations made in this study reveal that physical activity improves ovarian reserve markers in all reproductive age women but this improvement is more distinct and statistically significant in overweight and obese women compared to normal weight women.

  16. Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

    International Nuclear Information System (INIS)

    Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

    1984-01-01

    Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient

  17. Physical Activity Patterns in Normal-Weight and Overweight/Obese Pregnant Women.

    Directory of Open Access Journals (Sweden)

    Elisabetta Bacchi

    Full Text Available The aims of the present study were to assess the volume of physical activity (PA throughout pregnancy in normal-weight vs overweight/obese women, and to investigate which factors may predict compliance to PA recommendations in these women throughout gestation. In 236 pregnant women, 177 normal-weight and 59 overweight/obese (median[IQR] BMI 21.2[19.9-22.8] vs 26.5[25.5-29.0] kg/m2, respectively, medical history, anthropometry and clinical data, including glucose tolerance, were recorded. In addition, pre-pregnancy PA was estimated by the Kaiser questionnaire, while total, walking and fitness/sport PA during pregnancy were assessed by the Physical Activity Scale for the Elderly (PASE modified questionnaire, at 14-16, 24-28 and 30-32 weeks of gestation. PA volume was very low in the first trimester of pregnancy in both groups of women. However, it increased in the second and third trimester in normal-weight, but not in overweight/obese subjects. Higher pre-pregnancy PA was a statistically significant predictor of being physically active (>150 minutes of PA per week during all trimesters of gestation. In conclusion, physical activity volume is low in pregnant women, especially in overweight/obese subjects. PA volume increases during pregnancy only in normal-weight women. Pre-pregnancy PA is an independent predictor of achieving a PA volume of at least 150 min per week during pregnancy.

  18. Physical activity during pregnancy in obese and normal-weight women as assessed by pedometer

    DEFF Research Database (Denmark)

    Renault, Kristina; Nørgaard, Kirsten; Andreasen, Kirsten Riis

    2010-01-01

    OBJECTIVE: To compare physical activity as assessed by a pedometer in obese and normal-weight pregnant women at different gestational ages. To evaluate the use of a pedometer in pregnancy. DESIGN: Cross-sectional study. SETTING: Department of obstetrics and gynecology in a university hospital in ...

  19. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz

    2016-01-01

    in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

  20. Attitude toward physical activity in normal-weight, overweight and obese adolescents.

    Science.gov (United States)

    Deforche, Benedicte I; De Bourdeaudhuij, Ilse M; Tanghe, Ann P

    2006-05-01

    To investigate differences in physical activity and attitude toward physical activity in adolescents with different degrees of overweight and explore whether the prediction of physical activity by attitude is moderated by level of overweight. Subjects were divided into a normal-weight group (n = 37, 18.8 +/- 1.2 kg/m2), an overweight group (n = 28, 25.9 +/- 1.3 kg/m2), and an obese group (n = 24, 33.7 +/- 4.1 kg/m2). Mean age was 14.6 +/- 1.2 years, with 72% girls. Physical activity was estimated using the Baecke Questionnaire. Attitude was measured by assessing perceived benefits and barriers. Participation in sports was higher in normal-weight compared with overweight (p attitude compared with their normal-weight (p attitude was not moderated by level of overweight. This study demonstrates that overweight and obese adolescents show lower sport participation and have a less positive attitude toward physical activity. Interventions in youngsters with weight problems should try to increase participation in sports by making activities more fun and attractive for these youngsters.

  1. Physical activity and self-efficacy in normal and over-fat children.

    Science.gov (United States)

    Suton, Darijan; Pfeiffer, Karin A; Feltz, Deborah L; Yee, Kimbo E; Eisenmann, Joey C; Carlson, Joseph J

    2013-09-01

    To examine the independent and combined association of self-efficacy and fatness with physical activity in 5(th) grade children. Participants were 281 students (10.4 ± 0.7 years). Physical activity was assessed using a self-report question. Self-efficacy to be physically active was assessed using a 5-point scale. Body fatness was assessed by bioelectrical impedance. Descriptive statistics, ANOVA, and t-tests were used. There were no differences in reported days of physical activity between boys and girls, and normal-fat and over-fat children. However, children with high self-efficacy participated in significantly more physical activity compared to their low self-efficacy counterparts (3.4 ± 2.0 days vs. 5.4 ± 1.8 days, respectively, p < .001). Only physical activity self-efficacy was related to physical activity, fatness was not.

  2. Study of chromium speciation in normal and diabetic rats by activable enriched stable isotope technique

    International Nuclear Information System (INIS)

    Feng, W.Y.; Qian, Q.F.; Ding, W.J.; Chai, Z.F.

    2000-01-01

    Chromium speciation was investigated in the liver cytosol, serum and urine of normal and diabetic rats after a single intravenous injection of enriched stable isotope 50 Cr tracer solution. Sephadex G-25 gel chromatography combined with instrumental neutron activation analysis was used to isolate and characterize protein-bound chromium in the above materials. The results indicate that Cr is mainly combined with a high-molecular-weight protein either in liver cytosol or serum. A low-molecular-weight, Cr-containing compound (LMWCr) was found in all the observed liver, serum and urine samples of both normal and diabetic rats. Chromium is excreted chiefly as LMWCr in urine. (author)

  3. Effects of low dose irradiation on NK activity of normal individuals and patients with cancer

    International Nuclear Information System (INIS)

    Tian Hailin; Su Liaoyuan

    1994-10-01

    Effects of low dose irradiation on NK activity of lymphocytes and on K 562 cells were studied. The NK activity was determined by means of 3 H-TdR release assay. While 3 H-TdR incorporation was used to reflect functional changes of K 562 cells after low dose irradiation. 21 patients with cancer and 10 normal individuals were detected. The results indicated that the NK activity of lymphocytes in normal individuals increased significantly after 10 and 50 cGy γ-ray irradiation, while in patients with cancer the NK activity of lymphocytes increased only at the dose of 50 cGy irradiation. The increase of NK activity in normal individuals was higher than that in patients with cancer after same doses of irradiation. When K 562 cells were irradiated by 10 cGy γ-rays, the 3 H-TdR incorporation value increased. After exposed to over 50 cGy the stimulating effect disappeared

  4. Purification and characterization of a fibrinolytic enzyme of Bacillus subtilis DC33, isolated from Chinese traditional Douchi

    NARCIS (Netherlands)

    Wang, C.T.; Ji, B.P.; Li, B.; Nout, M.J.R.; Li, P.L.; Ji, H.; Chen, L.F.

    2006-01-01

    Bacillus subtilis DC33 producing a novel fibrinolytic enzyme was isolated from Ba-bao Douchi, a traditional soybean-fermented food in China. The strong fibrin-specific enzyme subtilisin FS33 was purified to electrophoretic homogeneity using the combination of various chromatographic steps. The

  5. Protein C activation during the initial phase of experimental acute pancreatitis in the rabbit

    DEFF Research Database (Denmark)

    Ottesen, L H; Bladbjerg, E-M; Osman, M

    2000-01-01

    activity), anticoagulant proteins (protein C, antithrombin) and fibrinolytic factors (tissue plasminogen activator, plasminogen activator inhibitor-1) were performed for 5 h. RESULTS: ANP was confirmed by elevated serum amylase, development of ascites, and histological changes of the pancreas. A moderate...

  6. Evaluation of Postprandial Total Antioxidant Activity in Normal and Overweight Individuals

    Directory of Open Access Journals (Sweden)

    Fatma Arslan

    2016-09-01

    Full Text Available Aim: Postprandial changes acutely alter some mechanisms in body. There are many studies showing blood oxidative status changes after food intake, and supplementation. The aim of the present study was to evaluate the effects of a standardized meal on serum total antioxidant activity (TAA in normal weight and overweight individuals. Material and Method: Fourteen normal weight and twelve overweight individuals were given a standardized meal in the morning after an overnight fast. Serum TAA, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride concentrations were measured at baseline, 3rd hour, and 6th hour after the meal in both groups.Results: In both normal and overweight groups, the difference between baseline and 3rd hour was significant for TAA. The TAA of the overweight group was also significantly lower than the TAA of the normal weight group at 3rd hour. However, there was no significant correlation between lipid parameters and TAA levels. Discussion: The present study shows that postprandial oxidative damage occurs more prominently in overweight individuals than in normal weight individuals. Postprandial changes acutely induce oxidative stress and impair the natural antioxidant defense mechanism. It should be noted that consuming foods with antioxidants in order to avoid various diseases and complications is useful, particularly in obese subjects.

  7. Results of dose calculations for NET accidental and normal operation releases of tritium and activation products

    International Nuclear Information System (INIS)

    Raskob, W.; Hasemann, I.

    1992-08-01

    This report documents conditions, data and results of dose calculations for accidental and normal operation releases of tritium and activation products, performed within the NET subtask SEP2.2 ('NET-Benchmark') of the European Fusion Technology Programme. For accidental releases, the computer codes UFOTRI and COSYMA for assessing the radiological consequences, have been applied for both deterministic and probabilistic calculations. The influence on dose estimates of different release times (2 minutes / 1 hour), two release heights (10 m / 150 m), two chemical forms of tritium (HT/HTO), and two different model approaches for the deposition velocity of HTO on soil was investigated. The dose calculations for normal operation effluents were performed using the tritium model of the German regulatory guidelines, parts of the advanced dose assessment model NORMTRI still under development, and the statistical atmospheric dispersion model ISOLA. Accidental and normal operation source terms were defined as follows: 10g (3.7 10 15 Bq) for accidental tritium releases, 10 Ci/day (3.7 10 11 Bq/day) for tritium releases during normal operation and unit releases of 10 9 Bq for accidental releases of activation products and fission products. (orig./HP) [de

  8. Expression of Peroxisomes-Proliferate Activated Receptors-γ in Diabetics, Obese and Normal Subjects

    International Nuclear Information System (INIS)

    Afzal, N.

    2016-01-01

    Background: Current research in type 2 diabetes mellitus focuses on the role of Peroxisome-Proliferator Activated Receptors (PPARs) in the pathogenesis of the Insulin Resistance Syndrome (IRS), which are pre-diabetic lesion and the hallmark of fully developed type 2 diabetes mellitus. This study aims at identifying the abnormal status of the PPAR-g in adipose tissues of type 2 diabetes mellitus patients, when compared with matched normal controls. Methods: This cross-sectional study was conducted in Ayub Medical College, Abbottabad, from 2012 to 2014. Sample included three equal groups of patients. Group-1 with diagnosed type 2 diabetes mellitus, aged 40-65 years, acting as the test group, Group-2 included non-diabetic obese, and Group-3 with normal subjects. Transcription Factor Assay for Peroxisome Proliferator Activated Receptor Gamma (gamma PPAR) was done on ELISA Technique from Nuclear Extract procured from Adipose Tissue of the subjects. Results: Mean age of enrolled participants was 48.93 SD±6.52.years. Patients ranged between ages of 40 years to 67 years. The mean values of PPAR in normal, obese and diabetic group were 1.72 SD±0.28, 1.282 SE±0.18 and 1.283 SE±0.18 respectively. The difference in mean values of PPAR was significant ρ<0.05. Conclusion: The levels of PPAR-g in patients with type 2 Diabetes Mellitus and Obese cases are significantly lower than normal controls. (author)

  9. Insulin Signaling-independent Activation of DAF-16 Shapes the Transcriptome during Normal Aging

    OpenAIRE

    Zhang, Yan-Ping; Liang, Chung-Yi; Hsu, Ao-Lin; Li, Shang-Tong; Zhang, Pan; Dong, Meng-Qiu; Zhao, Han-Qing

    2018-01-01

    The roles and regulatory mechanisms of transriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age-associated down-regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF-16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF-16 translocates into the nucleus in aged wild-type worms and activates the exp...

  10. Elevated testosterone and hypergonadotropism in active adolescents of normal weight with oligomenorrhea.

    Science.gov (United States)

    Singer, K; Rosenthal, A; Kasa-Vubu, Josephine Z

    2009-10-01

    Oligomenorrhea in active adolescent females of normal weight is presumed to be related to hypoestrogenism secondary to physical activity and decreased fat mass. We hypothesized that active adolescents with oligomenorrhea would have lower estrogen levels than normal controls with similar levels of cardiovascular fitness. Twenty healthy participants between the ages of 16 and 20 years were recruited at least 2 years postmenarche. Adolescents reporting fewer than 9 cycles a year (n = 6) were compared to 14 controls with monthly menstrual cycles. Histories of eating disorder, hirsutism, severe acne, depression, or amenorrhea were cause for exclusion. Body composition and bone density were measured by total body dual x-ray absorpitometry. Cardiovascular fitness was evaluated by measuring oxygen consumption during exercise. Control subjects were matched by age, body mass index (BMI), and fitness level. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, progesterone, and estradiol were obtained. Statistical analysis was performed using SAS 9.1. Cardiovascular fitness in both groups was within normal limits for age. No significant differences in BMI, estradiol concentrations, or bone density were found, but trunk fat mass was lower in adolescents with oligomenorrhea who also reported more frequent exercise. Testosterone concentrations and LH/FSH ratios were significantly higher in participants with irregular menstrual cycles (P = 0.0018 and exercise-induced oligomenorrhea.

  11. Changes in auxin activity in tumourous and normal tobacco calluses treated with morphactin IT 3233

    Directory of Open Access Journals (Sweden)

    Z. Chirek

    2015-01-01

    Full Text Available The addition of morphactin IT 3233 in 1-40 mg/dm3 concentrations to the medium inhibited the growth in vitro of normal and tumourous tobacco calluses. The auxin activity (estimated by the Avena coleoptile straight growth test of the acid ether extracts from these tissues increased. The activity of zone I (Rf 0.2-0.4, 0.5, solvent system: butanol:water:ammonia 10:10:1 in normal tissues increased more intensively than that of zone II (Rf 0.6-0.8, 0.9. In tumourous tissues, however, these changes were smaller and they concerned merely zone I of auxin activity (Rf 0.0-0.5. It seems that the mechanism of morphactin activity in both kinds of tissue is different. It may be supposed that the excessive accumulation of auxins induces growth inhibition of tissues. A previously found increase in the activity of IAA-oxidase influenced by morphactin might be considered as an adaptation to a higher level of IAA.

  12. NaV1.6a is required for normal activation of motor circuits normally excited by tactile stimulation

    Science.gov (United States)

    Low, Sean E.; Zhou, Weibin; Choong, Xinling; Saint-Amant, Louis; Sprague, Shawn M.; Hirata, Hiromi; Cui, Wilson W.; Hume, Richard I.; Kuwada, John Y.

    2010-01-01

    A screen for zebrafish motor mutants identified two non-complementing alleles of a recessive mutation that were named non-active (navmi89 and navmi130). nav embryos displayed diminished spontaneous and touch-evoked escape behaviors during the first three days of development. Genetic mapping identified the gene encoding NaV1.6a (scn8aa) as a potential candidate for nav. Subsequent cloning of scn8aa from the two alleles of nav uncovered two missense mutations in NaV1.6a that eliminated channel activity when assayed heterologously. Furthermore the injection of RNA encoding wild type scn8aa rescued the nav mutant phenotype indicating that scn8aa was the causative gene of nav. In vivo electrophysiological analysis of the touch-evoked escape circuit indicated that voltage-dependent inward current was decreased in mechanosensory neurons in mutants, but they were able to fire action potentials. Furthermore tactile stimulation of mutants activated some neurons downstream of mechanosensory neurons but failed to activate the swim locomotor circuit in accord with the behavioral response of initial escape contractions but no swimming. Thus mutant mechanosensory neurons appeared to respond to tactile stimulation but failed to initiate swimming. Interestingly fictive swimming could be initiated pharmacologically suggesting that a swim circuit was present in mutants. These results suggested that NaV1.6a was required for touch-induced activation of the swim locomotor network. PMID:20225246

  13. Most Children With Epilepsy Experience Postictal Phenomena, Often Preventing a Return to Normal Activities of Childhood.

    Science.gov (United States)

    MacEachern, Sarah J; D'Alfonso, Sabrina; McDonald, Roman J; Thornton, Nancy; Forkert, Nils D; Buchhalter, Jeffrey R

    2017-07-01

    After a seizure, individuals with epilepsy have reported diverse symptoms in the postictal period, especially motor and cognitive dysfunction. However, these phenomena have not been well characterized in children, and their impact on patient well-being is not understood. We hypothesized that in a subset of epilepsy patients, postictal symptoms would affect their ability to return to normal childhood activities. To test our hypothesis, a survey-based approach was used to characterize the type, frequency, and duration, as well as the impact of these symptoms on the ability of these children to return to their normal activities. In this prospective study, data were analyzed from 208 patients seen in the pediatric neurology outpatient clinic at the Alberta Children's Hospital. We found that 86% (179 out of 208) of respondents reported postictal symptoms, with the most common symptom category being fatigue, sleepiness, and/or tiredness (90%; 161 of 179). The greatest impact resulted from weakness or being unable to move normally, which prevented 78% of those affected (71 of 91) from returning to normal activities after a seizure. Children who had focal seizures were more likely to experience postictal fatigue, sleepiness, or tiredness (P = 0.01; Bonferroni corrected), but no other postictal symptoms were significantly associated with a specific seizure type or epilepsy syndrome. The results of this study further our understanding of the frequency, type, and duration of symptoms experienced in the postictal period and how these symptoms impact children with epilepsy. It is clear that postictal phenomena often occur after epileptic seizures and have a significant impact on the lives of children with epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Cerebellar activation in verb generation. Activation study with positron emission tomography in normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Eriko [Inst. for Rehabilitation and Mental Health, Kyowa, Akita (Japan); Kanno, Iwao; Sadato, Norihiro; Senda, Michio; Fujita, Hideaki; Nagata, Ken

    1999-06-01

    To investigate the role of cerebellum in language function, we used the silent verb generation task in PET activation study. Subjects were 11 right-handed, healthy men with the mean age of 24.3. We used two experimental conditions, resting state and verb generation, and measured cerebral blood flow (CBF) alternately and repeatedly, three times for each condition. In the verb generation task, the subject was asked to silently think of as many verbs associated with auditorily given noun as he could. The subtraction image between verb generation and resting state showed activation foci at the left inferior to middle frontal lobe as well as temporal lobe in the supratentorium, consistent with previous studies. In the infratentorium, there were significant foci at bilateral cerebellar hemisphere and brain stem, which was predominantly seen over the right cerebellum. Activations were seen in the superior-lateral part of the right cerebellar hemisphere including the right dentate nucleus, and in the inferior-lateral part of the left cerebellar hemisphere. The amount of CBF increase by the task as compared with the resting condition in the upper cerebellum showed an increasing trend from the first to the third measurement. The present results suggest specific roles of the cerebellum in word retrieval as well as the practice-related changes during verbal learning. (author)

  15. Cerebellar activation in verb generation. Activation study with positron emission tomography in normal subjects

    International Nuclear Information System (INIS)

    Yokoyama, Eriko; Kanno, Iwao; Sadato, Norihiro; Senda, Michio; Fujita, Hideaki; Nagata, Ken

    1999-01-01

    To investigate the role of cerebellum in language function, we used the silent verb generation task in PET activation study. Subjects were 11 right-handed, healthy men with the mean age of 24.3. We used two experimental conditions, resting state and verb generation, and measured cerebral blood flow (CBF) alternately and repeatedly, three times for each condition. In the verb generation task, the subject was asked to silently think of as many verbs associated with auditorily given noun as he could. The subtraction image between verb generation and resting state showed activation foci at the left inferior to middle frontal lobe as well as temporal lobe in the supratentorium, consistent with previous studies. In the infratentorium, there were significant foci at bilateral cerebellar hemisphere and brain stem, which was predominantly seen over the right cerebellum. Activations were seen in the superior-lateral part of the right cerebellar hemisphere including the right dentate nucleus, and in the inferior-lateral part of the left cerebellar hemisphere. The amount of CBF increase by the task as compared with the resting condition in the upper cerebellum showed an increasing trend from the first to the third measurement. The present results suggest specific roles of the cerebellum in word retrieval as well as the practice-related changes during verbal learning. (author)

  16. In-vitro activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota.

    Science.gov (United States)

    Weintraub, Andrej; Rashid, Mamun-Ur; Nord, Carl Erik

    2016-12-01

    Solithromycin is a novel fluoroketolide with high activity against bacteria associated with community-acquired respiratory tract infections as well as gonorrhea. However, data on the activity of solithromycin against anaerobic bacteria from the normal intestinal microbiota are scarce. In this study, 1024 Gram-positive and Gram-negative anaerobic isolates from the normal intestinal microbiota were analyzed for in-vitro susceptibility against solithromycin and compared to azithromycin, amoxicillin/clavulanic acid, ceftriaxone, metronidazole and levofloxacin by determining the minimum inhibitory concentration (MIC). Solithromycin was active against Bifidobacteria (MIC 50 , 0.008 mg/L) and Lactobacilli (MIC 50 , 0.008 mg/L). The MIC 50 for Clostridia, Bacteroides, Prevotella and Veillonella were 0.5, 0.5, 0.125 and 0.016 mg/L, respectively. Gram-positive anaerobes were more susceptible to solithromycin as compared to the other antimicrobials tested. The activity of solithromycin against Gram-negative anaerobes was equal or higher as compared to other tested agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Normal levels of total body sodium and chlorine by neutron activation analysis

    International Nuclear Information System (INIS)

    Kennedy, N.S.J.; Eastell, R.; Smith, M.A.; Tothill, P.

    1983-01-01

    In vivo neutron activation analysis was used to measure total body sodium and chlorine in 18 male and 18 female normal adults. Corrections for body size were developed. Normalisation factors were derived which enable the prediction of the normal levels of sodium and chlorine in a subject. The coefficient of variation of normalised sodium was 5.9% in men and 6.9% in women, and of normalised chlorine 9.3% in men and 5.5% in women. In the range examined (40-70 years) no significant age dependence was observed for either element. Total body sodium was correlated with total body chlorine and total body calcium. Sodium excess, defined as the amount of body sodium in excess of that associated with chlorine, also correlated well with total body calcium. In females there was a mean annual loss of sodium excess of 1.2% after the menopause, similar to the loss of calcium. (author)

  18. Patterns of brain activity in normals and schizophrenics with positron emission tomography

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wolf, A.P.; Gomez-Mont, F.; Brodie, J.D.; Canero, R.; Van Gelder, P.; Russell, J.A.G.

    1985-01-01

    The authors investigated the functional interaction among brain areas under baseline and upon activation by a visual task to compare the response of normal subjects from the ones of chronic schizophrenics. Cerebral metabolic images were obtained on twelve healthy volunteers an eighteen schizophrenics with positron emission tomography and 11-C-Deoxyglucose. Correlation coefficients among the relative metabolic values (region of interest divided by the average of whole brain gray matter) of 11 brain regions; frontal, parietal, temporal and occipital left and right lobes, left and right basal ganglia and thalamus were computed for the baseline and for the task. Under baseline, normals showed more functional correlations than schizophrenics. Both groups showed a thalamo-occipital (positive) and thalamo-frontal (negative) interaction. The highest correlations among homologous brain areas were the frontal, occipital and basal ganglia

  19. Sleep habits, food intake, and physical activity levels in normal and overweight and obese Malaysian children.

    Science.gov (United States)

    Firouzi, Somayyeh; Poh, Bee Koon; Ismail, Mohd Noor; Sadeghilar, Aidin

    2014-01-01

    This study aimed to determine the association between sleep habits (including bedtime, wake up time, sleep duration, and sleep disorder score) and physical characteristics, physical activity level, and food pattern in overweight and obese versus normal weight children. Case control study. 164 Malaysian boys and girls aged 6-€“12 years. Anthropometric measurements included weight, height, waist circumference, and body fat percentage. Subjects divided into normal weight (n = 82) and overweight/obese (n = 82) group based on World Health Organization 2007 BMI-for-age criteria and were matched one by one based on ethnicity, gender, and age plus minus one year. Questionnaires related to sleep habits, physical activity, and food frequency were proxy-reported by parents. Sleep disorder score was measured by Children Sleep Habit Questionnaire. Sleep disorder score and carbohydrate intake (%) to total energy intake were significantly higher in overweight/obese group (p < 0.01 and p < 0.05, respectively). After adjusting for age and gender, sleep disorder score was correlated with BMI (r = 0.275, p < 0.001), weight (r = 0.253, p < 0.001), and WC (r = 0.293, p < 0.001). Based on adjusted odd ratio, children with shortest sleep duration were found to have 4.5 times higher odds of being overweight/obese (odd ratio: 4.536, 95% CI: 1.912-€“8.898) compared to children with normal sleep duration. The odds of being overweight/obese in children with sleep disorder score higher than 48 were 2.17 times more than children with sleep disorder score less than 48. Children who sleep lees than normal amount, had poor sleep quality, and consumed more carbohydrates were at higher risk of overweight/obesity. © 2014 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

  20. Normally occurring environmental and behavioral influences on gene activity: from central dogma to probabilistic epigenesis.

    Science.gov (United States)

    Gottlieb, G

    1998-10-01

    The central dogma of molecular biology holds that "information" flows from the genes to the structure of the proteins that the genes bring about through the formula DNA-->RNA-->Protein. In this view, a set of master genes activates the DNA necessary to produce the appropriate proteins that the organism needs during development. In contrast to this view, probabilistic epigenesis holds that necessarily there are signals from the internal and external environment that activate DNA to produce the appropriate proteins. To support this view, a substantial body of evidence is reviewed showing that external environmental influences on gene activation are normally occurring events in a large variety of organisms, including humans. This demonstrates how genes and environments work together to produce functional organisms, thus extending the author's model of probabilistic epigenesis.

  1. Insulin secretion enhancing activity of roselle calyx extract in normal and streptozotocin-induced diabetic rats

    Science.gov (United States)

    Wisetmuen, Eamruthai; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Yutanawiboonchai, Wiboonchai; Itharat, Arunporn

    2013-01-01

    Background and Objective: Our recent study revealed the antihyperglycemic activity of an ethanolic extract of roselle calyxes (Hibiscus sabdariffa) in diabetic rats. The present study had, therefore, an objective to investigate the mechanism underlying this activity. Materials and Methods: Male Sprague Dawley rats were induced to be diabetes by intraperitoneal injection of 45 mg/kg streptozotocin (STZ). Normal rats as well as diabetic rats were administered with the ethanolic extract of H. sabdariffa calyxes (HS-EE) at 0.1 and 1.0 g/kg/day, respectively, for 6 weeks. Then, blood glucose and insulin levels, at basal and glucose-stimulated secretions, were measured. The pancreas was dissected to examine histologically. Results: HS-EE 1.0 g/kg/day significantly decreased the blood glucose level by 38 ± 12% in diabetic rats but not in normal rats. In normal rats, treatment with 1.0 g/kg HS-EE increased the basal insulin level significantly as compared with control normal rats (1.28 ± 0.25 and 0.55 ± 0.05 ng/ml, respectively). Interestingly, diabetic rats treated with 1.0 g/kg HS-EE also showed a significant increase in basal insulin level as compared with the control diabetic rats (0.30 ± 0.05 and 0.15 ± 0.01 ng/ml, respectively). Concerning microscopic histological examination, HS-EE 1.0 g/kg significantly increased the number of islets of Langerhans in both normal rats (1.2 ± 0.1 and 2.0 ± 0.1 islet number/10 low-power fields (LPF) for control and HS-EE treated group, respectively) and diabetic rats (1.0 ± 0.3 and 3.9 ± 0.6 islet number/10 LPF for control and HS-EE treated group, respectively). Conclusion: The antidiabetic activity of HS-EE may be partially mediated via the stimulating effect on insulin secretion. PMID:23798879

  2. Predicting above normal wildfire activity in southern Europe as a function of meteorological drought

    International Nuclear Information System (INIS)

    Gudmundsson, L; Seneviratne, S I; Rego, F C; Rocha, M

    2014-01-01

    Wildfires are a recurrent feature of ecosystems in southern Europe, regularly causing large ecological and socio-economic damages. For efficient management of this hazard, long lead time forecasts could be valuable tools. Using logistic regression, we show that the probability of above normal summer wildfire activity in the 1985–2010 time period can be forecasted as a function of meteorological drought with significant predictability (p <0.05) several months in advance. The results show that long lead time forecasts of this natural hazard are feasible in southern Europe, which could potentially aid decision-makers in the design of strategies for forest management. (letter)

  3. X-ray photographs of a solar active region with a multilayer telescope at normal incidence

    Science.gov (United States)

    Underwood, J. H.; Bruner, M. E.; Haisch, B. M.; Brown, W. A.; Acton, L. W.

    1987-01-01

    An astronomical photograph was obtained with a multilayer X-ray telescope. A 4-cm tungsten-carbon multilayer mirror was flown as part of an experimental solar rocket payload, and successful images were taken of the sun at normal incidence at a wavelength of 44 A. Coronal Si XII emission from an active region was recorded on film; as expected, the structure is very similar to that observed at O VIII wavelengths by the Solar Maximum Mission flat-crystal spectrometer at the same time. The small, simple optical system used in this experiment appears to have achieved a resolution of 5 to 10 arcsec.

  4. Proteinase-activated receptors - mediators of early and delayed normal tissue radiation responses

    International Nuclear Information System (INIS)

    Hauer-Jensen, M.

    2003-01-01

    Proteinase-activated receptors (PARs) are G-protein coupled receptors that are activated by proteolytic exposure of a receptor-tethered ligand. The discovery of this receptor family represents one of the most intriguing recent developments in signal transduction. PARs are involved in the regulation of many normal and pathophysiological processes, notably inflammatory and fibroproliferative responses to injury. Preclinical studies performed in our laboratory suggest that proteinase-activated receptor-1 (PAR-1) plays a critical role in the mechanism of chronicity of radiation fibrosis, while proteinase-activated receptor-2 (PAR-2) may mediate important fibroproliferative responses in irradiated intestine. Specifically, activation of PAR-1 by thrombin, and PAR-2 by pancreatic trypsin and mast cell proteinases, appears to be involved in acute radiation-induced inflammation, as well as in subsequent extracellular matrix deposition, leading to the development of intestinal wall fibrosis and clinical complications. Pharmacological modulators of PAR-1 or PAR-2 expression or activation would be potentially useful as preventive or therapeutic agents in patients who receive radiation therapy, especially if blockade could be targeted to specific tissues or cellular compartments

  5. Beta activity in the premotor cortex is increased during stabilized as compared to normal walking

    Directory of Open Access Journals (Sweden)

    Sjoerd M. Bruijn

    2015-10-01

    Full Text Available Walking on two legs is inherently unstable. Still, we humans perform remarkable well at it, mostly without falling. To gain more understanding of the role of the brain in controlling gait stability we measured brain activity using electro-encephalography (EEG during stabilized and normal walking.Subjects walked on a treadmill in two conditions, each lasting 10 minutes; normal, and while being laterally stabilized by elastic cords. Kinematics of trunk and feet, electro-myography (EMG of neck muscles, as well as 64-channel EEG were recorded. To assess gait stability the local divergence exponent, step width, and trunk range of motion were calculated from the kinematic data. We used independent component analysis to remove movement, EMG, and eyeblink artifacts from the EEG, after which dynamic imaging of coherent sources beamformers were determined to identify cortical sources that showed a significant difference between conditions. Stabilized walking led to a significant increase in gait stability, i.e. lower local divergence exponents. Beamforming analysis of the beta band activity revealed significant sources in bilateral pre-motor cortices. Projection of sensor data on these sources showed a significant difference only in the left premotor area, with higher beta power during stabilized walking, specifically around push-off, although only significant around contralateral push-off. It appears that even during steady gait the cortex is involved in the control of stability.

  6. Effect of norfloxacin and moxifloxacin on melanin synthesis and antioxidant enzymes activity in normal human melanocytes.

    Science.gov (United States)

    Beberok, Artur; Wrześniok, Dorota; Otręba, Michał; Miliński, Maciej; Rok, Jakub; Buszman, Ewa

    2015-03-01

    Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.

  7. Investigating the acute and long-term effects of traumatic brain injury on the immune and fibrinolytic system

    OpenAIRE

    MARIA DAGLAS

    2018-01-01

    Traumatic brain injury is a serious condition that results in long-term disability in most patients. This thesis investigated the early and long-term effects of the immune and fibrinolytic response (blood clot breakdown), and the link between these two systems after brain injury in mice. A unique discovery was that the chronic immune response, over a period of 8 months, directly contributes to a worse outcome after brain injury. We also found gender-specific differences occurring at the early...

  8. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Perides, George; Zhuge, Yuzheng; Lin, Tina; Stins, Monique F; Bronson, Roderick T; Wu, Julian K

    2006-01-01

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg -/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg -/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  9. Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats.

    Science.gov (United States)

    Radhika, P; Annapurna, A; Rao, S Nageswara

    2012-05-01

    A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. A significant (Ppaniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats.

  10. TGF-ß Regulates Cathepsin Activation during Normal and Pathogenic Development.

    Science.gov (United States)

    Flanagan-Steet, Heather; Christian, Courtney; Lu, Po-Nien; Aarnio-Peterson, Megan; Sanman, Laura; Archer-Hartmann, Stephanie; Azadi, Parastoo; Bogyo, Matthew; Steet, Richard A

    2018-03-13

    Cysteine cathepsins play roles during development and disease beyond their function in lysosomal protein turnover. Here, we leverage a fluorescent activity-based probe (ABP), BMV109, to track cysteine cathepsins in normal and diseased zebrafish embryos. Using this probe in a model of mucolipidosis II, we show that loss of carbohydrate-dependent lysosomal sorting alters the activity of several cathepsin proteases. The data support a pathogenic mechanism where TGF-ß signals enhance the proteolytic processing of pro-Ctsk by modulating the expression of chondroitin 4-sulfate (C4-S). In MLII, elevated C4-S corresponds with TGF-ß-mediated increases in chst11 expression. Inhibiting chst11 impairs the proteolytic activation of Ctsk and alleviates the MLII phenotypes. These findings uncover a regulatory loop between TGF-ß signaling and Ctsk activation that is altered in the context of lysosomal disease. This work highlights the power of ABPs to identify mechanisms underlying pathogenic development in living animals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. Polyphenols From Cutch Tree (Acacia catechu Willd.: Normalize In Vitro Oxidative Stress and Exerts Antiproliferative Activity

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2017-10-01

    Full Text Available ABSTRACT Oxidative stress, being the main cause of most of the human diseases, has always been the highlight of research worldwide. This stress can be overcome by administration of natural polyphenols. The Acacia catechu Willd. has many refrences available in Ayurveda as important disease curative plant. Its leaves are investigated for ameliorating oxidative stress in present work. Leaves of A. catechu were extracted with 80% methanol to get methanol extract (AME. It was assessed for antioxidant activity using DPPH, ABTS, CUPRAC, ferric ion reducing, superoxide scavenging and peroxyl radical scavenging assays. DNA protective activity was also investigated using plasmid nicking assay. Further, antiproliferative activity was determined using MTT assay in various human cancer cell lines. The quantification of polyphenols was done by UHPLC analysis. Results confirmed that polyphenols of A. catechu were successful in normalizing oxidative stress. AME was found to be most effective in scavenging ABTS radicals while least effective in scavenging ferric ions. UHPLC analysis showed abundance of ellagic acid, rutin and quercetin in AME. Further, AME showed maximum antiproliferative activity against Hep G2 cancer cells. It is concluded that the polyphenols from A. catechu effectively remediates oxidative stress and hence can be used in curing numerous dreadful diseases.

  12. Effect of CAR activation on selected metabolic pathways in normal and hyperlipidemic mouse livers.

    Science.gov (United States)

    Rezen, Tadeja; Tamasi, Viola; Lövgren-Sandblom, Anita; Björkhem, Ingemar; Meyer, Urs A; Rozman, Damjana

    2009-08-19

    Detoxification in the liver involves activation of nuclear receptors, such as the constitutive androstane receptor (CAR), which regulate downstream genes of xenobiotic metabolism. Frequently, the metabolism of endobiotics is also modulated, resulting in potentially harmful effects. We therefore used 1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) to study the effect of CAR activation on mouse hepatic transcriptome and lipid metabolome under conditions of diet-induced hyperlipidemia. Using gene expression profiling with a dedicated microarray, we show that xenobiotic metabolism, PPARalpha and adipocytokine signaling, and steroid synthesis are the pathways most affected by TCPOBOP in normal and hyperlipidemic mice. TCPOBOP-induced CAR activation prevented the increased hepatic and serum cholesterol caused by feeding mice a diet containing 1% cholesterol. We show that this is due to increased bile acid metabolism and up-regulated removal of LDL, even though TCPOBOP increased cholesterol synthesis under conditions of hyperlipidemia. Up-regulation of cholesterol synthesis was not accompanied by an increase in mature SREBP2 protein. As determined by studies in CAR -/- mice, up-regulation of cholesterol synthesis is however CAR-dependent; and no obvious CAR binding sites were detected in promoters of cholesterogenic genes. TCPOBOP also affected serum glucose and triglyceride levels and other metabolic processes in the liver, irrespective of the diet. Our data show that CAR activation modulates hepatic metabolism by lowering cholesterol and glucose levels, through effects on PPARalpha and adiponectin signaling pathways, and by compromising liver adaptations to hyperlipidemia.

  13. Normal weight children have higher cognitive performance - Independent of physical activity, sleep, and diet.

    Science.gov (United States)

    Hjorth, Mads F; Sørensen, Louise B; Andersen, Rikke; Dyssegaard, Camilla B; Ritz, Christian; Tetens, Inge; Michaelsen, Kim F; Astrup, Arne; Egelund, Niels; Sjödin, Anders

    2016-10-15

    Aside from the health consequences, observational studies indicate that being overweight may also negatively affect cognitive function. However, existing evidence has to a large extent not controlled for the possible confounding effect of having different lifestyles. Therefore, the objective was to examine the independent associations between weight status and lifestyle indicators with cognitive performance in 8-11year old Danish children. The analyses included 828 children (measured in 2011-2012) each having one to three measurement occasions separated by approximately 100days. Dietary intake, physical activity, sedentary time, and sleep duration were measured using dietary records and accelerometers. The Children's Sleep Habits Questionnaire was used to access sleep problems and the Andersen test was carried out to estimate cardio-respiratory fitness (CRF). Weight status (underweight, normal weight, and overweight/obese) was defined according to body mass index and cognitive performance was assessed using the d2-test of attention, a reading test, and a math test. A linear mixed model including a number of fixed and random effects was used to test associations between lifestyle indicators as well as BMI category and cognitive performance. After adjustment for demographics, socioeconomics, and multiple lifestyle indicators, normal weight children had higher cognitive test scores than overweight/obese and underweight children of up to 89% and 48% of expected learning within one school year (Pbreakfast consumption, fewer sleep problems, higher CRF, less total physical activity, more sedentary time, and less light physical activity were associated with higher cognitive performance independently of each other in at least one of the three cognitive tests (Pperformance compared to overweight/obese as well as underweight children, independent of multiple lifestyle indicators. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

    Science.gov (United States)

    Reed, G. L.; Matsueda, G. R.; Haber, E.

    1992-01-01

    Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

  15. Role of plasminogen activator inhibitor type-1 in radiation-induced normal tissues injury

    International Nuclear Information System (INIS)

    Abderrahmani, R.

    2010-01-01

    Radiotherapy is an essential tool for cancer treatment, but there is a balance between benefits and risks related to the use of ionizing radiation: the objective is to deliver a maximum dose to the tumour to destroy or to sterilize it while protecting surrounding normal tissues. Radio-induced damages to normal tissues are therefore a limiting factor when increasing the dose delivered to the tumour. One of the objectives of this research thesis is to bring to the fore a relationship between the initiation of lesions and the development of late damages, more particularly in the intestine, and to identify the involved molecular actors and their inter-connectivity. After a first part presenting ionizing radiation, describing biological effects of ionizing radiation and their use in radiotherapy, presenting the intestine and the endothelium and discussing the intestine radio-sensitivity, discussing the radio-induced intestine damages and radiotherapy-induced complications, and presenting the plasminogen activator inhibitor (PAI-1) and its behaviour in presence of ionizing radiation, two articles are reproduced. The first one addresses the effect of a pharmacological inhibition and of genetic deficiency in PAI-1 on the evolution of radio-induced intestine lesions. The second one discusses the fact that radio-induced PAI-1-related death of endothelial cells determines the severity of early radio-induced intestine lesions

  16. The effect of postural changes on plasma renin activity during normal and pathologic pregnancies.

    Science.gov (United States)

    Brandes, J M; Abramovici, H; Katz, M; Diengott, D; Spindel, A; Kahana, L

    1978-11-01

    A study of the effect of posture on plasma renin activity (PRA) in the third trimester in 27 gravidas revealed a significantly greater increase in PRA in the supine position, compared to the left lateral. The women were classified into 3 groups: normal pregnancy, preeclampsia, intrauterine fetal death. There was no statistical difference in PRA among the 3 groups. It is assumed that the increase of PRA in the supine position was due mainly to mechanical pressure by the gravid uterus on the great vessels (regardless of whether the fetus was dead or alive) and that effective circulatory volume was thus reduced. However, low PRA in the left lateral position in women with preeclampsia seemed to correlate with more severe disease in these women.

  17. Soybean and tempeh total isoflvones improved antioxidant activities in normal and scopolamine-induced rat brain

    Directory of Open Access Journals (Sweden)

    Aliya Ahmad

    2015-11-01

    Full Text Available Objective: To highlight the comparative studies between total isoflavone extracts from soybean and tempeh on the neuronal oxidative stress and antioxidant activities. Methods: The total isoflavones were administered orally for 15 days with 3 selected doses (10, 20 and 40 mg/kg. Piracetam (400 mg/kg, p.o. was used as a standard drug while scopolamine (1 mg/kg, i.p. was used as a drug that promoted amnesia in selected groups. The oxidative markers (thiobarbituric acid reactive substances and nitric oxide were measured in brain homogenate. The antioxidant activities evaluated were catalase, superoxide dismutase, glutathione reductase and glutathione. Results: Our results showed that soybean and tempeh isoflavones significantly improved the levels of catalase, superoxide dismutase, glutathione reductase and glutathione while decreased levels of thiobarbituric acid reactive substances and nitric oxide in both the brain of normal as well as scopolamine-induced animals. Conclusions: Our findings suggested that soybean and tempeh isoflavones could be useful in the management and prevention of age-related neurodegenerative changes including Alzheimer’s disease through its antioxidant activities.

  18. Measurement of activity-weighted size distributions of radon decay products in a normally occupied home

    International Nuclear Information System (INIS)

    Hopke, P.K.; Wasiolek, P.; Montassier, N.; Cavallo, A.; Gadsby, K.; Socolow, R.

    1992-01-01

    In order to assess the exposure of individuals to the presence of indoor radioactivity arising from the decay of radon, an automated, semicontinuous graded screen array system was developed to permit the measurement of the activity-weighted size distributions of the radon progeny in homes. The system has been modified so that the electronics and sampling heads can be separated from the pump by approximately 15 m. The system was placed in the living room of a one-storey house with basement in Princeton, NJ and operated for 2 weeks while the house was occupied by the home owners in their normal manner. One of the house occupants was a cigarette smoker. Radon and potential alpha energy concentration (PAEC) measurements were also made, but condensation nuclei counts were not performed. PAEC values ranged from 23.4 to 461.6 mWL. In the measured activity size distributions, the amount of activity in the 0.5-1.5 nm size range can be considered to be the unattached fraction. The mean value for the 218 Po unattached fraction is 0.217 with a range of 0.054-0.549. The median value for the unattached fraction of PAEC is 0.077 with a range of 0.022-0.178. (author)

  19. Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment.

    Science.gov (United States)

    Vermeij, Anouk; Kessels, Roy P C; Heskamp, Linda; Simons, Esther M F; Dautzenberg, Paul L J; Claassen, Jurgen A H R

    2017-02-01

    Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21 healthy older adults and 14 patients with MCI received five weeks of adaptive computerized working-memory (WM) training. Before and after training, functional Near-Infrared Spectroscopy (fNIRS) was used to assess the hemodynamic response in left and right prefrontal cortex during performance of a verbal n-back task with varying levels of WM load. After training, healthy older adults demonstrated decreased prefrontal activation at high WM load, which may indicate increased processing efficiency. Although MCI patients showed improved behavioral performance at low WM load after training, no evidence was found for training-related changes in prefrontal activation. Whole-group analyses showed that a relatively strong hemodynamic response at low WM load was related to worse behavioral performance, while a relatively strong hemodynamic response at high WM load was related to higher training gain. Therefore, a 'youth-like' prefrontal activation pattern at older age may be associated with better behavioral outcome and cognitive plasticity.

  20. Effects of active music therapy on the normal brain: fMRI based evidence.

    Science.gov (United States)

    Raglio, Alfredo; Galandra, Caterina; Sibilla, Luisella; Esposito, Fabrizio; Gaeta, Francesca; Di Salle, Francesco; Moro, Luca; Carne, Irene; Bastianello, Stefano; Baldi, Maurizia; Imbriani, Marcello

    2016-03-01

    The aim of this study was to investigate the neurophysiological bases of Active Music Therapy (AMT) and its effects on the normal brain. Twelve right-handed, healthy, non-musician volunteers were recruited. The subjects underwent 2 AMT sessions based on the free sonorous-music improvisation using rhythmic and melodic instruments. After these sessions, each subject underwent 2 fMRI scan acquisitions while listening to a Syntonic (SP) and an A-Syntonic (AP) Production from the AMT sessions. A 3 T Discovery MR750 scanner with a 16-channel phased array head coil was used, and the image analysis was performed with Brain Voyager QX 2.8. The listening to SP vs AP excerpts mainly activated: (1) the right middle temporal gyrus and right superior temporal sulcus, (2) the right middle frontal gyrus and in particular the right precentral gyrus, (3) the bilateral precuneus, (4) the left superior temporal sulcus and (5) the left middle temporal gyrus. These results are consistent with the psychological bases of the AMT approach and with the activation of brain areas involved in memory and autobiographical processes, and also in personal or interpersonal significant experiences. Further studies are required to confirm these findings and to explain possible effects of AMT in clinical settings.

  1. The biotechnological potential of fibrinolytic enzymes in the dissolution of endogenous blood thrombi.

    Science.gov (United States)

    Kotb, Essam

    2014-01-01

    Formation of endogenous thrombi in blood vessels is one of the leading causes of death in our modern life. According to data provided by the World Health Organization (WHO) in 2000, heart diseases are responsible for 29% of the total mortality rate in the world. For this, a tremendous amount of research has been done in the area of prevention and treatment of these diseases. The classical therapy of these thrombi relies upon the use of antiplatelets, anticoagulants, or even surgeries. Relatively recently, the fibrinolytic enzymes produced by microorganisms, snakes, earthworms, insects, plants, and other organisms are being successfully used in the treatment of blood clots, especially with regard to the direct dissolving action on fibrin in tandem with less cost and side effects in comparison with the first-generation thrombolytic agents, streptokinase and urokinase. Furthermore, recombinant DNA technology has succeeded in improving and decreasing the undesirable effects of the first generation of enzymes. Recombinant PAs or rt-PAs like alteplase, retelase, saruplase, tenecteplase, lanoteplase, and desmoteplase became available in the drug markets with advantages of less binding loci with PAI-1 to avoid degradation while providing faster and more complete reperfusion in a greater number of patients with less risk of bleeding and intracranial hemorrhage. This review is the first to cover all the natural and recombinant thrombolytic agents used in enzyme therapy. © 2014 American Institute of Chemical Engineers.

  2. THE BACTERICIDAL ACTIVITY OF NORMAL GUINEA PIG SERUM AGAINST LISTERIA MONOCYTOGENES AND ITS INHIBITION BY A LISTERIAL CELL EXTRACT,

    Science.gov (United States)

    Normal guinea pig serum contains bactericidins active against Listeria monocytogenes. The listeriocidal activity of the serum did not increase after...factor. Lysozyme was not implicated in the bactericidal system. It was suggested that the bactericidal activity of guinea pig serum might be due either to

  3. Role of p53–fibrinolytic system cross-talk in the regulation of quartz-induced lung injury

    International Nuclear Information System (INIS)

    Bhandary, Yashodhar P.; Shetty, Shwetha K.; Marudamuthu, Amarnath S.; Fu, Jian; Pinson, Barbara M.; Levin, Jeffrey; Shetty, Sreerama

    2015-01-01

    Silica is the major component of airborne dust generated by wind, manufacturing and/or demolition. Chronic occupational inhalation of silica dust containing crystalline quartz is by far the predominant form of silicosis in humans. Silicosis is a progressive lung disease that typically arises after a very long latency and is a major occupational concern with no known effective treatment. The mechanism of silicosis is not clearly understood. However, silicosis is associated with increased cell death, expression of redox enzymes and pro-fibrotic cytokines and chemokines. Since alveolar epithelial cell (AEC) death and disruption of alveolar fibrinolysis is often associated with both acute and chronic lung injuries, we explored whether p53-mediated changes in the urokinase-type plasminogen activator (uPA) system contributes to silica-induced lung injury. We further sought to determine whether caveolin-1 scaffolding domain peptide (CSP), which inhibits p53 expression, mitigates lung injury associated with exposure to silica. Lung tissues and AECs isolated from wild-type (WT) mice exposed to silica exhibit increased apoptosis, p53 and PAI-1, and suppression of uPA expression. Treatment of WT mice with CSP inhibits PAI-1, restores uPA expression and prevents AEC apoptosis by suppressing p53, which is otherwise induced in mice exposed to silica. The process involves CSP-mediated inhibition of serine-15 phosphorylation of p53 by inhibition of protein phosphatase 2A-C (PP2A-C) interaction with silica-induced caveolin-1 in AECs. These observations suggest that changes in the p53–uPA fibrinolytic system cross-talk contribute to lung injury caused by inhalation of silica dust containing crystalline quartz and is protected by CSP by targeting this pathway. - Highlights: • Chronic exposure to quartz dusts is a major cause of lung injury and silicosis. • The survival of patients with silicosis is bleak due to lack of effective treatments. • This study defines a new role of

  4. Expression and activity of arginase isoenzymes during normal and diabetes-impaired skin repair.

    Science.gov (United States)

    Kämpfer, Heiko; Pfeilschifter, Josef; Frank, Stefan

    2003-12-01

    Within the past years, an important role for nitric oxide (NO) in skin repair has been well defined. As NO is synthesized from L-arginine by NO synthases (NOS), the availability of L-arginine might be one rate-limiting factor of NO production at the wound site. Upon injury, arginase-1 and -2 mRNA, protein, and activity were strongly induced reaching a maximum between day 3 and day 7 postwounding. Immunohistochemistry colocalized both arginases and the inducible NOS (iNOS) at epithelial sites at the margins of the wound. Notably, diabetes-impaired skin repair in leptin-deficient mice (diabetes/diabetes, db/db; and obese/obese, ob/ob) was characterized by an abnormally elevated arginase activity in wound tissue in the absence of an expression of iNOS. Expression analyses demonstrated that arginase-1 contributed to increased arginase activities in impaired repair. Interestingly, an improved healing of chronic wound situations in leptin-supplemented ob/ob mice was strongly associated with an adjustment of the dysregulated expression of L-arginine-converting enzymes: an attenuated iNOS expression was upregulated early in repair and an augmented arginase-1 expression and activity was downregulated in the presence of markedly elevated numbers of macrophages during late repair. These data suggest a coordinated consumption of L-arginine by the NOS and arginase enzymatic pathways at the wound site as a prerequisite for a balanced NO (via iNOS) and polyamine (via arginases) synthesis that drives a normal skin repair.

  5. Changes in rat plasma fibrinolytic factors during long term follow up after whole body irradiation

    International Nuclear Information System (INIS)

    Dudek-Wojciechowska, G.; Dancewicz, A.M.

    1989-01-01

    Rats were whole body irradiated with a dose of 7.0 Gy and then bled at different times after exposure, from 1 day to 12 months; in their plasma the activity of plasmin, the level of plasminogen, the activity of plasminogen activator as well as α 2 -antiplasmin and α 2 -macroglobulin were determined. In comparison to control values obtained in parallel determinations it was found that during the acute phase of radiation disease (up to 30 days after irradiation) the activity of plasmin and the level of plasminogen underwent fluctuation: at the beginning there was an increase, followed by a decrease at later time intervals. There was also a distinct decrease (over 50%) in the activity of plasminogen activator. During the 2 to 4 weeks after exposure the activity of inhibitors was somewhat decreased, especially that of α 2 -macroglobulin. At later periods the level of plasminogen and the activity of plasminogen activator returned to normal but that of plasmin underwent fluctuation again, reaching a significant decrease in activity 6 and 12 months after exposure. At these time points also some decrease in activity of inhibitors was observed, especially in that of α 2 -macroglobulin. 11 refs., 1 fig., 2 tabs. (author)

  6. Mood states, sympathetic activity, and in vivo beta-adrenergic receptor function in a normal population.

    Science.gov (United States)

    Yu, Bum-Hee; Kang, Eun-Ho; Ziegler, Michael G; Mills, Paul J; Dimsdale, Joel E

    2008-01-01

    The purpose of this study was to examine the relationship between mood states and beta-adrenergic receptor function in a normal population. We also examined if sympathetic nervous system activity is related to mood states or beta-adrenergic receptor function. Sixty-two participants aged 25-50 years were enrolled in this study. Mood states were assessed using the Profile of Mood States (POMS). Beta-adrenergic receptor function was determined using the chronotropic 25 dose isoproterenol infusion test. Level of sympathetic nervous system activity was estimated from 24-hr urine norepinephrine excretion. Higher tension-anxiety, depression-dejection, and anger-hostility were related to decreased beta-adrenergic receptor sensitivity (i.e., higher chronotropic 25 dose values), but tension-anxiety was the only remaining independent predictor of beta-adrenergic receptor function after controlling for age, gender, ethnicity, and body mass index (BMI). Urinary norepinephrine excretion was unrelated to either mood states or beta-adrenergic receptor function. These findings replicate previous reports that anxiety is related to decreased (i.e., desensitized) beta-adrenergic receptor sensitivity, even after controlling for age, gender, ethnicity, and body mass index.

  7. Effectiveness of Three Different Walking Prescription Durations on Total Physical Activity in Normal- and Overweight Women

    Directory of Open Access Journals (Sweden)

    Yves Schutz

    2014-08-01

    Full Text Available Objective: While there is a dose-response relationship between physical activity (PA and health benefit, little is known about the effectiveness of different PA prescriptions on total daily PA. Aim: To test, under real-life conditions and using an objective, non-invasive measurement technique (accelerometry, the effect of prescribing additional physical activity (walking only of different durations (30, 60 and 90 min/day on compliance (to the activity prescribed and compensation (to total daily PA. Participants in each group were prescribed 5 sessions of walking per week over 4 weeks. Methods: 55 normal-weight and overweight women (mean BMI 25 ± 5 kg/m2, height 165 ± 1 cm, weight 68 ± 2 kg and mean age 27 ± 1 years were randomly assigned to 3 prescription groups: 30, 60 or 90 min/day PA. Results: Walking duration resulted in an almost linear increase in the number of steps per day during the prescription period from an average of about 10,000 steps per day for the 30-min prescription to about 14,000 for the 90-min prescription. Compliance was excellent for the 30-min prescription but decreased significantly with 60-min and 90-min prescriptions. In parallel, degree of compensation subsequent to exercise increased progressively as length of prescription increased. Conclusion: A 30-min prescription of extra walking 5 times per week was well tolerated. However, in order to increase total PA further, much more than 60 min of walking may need to be prescribed in the majority of individuals. While total exercise ‘volume' increased with prescriptions longer than 30 min, compliance to the prescription decreased and greater compensation was evident.

  8. Examination of the neighborhood activation theory in normal and hearing-impaired listeners.

    Science.gov (United States)

    Dirks, D D; Takayanagi, S; Moshfegh, A; Noffsinger, P D; Fausti, S A

    2001-02-01

    Experiments were conducted to examine the effects of lexical information on word recognition among normal hearing listeners and individuals with sensorineural hearing loss. The lexical factors of interest were incorporated in the Neighborhood Activation Model (NAM). Central to this model is the concept that words are recognized relationally in the context of other phonemically similar words. NAM suggests that words in the mental lexicon are organized into similarity neighborhoods and the listener is required to select the target word from competing lexical items. Two structural characteristics of similarity neighborhoods that influence word recognition have been identified; "neighborhood density" or the number of phonemically similar words (neighbors) for a particular target item and "neighborhood frequency" or the average frequency of occurrence of all the items within a neighborhood. A third lexical factor, "word frequency" or the frequency of occurrence of a target word in the language, is assumed to optimize the word recognition process by biasing the system toward choosing a high frequency over a low frequency word. Three experiments were performed. In the initial experiments, word recognition for consonant-vowel-consonant (CVC) monosyllables was assessed in young normal hearing listeners by systematically partitioning the items into the eight possible lexical conditions that could be created by two levels of the three lexical factors, word frequency (high and low), neighborhood density (high and low), and average neighborhood frequency (high and low). Neighborhood structure and word frequency were estimated computationally using a large, on-line lexicon-based Webster's Pocket Dictionary. From this program 400 highly familiar, monosyllables were selected and partitioned into eight orthogonal lexical groups (50 words/group). The 400 words were presented randomly to normal hearing listeners in speech-shaped noise (Experiment 1) and "in quiet" (Experiment 2) as

  9. Correlation- and covariance-supported normalization method for estimating orthodontic trainer treatment for clenching activity.

    Science.gov (United States)

    Akdenur, B; Okkesum, S; Kara, S; Günes, S

    2009-11-01

    In this study, electromyography signals sampled from children undergoing orthodontic treatment were used to estimate the effect of an orthodontic trainer on the anterior temporal muscle. A novel data normalization method, called the correlation- and covariance-supported normalization method (CCSNM), based on correlation and covariance between features in a data set, is proposed to provide predictive guidance to the orthodontic technique. The method was tested in two stages: first, data normalization using the CCSNM; second, prediction of normalized values of anterior temporal muscles using an artificial neural network (ANN) with a Levenberg-Marquardt learning algorithm. The data set consists of electromyography signals from right anterior temporal muscles, recorded from 20 children aged 8-13 years with class II malocclusion. The signals were recorded at the start and end of a 6-month treatment. In order to train and test the ANN, two-fold cross-validation was used. The CCSNM was compared with four normalization methods: minimum-maximum normalization, z score, decimal scaling, and line base normalization. In order to demonstrate the performance of the proposed method, prevalent performance-measuring methods, and the mean square error and mean absolute error as mathematical methods, the statistical relation factor R2 and the average deviation have been examined. The results show that the CCSNM was the best normalization method among other normalization methods for estimating the effect of the trainer.

  10. Acute hypotensive and diuretic activities of Berberis vulgaris root bark aqueous extract in normal rats

    Directory of Open Access Journals (Sweden)

    Muhammad Ahmed

    2018-03-01

    Full Text Available ABSTRACT The aim of this study is to investigate the effectiveness of intravenous administration of Berberis vulgaris root bark aqueous extract (BRBD on the cardiovascular and renal functions of healthy normotensive rats. The different doses of BRBD 1, 10 and 20 mg/kg were administered intravenously (i.v in normal rats. Blood pressure, diuretic activity and serum renal profile were analyzed. Intravenous injection of BRBD at the different doses of 1, 10 and 20 mg/kg showed a dose-dependent reduction in mean arterial blood pressure (P<0.001. At different doses of 1, 10 and 20 mg/kg, the hypotensive effect remained for more than one hour. Single dose administration of BRBD at doses of 10 and 20 mg/kg caused a significant increase in urine output (P<0.001 as compared to the control rats. Serum renal profile test (albumin, Urea, Uric Acid, creatinine and BUN did not show any significant alteration. The authors conclude that the BRBD is a potent hypotensive and possesses diuretic potential

  11. A pleasant familiar odor influences perceived stress and peripheral nervous system activity during normal aging

    Directory of Open Access Journals (Sweden)

    Pauline eJoussain

    2014-02-01

    Full Text Available Effects of smells on stress have been demonstrated in animals and humans, suggesting that inhaling certain odorants may counteract the negative effects of stress. Because stress plays a key role in cerebral aging, the present study set out to examine whether positive odor effects on perceived stress can be achieved in elderly individuals. To this end, two groups of aged individuals (n=36 women, aged from 55 to 65 years, were tested. The first group was exposed for 5 days to a pleasant and, by end of exposure, familiar odor (exposure odor, whereas the other was exposed to a non-scented control stimulus. Stress and mood states were assessed before and after the 5-day odor exposure period. Psychophysiological markers were also assessed at the end of exposure, in response to the exposure odor and to a new odor. Results revealed that stress on this second exposure was decreased and zygomatic EMG activity was increased specifically in the group previously exposed to the odor (p< 0.05. Taken as a whole, these findings offer a new look at the relationship between perceived stress, olfaction and normal aging, opening up new research perspectives on the effect of olfaction on quality of life and well-being in aged individuals.

  12. Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Deborah L. Harrington

    2017-06-01

    Full Text Available Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI are common in Parkinson’s disease (PD, but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF and regional homogeneity (ReHo, a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex, sensorimotor cortex (primary motor, pre/post-central gyrus, basal ganglia (putamen, caudate, and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a

  13. Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

    Science.gov (United States)

    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2005-09-08

    It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

  14. Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with bacterial meningitis

    NARCIS (Netherlands)

    Weisfelt, Martijn; Determann, Rogier M.; de Gans, Jan; van der Ende, Arie; Levi, Marcel; van de Beek, Diederik; Schultz, Marcus J.

    2007-01-01

    OBJECTIVES: This study investigated levels of coagulation and fibrinolysis factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in relation to development of brain infarction. METHODS: CSF was collected from 92 adults with community-acquired bacterial meningitis, who

  15. Flow cytometric assessment of activation of peripheral blood platelets in dogs with normal platelet count and asymptomatic thrombocytopenia.

    Science.gov (United States)

    Żmigrodzka, M; Guzera, M; Winnicka, A

    2016-01-01

    Platelets play a crucial role in hemostasis. Their activation has not yet been evaluated in healthy dogs with a normal and low platelet count. The aim of this study was to determine the influence of activators on platelet activation in dogs with a normal platelet count and asymptomatic thrombocytopenia. 72 clinically healthy dogs were enrolled. Patients were allocated into three groups. Group 1 consisted of 30 dogs with a normal platelet count, group 2 included 22 dogs with a platelet count between 100 and 200×109/l and group 3 consisted of 20 dogs with a platelet count lower than 100×109/l. Platelet rich-plasma (PRP) was obtained from peripheral blood samples using tripotassium ethylenediaminetetraacetic acid (K3-EDTA) as anticoagulant. Next, platelets were stimulated using phorbol-12-myristate-13-acetate or thrombin, stabilized using procaine or left unstimulated. The expression of CD51 and CD41/CD61 was evaluated. Co-expression of CD41/CD61 and Annexin V served as a marker of platelet activation. The expression of CD41/CD61 and CD51 did not differ between the 3 groups. Thrombin-stimulated platelets had a significantly higher activity in dogs with a normal platelet count than in dogs with asymptomatic thrombocytopenia. Procaine inhibited platelet activity in all groups. In conclusion, activation of platelets of healthy dogs in vitro varied depending on the platelet count and platelet activator.

  16. CD4+ T Cell Activation and Vascular Normalization: Two Sides of the Same Coin?

    Science.gov (United States)

    De Palma, Michele; Jain, Rakesh K

    2017-05-16

    Normalization of tumor blood vessels enhances the infiltration and functions of T cells. Tian et al. (2017) report that effector CD4 + T cells, in turn, support vascular normalization, highlighting intertwined roles for blood vessels and T cells in cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Determination of Elements in Normal and Leukemic Human Whole Blood by Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Brune, D; Frykberg, B; Samsahl, K; Wester, P O

    1961-11-15

    By means of gamma-spectrometry the following elements were simultaneously determined in normal and leukemic human whole blood: Cu, Mn, Zn, Sr, Na, P, Ca, Rb, Cd, Sb, Au, Cs and Fe. Chemical separations were performed according to a group separation method using ion-exchange technique. No significant difference between the concentrations of the elements in normal- and leukemic blood was observed.

  18. Determination of Elements in Normal and Leukemic Human Whole Blood by Neutron Activation Analysis

    International Nuclear Information System (INIS)

    Brune, D.; Frykberg, B.; Samsahl, K.; Wester, P.O.

    1961-11-01

    By means of gamma-spectrometry the following elements were simultaneously determined in normal and leukemic human whole blood: Cu, Mn, Zn, Sr, Na, P, Ca, Rb, Cd, Sb, Au, Cs and Fe. Chemical separations were performed according to a group separation method using ion-exchange technique. No significant difference between the concentrations of the elements in normal- and leukemic blood was observed

  19. Sequence of activation of template biosyntheses in normal and transformed human cells after synchronization with a double thimidine block

    International Nuclear Information System (INIS)

    Alekseev, S.B.; Boikov, P.Ya.; Ebralidze, L.K.; Stepanova, L.G.

    1986-01-01

    The sequences of synthesis of DNA, RNA, and various groups of proteins in normal and transformed human fibroblasts was studied in the first mitotic cycle synchronization of the cells by a double thymidine block. Two peculiarities of the synthesis of acid-soluble histone and acid-insoluble proteins in the normal and transformed cells, were detected: (1) in normal fibroblasts the synthesis of the two groups of proteins is a minimum before DNA replication, and the greatest activity is achieved in the G 2 phase; in transformed cells protein synthesis is a maximum after the removal of the thymine block, while in the G 2 phase it is decreased; (2) in normal fibroblasts the synthesis of acid-insoluble proteins is a maximum before the maximum synthesis of DNA, and that of acid-soluble proteins is a maximum after the maximum of DNA synthesis. The opposite picture is observed in transformed cells. RNA synthesis in normal and transformed cells is activated at the end of the G 2 phase. In normal cells the synthesis of proteins is coupled with the activation of RNA synthesis, while in transformed cells protein synthesis is evidently transferred to the following mitotic cycle. Especially pronounced differences were detected in the expression of certain LMG proteins. Thus, in transformed cells the regulation of the coupling of the template syntheses is modified

  20. Bioluminescence imaging of β cells and intrahepatic insulin gene activity under normal and pathological conditions.

    Directory of Open Access Journals (Sweden)

    Tokio Katsumata

    Full Text Available In diabetes research, bioluminescence imaging (BLI has been applied in studies of β-cell impairment, development, and islet transplantation. To develop a mouse model that enables noninvasive imaging of β cells, we generated a bacterial artificial chromosome (BAC transgenic mouse in which a mouse 200-kbp genomic fragment comprising the insulin I gene drives luciferase expression (Ins1-luc BAC transgenic mouse. BLI of mice was performed using the IVIS Spectrum system after intraperitoneal injection of luciferin, and the bioluminescence signal from the pancreatic region analyzed. When compared with MIP-Luc-VU mice [FVB/N-Tg(Ins1-lucVUPwrs/J] expressing luciferase under the control of the 9.2-kbp mouse insulin I promoter (MIP, the bioluminescence emission from Ins1-luc BAC transgenic mice was enhanced approximately 4-fold. Streptozotocin-treated Ins1-luc BAC transgenic mice developed severe diabetes concomitant with a sharp decline in the BLI signal intensity in the pancreas. Conversely, mice fed a high-fat diet for 8 weeks showed an increase in the signal, reflecting a decrease or increase in the β-cell mass. Although the bioluminescence intensity of the islets correlated well with the number of isolated islets in vitro, the intensity obtained from a living mouse in vivo did not necessarily reflect an absolute quantification of the β-cell mass under pathological conditions. On the other hand, adenovirus-mediated gene transduction of β-cell-related transcription factors in Ins1-luc BAC transgenic mice generated luminescence from the hepatic region for more than 1 week. These results demonstrate that BLI in Ins1-luc BAC transgenic mice provides a noninvasive method of imaging islet β cells and extrapancreatic activity of the insulin gene in the liver under normal and pathological conditions.

  1. Evaluation of the door-to-needle time in patients undergoing fibrinolytic therapy after acute myocardial infarction

    International Nuclear Information System (INIS)

    Jehangir, W.; Daood, M.S.; Khan, M.

    2009-01-01

    Early thrombolysis with fibrinolytic therapy has reduced mortality following acute myocardial infarction (AMI) with the major effect coming from early achievement of infarct-related artery potency. This study was carried out to determine the door-to-needle time in patients undergoing fibrinolytic therapy after acute myocardial infarction and to identify factors associated with a prolonged door-to-needle time. This was a cross sectional study in which patients who were thrombolysed for AMI with streptokinase at Punjab Institute of Cardiology, Lahore, from December 12, 2008 to February 18, 2009 were included. All patients admitted with AMI, who were candidates for fibrinolysis, were included. The time of infarction and time of arrival in hospital was determined with ECG changes and asking from patient and/or relatives. The reasons for delay of arrival were asked from patient and accompanying attendants where possible. A door-to-needle time of <30 min could be achieved in 110 of our 201 patients (54.72%). Mean door-to-needle time was 55.13 (+-71.04) minutes. A door-to-needle time of less than 30 minutes in 54.72% is comparable to most contemporary studies however there is a need to look into factors associated with delay. (author)

  2. Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI.

    Science.gov (United States)

    Dehghani, Payam; Lavoie, Andrea; Lavi, Shahar; Crawford, Jennifer J; Harenberg, Sebastian; Zimmermann, Rodney H; Booker, Jeff; Kelly, Sheila; Cantor, Warren J; Mehta, Shamir R; Bagai, Akshay; Goodman, Shaun G; Cheema, Asim N

    2017-10-01

    Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI. Patients undergoing PCI within 24 hours of tenecteplase (TNK), aspirin, and clopidogrel for STEMI were randomized to receive additional clopidogrel 300 mg followed by 75 mg daily or ticagrelor 180 mg followed by 90 mg twice daily. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline) at 4 and 24 hours post-PCI. The primary end point was PRU ≤208 at 4 hours. A total of 140 patients (74 in ticagrelor and 66 in clopidogrel group) were enrolled. The mean PRU values at baseline were similar for the 2 groups (257.8±52.9 vs 259.5±56.7, P=.85, respectively). Post-PCI, patients on ticagrelor, compared to those on clopidogrel, had significantly lower PRU at 4 hours (78.7±88 vs 193.6±86.5, respectively, PPCI frequently had PRU >208. In this high-risk population, ticagrelor provides more prompt and potent platelet inhibition compared with clopidogrel (Funded by Astra Zeneca; NCT01930591, https://clinicaltrials.gov/ct2/show/NCT01930591). Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Dietary intake and physical activity of normal weight and overweight 6 to 14 year old Swiss children

    NARCIS (Netherlands)

    Aeberli, I.; Kaspar, M.; Zimmermann, M.B.

    2007-01-01

    Principles and questions under study: The prevalence of overweight is increasing in Swiss children, and they are at increased risk for hypertension and insulin resistance. Better understanding of how food intakes and activity patterns differ between overweight and normal weight children is needed to

  4. Return to normal of sup(99m)Tc-plasmin test after deep venous thrombosis and its relationship to vessel wall fibrinolysis

    Energy Technology Data Exchange (ETDEWEB)

    Edenbrandt, C.M.; Hedner, U.; Tengborn, L.; Nilsson, J.; Ohlin, P.

    1986-08-01

    Fourteen patients with deep venous thrombosis (DVT) and a positive sup(99m)Tc-plasmin test were followed up to determine how soon a negative test was obtained. Localization and extension of the thrombi were determined by phlebography. Plasminogen activator activity in vein walls and local fibrinolytic activity after venous occlusion were measured in order to find out what the prerequisites for impaired thrombolysis are. The time required to obtain a negative sup(99m)Tc-plasmin test showed considerable variation, ranging from less than 1 week to more than 6 months. The sup(99m)Tc-plasmin test had returned to normal in 64% of the patients after 6 months. No relationship was found between vessel wall fibrinolysis and time to normalization. Instead, we found an association between the time to normalization of the sup(99m)Tc-plasmin test and the size of the thrombus, according to phlebography, as well as between the time to normalization of the sup(99m)Tc-plasmin test and the extension of leg points with a positive sup(99m)Tc-plasmin test at admission. The finding of abnormal sup(99m)Tc-plasmin test results more than 6 months after acute DVT is of practical importance and warrants caution when evaluating patients with symptoms and signs suggestive of acute recurrent DVT.

  5. Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment

    NARCIS (Netherlands)

    Vermeij, A.; Kessels, R.P.C.; Heskamp, L.; Simons, E.M.F.; Dautzenberg, P.LJ.; Claassen, J.A.H.R.

    2017-01-01

    Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21

  6. Ubiquitous expression of MAKORIN-2 in normal and malignant hematopoietic cells and its growth promoting activity.

    Directory of Open Access Journals (Sweden)

    King Yiu Lee

    Full Text Available Makorin-2 (MKRN2 is a highly conserved protein and yet its functions are largely unknown. We investigated the expression levels of MKRN2 and RAF1 in normal and malignant hematopoietic cells, and leukemia cell lines. We also attempted to delineate the role of MKRN2 in umbilical cord blood CD34+ stem/progenitor cells and K562 cell line by over-expression and inhibition of MKRN2 through lentivirus transduction and shRNA nucleofection, respectively. Our results provided the first evidence on the ubiquitous expression of MKRN2 in normal hematopoietic cells, embryonic stem cell lines, primary leukemia and leukemic cell lines of myeloid, lymphoid, erythroid and megakaryocytic lineages. The expression levels of MKRN2 were generally higher in primary leukemia samples compared with those in age-matched normal BM cells. In all leukemia subtypes, there was no significant correlation between expression levels of MKRN2 and RAF1. sh-MKRN2-silenced CD34+ cells had a significantly lower proliferation capacity and decreased levels of the early stem/progenitor subpopulation (CFU-GEMM compared with control cultures. Over-expression of MKRN2 in K562 cells increased cell proliferation. Our results indicated possible roles of MKRN2 in normal and malignant hematopoiesis.

  7. Human osteoarthritic cartilage is synthetically more active but in culture less vital than normal cartilage

    NARCIS (Netherlands)

    Lafeber, F. P.; van Roy, H.; Wilbrink, B.; Huber-Bruning, O.; Bijlsma, J. W.

    1992-01-01

    The proteoglycan turnover of human osteoarthritic (OA) cartilage was compared to that of normal (N) cartilage. The cartilage was obtained postmortem from human femoral knee condyles. Short term cultures were compared to longterm cultures, and proteoglycan synthesis rate, content and release

  8. Effects of fear of falling and activity restriction on normal and dual task walking in community dwelling older adults.

    Science.gov (United States)

    Donoghue, Orna A; Cronin, Hilary; Savva, George M; O'Regan, Claire; Kenny, Rose Anne

    2013-05-01

    Fear of falling (FOF) is associated with poor physical and psychosocial health and can have debilitating consequences especially when it leads to activity restriction. This study examined whether normal and dual task gait disruptions were independently associated with FOF and activity restriction or if they were fully explained by impaired health status. Data was obtained from The Irish Longitudinal Study on Ageing (TILDA). Community dwelling adults ≥65 years, with a Mini-Mental State Examination score ≥18 and who completed a gait assessment (n=1307) were divided into three groups: no FOF, FOF but no activity restriction (FOF-NAR), FOF with activity restriction (FOF-AR). Physical, psychosocial and cognitive measures were obtained and gait characteristics were assessed using a GAITRite(®) mat during normal and dual task (cognitive) walking. After adjusting for sociodemographics, physical, mental and cognitive health, FOF was associated with reduced gait speed and stride length and increased double support phase and step width in normal and dual task conditions; these changes were most pronounced in those who restrict activities as a result of FOF. These gait changes may be associated with an increased fall risk, however some changes especially increased step width may also reflect positive, compensatory adaptations to FOF. The results also highlight the importance of treating underlying health impairments and preventing the transition from FOF to activity restriction. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Gender differences in body composition, physical activity, eating behavior and body image among normal weight adolescents--an evolutionary approach.

    Science.gov (United States)

    Kirchengast, Sylvia; Marosi, Andrea

    2008-12-01

    Body composition but also physical activity patterns underlie gender typical differences throughout human life. In the present study the body composition of 354 girls and 280 boys ageing between 11 and 18 years originating from Eastern Austria were analyzed using bioelectrical impedance method. Normal weight according to body mass index categories was a strict inclusion criterion. Information regarding physical activity during school and leisure time, daily nutritional habits, subjective body satisfaction and weight control practices were collected by means of a structured and standardized questionnaire. Results of the analyses reveal that--as to be expected--adolescent boys and girls differed significantly in body composition, but also in physical activity patterns. Even normal weight girls exhibited a significantly higher amount of absolute and relative fat mass, whereas normal weight boys showed a significantly higher amount of fat free body mass. Furthermore male adolescents were significantly more physically active than their female counterparts. According to the results of multiple regression analyses physical activity patterns had beside sex an independent influence on body composition parameters during adolescence. In contrast, girls and boys showed only minor differences in nutritional habits and weight control practices. Nutritional habits, body satisfaction and weight control practices were not significantly related to body composition parameters. The observed gender differences in body composition as well as in physical activity patterns are interpreted in an evolutionary sense.

  10. Total body calcium by neutron activation analysis in normals and osteoporotic populations: a discriminator of significant bone mass loss

    International Nuclear Information System (INIS)

    Ott, S.M.; Murano, R.; Lewellen, T.K.; Nelp, W.B.; Chesnut, C.M.

    1983-01-01

    Measurements of total body calcium by neutron activation (TBC) in 94 normal individuals and 86 osteoporotic patients are reported. The ability of TBC to discriminate normal from osteoporotic females was evaluated with decision analysis. Bone mineral content (BMC) by single-photon absorptiometry was also measured. TBC was higher in males (range 826 to 1363 gm vs 537 to 1054 in females) and correlated with height in all normals. In females over age 55 there was a negative correlation with age. Thus, for normals an algorithm was derived to allow comparison between measured TBC and that predicted by sex, age, and height (TBCp). In the 28 normal females over age 55, the TBC was 764 +/- 115 gm vs. 616 +/- 90 in the osteoporotics. In 63 of the osteoporotic females an estimated height, from tibial length, was used to predict TBC. In normals the TBC/TBCp ratio was 1.00 +/- 0.12, whereas in osteoporotic females it was 0.80 +/- 0.12. A receiver operating characteristic curve showed better discrimination of osteoporosis with TBC/TBCp than with wrist BMC. By using Bayes' theorem, with a 25% prevalence of osteoporosis (estimate for postmenopausal women), the posttest probability of disease was 90% when the TBC/TBCp ratio was less than 0.84. The authors conclude that a low TBC/TBCp ratio is very helpful in determining osteoporosis

  11. The effect of tranilast on fibroblast activation protein α (FAP-α expression in normal and keloid fibroblasts in vitro

    Directory of Open Access Journals (Sweden)

    Paweł P. Antończak

    2017-07-01

    Full Text Available Introduction . Tranilast (N-(3’,4’-demethoxycinnamoyl-anthranilic acid is an anti-allergic drug. Its mechanism of action is based on the inhibition of antigen-induced release of chemical mediators from mast cells and basophils. It also reveals antifibroproliferative activities. These properties of tranilast are used in the treatment of hypertrophic scars and keloids. Keloids are characterized by incorrect extracellular matrix components turnover. Fibroblasts derived from keloids reveal overproduction of collagen type I and decreased degradation of extracellular matrix in comparison with normal fibroblasts. Fibroblast activation protein α (FAP-α may play an important role in remodeling of extracellular matrix and the invasive properties of keloids. Objective . In the present study, the effect of tranilast on expression of FAP-α gene and its protein was evaluated in normal human dermal fibroblasts and fibroblasts derived from keloids cultured in vitro . Materials and methods. In the first stage of the study, the influence of tranilast on cell viability was estimated. The second stage of the study included the quantitative evaluation of FAP-α mRNA expression in normal and keloid fibroblasts treated with tranilast. The third stage of the study comprised fibroblast activation protein α expression analysis in the examined cells treated with tranilast. Results and conclusions . The expression of FAP-α gene and fibroblast activation protein α is higher in keloid fibroblasts. Tranilast at concentrations of 3 μM and 30 μM up-regulated mRNA FAP-α expression in normal fibroblasts but did not influence keloid fibroblasts. The drug, at concentrations of 30 μM and 300 μM up-regulated fibroblast activation protein α expression in normal fibroblasts and did not influence keloid fibroblasts. Tranilast antiproliferative effect is not associated with FAP-α expression in keloid fibroblasts.

  12. Normal and abnormal electrical activation of the heart. Imaging patterns obtained by phase analysis of equilibrium cardiac studies

    International Nuclear Information System (INIS)

    Pavel, D.; Byrom, E.; Swiryn, S.; Meyer-Pavel, C.; Rosen, K.

    1981-01-01

    By using a temporal Fourier analysis of gated equilibrium cardiac studies, phase images were obtained. These functional images were analysed qualitatively and quantitatively to determine if specific patterns can be found for normal versus abnormal electrical activation of the heart. The study included eight subjects with normal cardiac function and 24 patients with abnormal electrical activation: eight with left bundle branch block (LBBB), two with right bundle branch block (RBBB), six with Wolff-Parkinson-White syndrome (WPW), one with junctional rhythm, one with spontaneous sustained ventricular tachycardia (VT) (all with normal wall motion), two with chronic transvenous pacemakers, and four with induced sustained VT (all with regional wall motion abnormalities). The results show that the two ventricals have the same mean phase (within +-9 0 ) in normals, but significantly different mean phases in all patients with bundle branch blocks. Of the six WPW patients, three had a distinctive abnormal pattern. The patient with junctional rhythm, those with transvenous pacemakers, and those with VT all had abnormal patterns on the phase image. The phase image is capable of showing differences between patients with electrical activation and a variety of electrical abnormalities. Within the latter category distinct patterns can be associated with each type of abnormality. (author)

  13. Steroid hormones as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1988-01-01

    Glucocorticoid and mineralocorticoid receptors are present in normal epithelial cells of both the small and large intestine and there have also been contentious reports of androgen, oestrogen and progesterone receptors in the epithelium of the normal large intestine. The majority of reports suggest that stimulation of the intestinal glucocorticoid receptors results in increased proliferation of epithelial cells in the small bowel, as does stimulation of androgen receptors and possibly mineralocorticoid receptors. The proliferative response of the normal intestine to oestrogens is difficult to evaluate and that to progestigens appears not to have been reported. Epidemiological studies reveal a higher incidence of bowel cancer in premenopausal women than in men of the same age and yet there is a lower incidence of these tumors in women of higher parity. These findings have been atributted to a variety of non-epithelial gender characteristic such as differences in bile metabolism, colonic bacterial and fecal transit times. In experimental animals, androgens have also been shown to influence carcinogenesis and this could well be attributed to changes in food intake etc. However, many studies have now revealed steroid hormone receptors on colorectal tumor cells and thus a direct effect of the steroid hormones on the epithelium during and after malignant transformation must now be considered.

  14. Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1987-01-01

    The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same

  15. Differences in trace element concentrations between Alzheimer and 'normal' human brain tissue using instrumental neutron activation analysis (INAA)

    International Nuclear Information System (INIS)

    Panayi, A.E.; Spyrou, N.M.

    2001-01-01

    Brain samples obtained from the Netherlands Brain Bank were taken from the superior frontal gyrus, superior parietal gyrus and medial temporal gyrus of 'normal' and Alzheimer's disease subjects in order to determine elemental concentrations and compare elemental composition. Brain samples from the cortex were taken from 18 subjects, eight 'normals' (6 males and 2 females) and eleven with Alzheimer's disease, (1 male and 10 females) and the following elemental concentrations, Na, K, Fe, Zn, Se, Br, Rb, Ag, Cs, Ba, and Eu were determined by instrumental neutron activation analysis (INAA). The element which showed the greatest difference was Br, which was found to be significantly elevated in the cortex of Alzheimer's disease brains as compared to the 'normals' at significance (p < 0.001). (author)

  16. Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells.

    Directory of Open Access Journals (Sweden)

    Clementina Sansone

    Full Text Available Diatoms are an important class of unicellular algae that produce bioactive polyunsaturated aldehydes (PUAs that induce abortions or malformations in the offspring of invertebrates exposed to them during gestation. Here we compare the effects of the PUAs 2-trans,4-trans-decadienal (DD, 2-trans,4-trans-octadienal (OD and 2-trans,4-trans-heptadienal (HD on the adenocarcinoma cell lines lung A549 and colon COLO 205, and the normal lung/brunch epithelial BEAS-2B cell line. Using the viability MTT/Trypan blue assays, we show that PUAs have a toxic effect on both A549 and COLO 205 tumor cells but not BEAS-2B normal cells. DD was the strongest of the three PUAs tested, at all time-intervals considered, but HD was as strong as DD after 48 h. OD was the least active of the three PUAs. The effect of the three PUAs was somewhat stronger for A549 cells. We therefore studied the death signaling pathway activated in A549 showing that cells treated with DD activated Tumor Necrosis Factor Receptor 1 (TNFR1 and Fas Associated Death Domain (FADD leading to necroptosis via caspase-3 without activating the survival pathway Receptor-Interacting Protein (RIP. The TNFR1/FADD/caspase pathway was also observed with OD, but only after 48 h. This was the only PUA that activated RIP, consistent with the finding that OD causes less damage to the cell compared to DD and HD. In contrast, cells treated with HD activated the Fas/FADD/caspase pathway. This is the first report that PUAs activate an extrinsic apoptotic machinery in contrast to other anticancer drugs that promote an intrinsic death pathway, without affecting the viability of normal cells from the same tissue type. These findings have interesting implications also from the ecological viewpoint considering that HD is one of the most common PUAs produced by diatoms.

  17. Normal weight children have higher cognitive performance – Independent of physical activity, sleep, and diet

    DEFF Research Database (Denmark)

    Hjorth, Mads F.; Sørensen, Louise B.; Andersen, Rikke

    2016-01-01

    % of expected learning within one school year (P breakfast consumption, fewer sleep problems, higher CRF, less total physical activity, more sedentary time, and less light physical activity were associated with higher cognitive performance independently of each other in at least one of the three...

  18. Cytidine triphosphate synthase activity and mRNA expression in normal human blood cells

    NARCIS (Netherlands)

    Verschuur, A. C.; van Gennip, A. H.; Muller, E. J.; Voûte, P. A.; Vreken, P.; van Kuilenburg, A. B.

    1999-01-01

    Cytidine triphosphate (CTP) synthase is one of the key enzymes in pyrimidine nucleotide anabolic pathways. The activity of this enzyme is elevated in various malignancies including acute lymphocytic leukemia (ALL). In this study we investigated the activity of CTP synthase in various human blood

  19. Frontopolar and anterior temporal cortex activation in a moral judgment task. Preliminary functional MRI results in normal subjects

    International Nuclear Information System (INIS)

    Moll, Jorge; Oliveira-Souza, Ricardo de

    2001-01-01

    The objective was to study the brain areas which are activated when normal subjects make moral judgments. Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either 'right' or 'wrong'. Half of the sentences had an explicit moral content ('We break the law when necessary'), the other half comprised factual statements devoid of moral connotation ('Stones are made of water'). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemo dynamically modeled for event-related f MRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (B A 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct. (author)

  20. Frontopolar and anterior temporal cortex activation in a moral judgment task. Preliminary functional MRI results in normal subjects

    Energy Technology Data Exchange (ETDEWEB)

    Moll, Jorge [LABS and Rede D' Or Hospitais, Rio de Janeiro RJ (Brazil). Grupo de Neuroimagem e Neurologia do Comportamento; Eslinger, Paul J. [Pensylvania State Univ. (United States). College of Medicine. Div. of Neurology and Behavioral Science; The Milton S. Hershey Medical Center, Hershey, PN (United States); Oliveira-Souza, Ricardo de [Universidade do Rio de Janeiro (UNI-Rio), RJ (Brazil). Hospital Universitario Gaffree e Guinle]. E-mail: neuropsychiatry@hotmail.com

    2001-09-01

    The objective was to study the brain areas which are activated when normal subjects make moral judgments. Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either 'right' or 'wrong'. Half of the sentences had an explicit moral content ('We break the law when necessary'), the other half comprised factual statements devoid of moral connotation ('Stones are made of water'). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemo dynamically modeled for event-related f MRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (B A 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct. (author)

  1. Study on cerebral activation areas during repetition with functional MRI in normal adults

    International Nuclear Information System (INIS)

    Koseki, Yohju

    2009-01-01

    For cerebral activation of speech areas in functional MRI (f-MRI) study, the usefulness of an optical microphone, which made it possible to perform task repetition at real time during scanning, was examined. Subjects were 25 healthy adults (mean age, 27.1±5.6 years), who consisted of 15 right-handed and 10 left-handed or ambidextrous persons. Tasks comprised repetition of monosyllables, non-words, words and sentences. The repetition tasks were covertly performed during scanning of f-MRI by using an optical microphone. In both the right-handed and non-right-handed groups, activations in the left superior temporal gyrus (sensory speech area) were most frequently observed during all of the tasks. In the right-handed group, activations in the left inferior frontal (motor speech area) and superior temporal gyri were significantly more often observed than those in the right inferior frontal and superior temporal gyri. From an assessment of the laterality index (LI), left-side dominant activation was frequently seen in most of the cerebral regions including sensory and motor speech areas, although right-side and bilateral dominant activations were observed in a few cases. In both groups, activations in regions associated with sensory speech were significantly more often seen than those in regions associated with motor speech. The present predominant activations in regions involved in sensory speech indicate that the optical microphone is useful in f-MRI studies using task repetition. (author)

  2. Aldosterone breakthrough with benazepril in furosemide-activated renin-angiotensin-aldosterone system in normal dogs.

    Science.gov (United States)

    Lantis, A C; Ames, M K; Atkins, C E; DeFrancesco, T C; Keene, B W; Werre, S R

    2015-02-01

    Pilot studies in our laboratory revealed that furosemide-induced renin-angiotensin-aldosterone system (RAAS) activation was not attenuated by the subsequent co-administration of benazepril. This study was designed to evaluate the effect of benazepril on angiotensin-converting enzyme (ACE) activity and furosemide-induced circulating RAAS activation. Our hypothesis was that benazepril suppression of ACE activity would not suppress furosemide-induced circulating RAAS activation, indicated by urinary aldosterone concentration. Ten healthy hound dogs were used in this study. The effect of furosemide (2 mg/kg p.o., q12h; Group F; n = 5) and furosemide plus benazepril (1 mg/kg p.o., q24h; Group FB; n = 5) on circulating RAAS was determined by plasma ACE activity, 4-6 h posttreatment, and urinary aldosterone to creatinine ratio (UAldo:C) on days -1, -2, 1, 3, and 7. There was a significant increase in the average UAldo:C (μg/g) after the administration of furosemide (Group F baseline [average of days -1 and -2] UAldo:C = 0.41, SD 0.15; day 1 UAldo:C = 1.1, SD 0.56; day 3 UAldo:C = 0.85, SD 0.50; day 7 UAldo:C = 1.1, SD 0.80, P Benazepril suppressed ACE activity (U/L) in Group FB (Group FB baseline ACE = 16.4, SD 4.2; day 1 ACE = 3.5, SD 1.4; day 3 ACE = 1.6, SD 1.3; day 7 ACE = 1.4, SD 1.4, P Benazepril decreased plasma ACE activity but did not prevent furosemide-induced RAAS activation, indicating aldosterone breakthrough (escape). This is particularly noteworthy in that breakthrough is observed at the time of initiation of RAAS suppression, as opposed to developing after months of therapy. © 2014 John Wiley & Sons Ltd.

  3. An assessment of the relationship of physical activity, obesity, and chronic diseases/conditions between active/obese and sedentary/ normal weight American women in a national sample.

    Science.gov (United States)

    Pharr, J R; Coughenour, C A; Bungum, T J

    2018-03-01

    Obesity and physical inactivity are associated with increased rates of chronic diseases and conditions. However, the 'fit but fat' theory posits that cardiopulmonary fitness (or physical activity) can mitigate risks to health associated with obesity. The purpose of this study was to compare chronic diseases and conditions of highly active/obese women with inactive/normal weight women. This was a cross-sectional study of the 2015 Behavioral Risk Factor Surveillance System data. Weighted descriptive statistics were performed to describe the demographic characteristics of the two groups. We calculated odds ratios and adjusted odds ratios for chronic diseases and conditions comparing highly active/obese women with inactive/normal weight women. Highly active/obese women were more likely to report risk factors (hypertension, high cholesterol, and diabetes) for coronary heart disease (CHD) and cardiovascular disease (CVD) than inactive/normal weight women; however, they did not have increased rates of CVD, CHD, or heart attack and had decreased risk for stroke. Highly active/obese women had increased risk for asthma, arthritis, and depression, but not for cancer, kidney disease, or chronic obstructive pulmonary disease. Highly active/obese women appear to be staving off the actual development of CHD and CVD; however, further research is needed to understand the long-term health benefits of physical activity among obese women. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  4. The effects of diet and physical activity on plasma homovanillic acid in normal human subjects.

    Science.gov (United States)

    Kendler, K S; Mohs, R C; Davis, K L

    1983-03-01

    This study examines the effect of diet and moderate physical activity on plasma levels of the dopamine metabolite homovanillic acid (HVA) in healthy young males. At weekly intervals, subjects were fed four isocaloric meals: polycose (pure carbohydrate), sustecal, low monoamine, and high monoamine. Moderate physical activity consisted of 30 minutes of exercise on a bicycle ergometer. The effect of diet on plasma HVA (pHVA) was highly significant. Compared to the polycose meal, the high monoamine meal significantly increased pHVA. Moderate physical activity also significantly increased pHVA. Future clinical studies using pHVA in man as an index of brain dopamine function should control for the effects of both diet and physical activity.

  5. Hypoglycemic activity of Cassia javanica Linn. in normal and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Urmila C Kumavat

    2012-01-01

    Full Text Available In present work, one of the ornamentals and medicinally less known plant Cassia javanica has been explored for hypoglycemic potential. It aimed to check the hypoglycemic effect of C. javanica leaves on normal and streptozotocin (STZ-induced diabetic rats by acute and sub-acute studies. Prior to the hypoglycemic study, acute oral toxicity testing of drug was performed. Later, the effects of single and multiple doses of test drug were studied using various parameters. Dried powdered leaf material was used as an oral drug. The preliminary phytochemistry of drug was done by standard qualitative tests. Diabetes was induced in rats by single intraperitoneal injection of STZ. Single and multiple doses of test drug (0.5 g/kg body weight/day were given to normal and diabetic rats. The parameters studied were blood glucose, serum cholesterol, serum triglycerides, and serum proteins. The results of test drug were compared with standard hypoglycemic drug-glibenclamide (0.01 g/kg/day. Statistical analysis was done by ′Student′s ′t′ test′ and one way ANOVA test. In preliminary phytochemistry, antidiabetic compounds were detected. Unlike acute, subacute treatment of test drug showed highly significant reduction (37.62% in blood glucose level of diabetic rats in ten days. This effect was considerably good in comparison with standard drug (63.51%. The test drug and standard drug exhibited insignificant change in the abnormal levels of serum metabolites of diabetic rats. Preclinically, C. javanica was proved to be effective hypoglycemic agent.

  6. Knockdown of GAD67 protein levels normalizes neuronal activity in a rat model of Parkinson's disease

    DEFF Research Database (Denmark)

    Horvath, Lazlo; van Marion, Ingrid; Taï, Khalid

    2011-01-01

    Dopamine depletion of the striatum is one of the hallmarks of Parkinson's disease. The loss of dopamine upregulates GAD67 expression in the striatal projection neurons and causes other changes in the activity of the basal ganglia circuit.......Dopamine depletion of the striatum is one of the hallmarks of Parkinson's disease. The loss of dopamine upregulates GAD67 expression in the striatal projection neurons and causes other changes in the activity of the basal ganglia circuit....

  7. Relative activity of cerebral subcortical gray matter in varying states of attention and awareness in normal subjects and patient studies

    International Nuclear Information System (INIS)

    Cooper, M.; Chen, C.T.; Levy, J.; Wagner, N.; Spire, J.P.; Jacobsen, J.; Meltzer, H.; Metz, J.; Beck, R.N.

    1985-01-01

    An important aspect of the study of brain function involves measurement of the relationships; between activities in the subcortical gray matter of the caudate and of the thalamus; and between these structures and functional cortical areas. The authors have studied these relationships in 22 subjects under different conditions of activation, sleep and sensory deprivation using a PET VI system and F-18-2DG to determine regional cerebral metabolism. Subject activating conditions were maintained throughout the period of equilibration of F-18-2DG and E.E.G.'s were monitored. Multiple tomographic slices of 1-2 million counts were obtained simultaneously with slice separation of 14mm and each plane parallel to the cantho-meatal line. In activated and non-activated awake conditions for normal subjects, left and right thalmus-to-caudate ratios were similar and greater than unity. This relationship was maintained in non-REM sleep, but was reversed and divergent in REM sleep and sensory deprivation; this was also evident in 3/4 narcoleptics awake and asleep in non-REM and REM and 2/3 schizophrenics and affective disorder, subjects. This approach appears to have potential for characterizating normal and disordered regional cerebral function

  8. Biomagnetic and bioelectric detection of gastric slow wave activity in normal human subjects—a correlation study

    International Nuclear Information System (INIS)

    Somarajan, S; Muszynski, N D; Obioha, C; Bradshaw, L A; Richards, W O

    2012-01-01

    We measured gastric slow wave activity simultaneously with a Superconducting Quantum Interference Device (SQUID) magnetometer, mucosal electrodes and cutaneous electrodes in 18 normal human subjects (11 women and 7 men). We processed signals with Fourier spectral analysis and SOBI blind-source separation techniques. We observed a high waveform correlation between the mucosal electromyogram (EMG) and multichannel SQUID magnetogastrogram (MGG). There was a lower waveform correlation between the mucosal EMG and cutaneous electrogastrogram (EGG), but the correlation improved with the application of SOBI. There was also a high correlation between the frequency of the electrical activity recorded in the MGG and in mucosal electrodes (r = 0.97). We concluded that SQUID magnetometers noninvasively record gastric slow wave activity that is highly correlated with the activity recorded by invasive mucosal electrodes. (paper)

  9. Base excision repair activities differ in human lung cancer cells and corresponding normal controls

    DEFF Research Database (Denmark)

    Karahalil, Bensu; Bohr, Vilhelm A; De Souza-Pinto, Nadja C

    2010-01-01

    Oxidative damage to DNA is thought to play a role in carcinogenesis by causing mutations, and indeed accumulation of oxidized DNA bases has been observed in samples obtained from tumors but not from surrounding tissue within the same patient. Base excision repair (BER) is the main pathway...... for the repair of oxidized modifications both in nuclear and mitochondrial DNA. In order to ascertain whether diminished BER capacity might account for increased levels of oxidative DNA damage in cancer cells, the activities of BER enzymes in three different lung cancer cell lines and their non......-cancerous counterparts were measured using oligonucleotide substrates with single DNA lesions to assess specific BER enzymes. The activities of four BER enzymes, OGG1, NTH1, UDG and APE1, were compared in mitochondrial and nuclear extracts. For each specific lesion, the repair activities were similar among the three...

  10. Mitogenic activity of pine cone extracts against cultured splenocytes from normal and tumor-bearing animals.

    Science.gov (United States)

    Kurakata, Y; Sakagami, H; Takeda, M; Konno, K; Kitajima, K; Ichikawa, S; Hata, N; Sato, T

    1989-01-01

    An acidic pine cone extract, Fr. V. of Pinus parviflora Sieb. et Zucc. significantly stimulated DNA synthesis of isolated splenocytes from both mice and rats, but only marginally affected the DNA synthesis of leukemic cell lines. The maximum stimulation level attained by Fr. V slightly exceeded that of plant lectins, whereas much weaker stimulating activity was found in natural and chemically modified antitumor polysaccharides, sialic acid-rich glycoproteins, and polyphenolic compounds such as lignin and tannic acid. In mice with subcutaneously transplanted sarcoma-180, responses of splenocytes against Con A declines in the terminal stage of tumor development, whereas responses against Fr. V remained relatively constant throughout all periods of tumor progression. The suppression of Fr. V activity by acetylation or methylation suggests the importance of the hydroxyl group in the expression of its stimulation activity.

  11. Normal physical activity obliterates the deleterious effects of high-caloric intake

    DEFF Research Database (Denmark)

    Krogh-Madsen, Rikke; Pedersen, Maria; Solomon, Thomas

    2013-01-01

    A high-caloric intake combined with a sedentary lifestyle is an important player in the development of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine if the level of physical activity has impact on the metabolic effects of a high-caloric (+2,000 kcal/day) intake...... function with regard to capacity of attention. In conclusion, we find evidence to support that habitual physical activity may prevent pathophysiological symptoms associated with diet-induced obesity....... visceral fat compared to the active group. Following the two-week period, the inactive group also experienced a poorer glycaemic control, increased endogenous glucose production, decreased hepatic insulin extraction, increased baseline plasma levels of total cholesterol and LDL, and a decreased cognitive...

  12. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

    International Nuclear Information System (INIS)

    Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, D.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-01-01

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  13. Effects of sex and normal aging on regional brain activation during verbal memory performance

    Science.gov (United States)

    Hazlett, Erin A.; Byne, William; Brickman, Adam M.; Mitsis, Effie M.; Newmark, Randall; Haznedar, M. Mehmet; Knatz, Danielle T.; Chen, Amy D.; Buchsbaum, Monte S.

    2010-01-01

    This study examined the main and interactive effects of age and sex on relative glucose metabolic rate (rGMR) within gray matter of 39 cortical Brodmann areas (BAs) and the cingulate gyrus using 18FDG-PET during a verbal memory task in 70 healthy normal adults, aged 20–87 years. Women showed significantly greater age-related rGMR decline in left cingulate gyrus than men (BAs 25, 24, 23, 31, 29). Both groups showed a decline in the anterior cingulate—a neuroanatomical structure that mediates effective cognitive-emotional interactions (BAs 32, 24, 25), while the other frontal regions did not show substantial decline. No sex differences in rGMR were identified within temporal, parietal and occipital lobes. Sex differences were observed for rGMR within subcomponents of the cingulate gyrus with men higher in BA25 and BA29, but lower in BA24 and BA 23 compared to women. For men, better memory performance was associated with greater rGMR in BA24, whereas in women better performance was associated with orbitofrontal-BA12. These results suggest that both age-related metabolic decline and sex differences within frontal regions are more marked in medial frontal and cingulate areas, consistent with some age-related patterns of affective and cognitive change. PMID:19027195

  14. Activation of apoptotic pathway in normal, cancer ovarian cells by epothilone B.

    Science.gov (United States)

    Rogalska, Aneta; Szula, Ewa; Gajek, Arkadiusz; Marczak, Agnieszka; Jóźwiak, Zofia

    2013-09-01

    The epothilones, a new class of microtubule-targeting agents, seem to be a very promising alternative to the current strategy of cancer treatment. We have analyzed the aspects of epothilone B (Epo B) on cellular metabolism of tumor (OV-90) and normal (MM 14) ovarian cells. The observed effects were compared with those of paclitaxel (PTX), which is now a standard for the treatment of ovarian cancer. The results provide direct evidence that Epo B is considerably more cytotoxic to human OV-90 ovarian cancer cells than PTX. We have found, that antitumor efficacy of this new drug is related to its apoptosis-inducing ability, which was confirmed during measurements typical markers of the process. Epo B induced changes in morphology of cells, mitochondrial membrane potential and cytochrome c release. Also a slight increase of the intracellular calcium level was observed. Moreover, we have found that ROS production, stimulated by Epo B, is directly involved in the induction of apoptosis via mitochondrial pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, d.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-09-21

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  16. Early Behavioral Intervention Is Associated with Normalized Brain Activity in Young Children with Autism

    Science.gov (United States)

    Dawson, Geraldine; Jones, Emily J. H.; Merkle, Kristen; Venema, Kaitlin; Lowy, Rachel; Faja, Susan; Kamara, Dana; Murias, Michael; Greenson, Jessica; Winter, Jamie; Smith, Milani; Rogers, Sally J.; Webb, Sara J.

    2012-01-01

    Objective: A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity. Method:…

  17. Changes of cognition and regional cerebral activity during acute hypoglycemia in normal subjects

    DEFF Research Database (Denmark)

    Bie-Olsen, Lise G; Kjaer, Troels W; Pedersen-Bjergaard, Ulrik

    2009-01-01

    cerebral blood flow (rCBF) as a marker of cerebral activity. Hypoglycemia was induced by intravenous insulin infusion in 19 healthy men performing two different cognitive tasks of varying complexity. The hypoglycemic stimulus [plasma glucose 2.2 mmol/liter (0.4)] produced a significant hormonal...

  18. IDENTIFYING RECENT SURFACE MINING ACTIVITIES USING A NORMALIZED DIFFERENCE VEGETATION INDEX (NDVI) CHANGE DETECTION METHOD

    Science.gov (United States)

    Coal mining is a major resource extraction activity on the Appalachian Mountains. The increased size and frequency of a specific type of surface mining, known as mountain top removal-valley fill, has in recent years raised various environmental concerns. During mountainto...

  19. Towards the normalization of cybercrime victimization : A routine activities analysis of cybercrime in europe

    NARCIS (Netherlands)

    Junger, Marianne; Montoya, L.; Hartel, Pieter H.; Heydari, Maliheh

    2017-01-01

    This study investigates the relationships between users' routine activities and socio-economic characteristics and three forms of cybercrime victimization of 1) online shopping fraud, 2) online banking fraud and 3) cyber-attacks (i.e. DDoS attacks). Data from the Eurobarometer, containing a sample

  20. Active normal faults and submarine landslides in the Keelung Shelf off NE Taiwan

    Directory of Open Access Journals (Sweden)

    Ching-Hui Tsai

    2018-01-01

    Full Text Available The westernmost Okinawa Trough back-arc basin is located to the north of the Ryukyu islands and is situated above the northward dipping Ryukyu subducted slab. In the northern continental margin of the Okinawa Trough, the continental slope between the Keelung Valley and the Mein-Hua Submarine Canyon shows a steep angle and future slope failures are expected. The question is how slope failures will proceed? A sudden deep-seated slump or landslide would probably cause local tsunami and hit northern coast of Taiwan. To understand the probable submarine landslides, we conducted multi-channel seismic reflection, sub-bottom profilers, and multi-beam bathymetry surveys off NE Taiwan. Two general trends of shallow crustal faults are observed. The NE-SW trending faults generally follow the main structural trend of the Taiwan mountain belt. These faults are products of inversion tectonics of reverse faults from the former collisional thrust faults to post-collisional normal faults. Another trend of roughly E-W faults is consistent with the current N-S extension of the southern Okinawa Trough. The fault offsets in the eastern portion of the study area are more pronounced. No obvious basal surface of sliding is found beneath the continental margin. We conclude that the movement of the submarine landslides in the Keelung Shelf off northeastern Taiwan could be in a spread type. The submarine landslides mainly occur in the continental slope area and it is more obvious in the east than in the west of the Keelung Shelf.

  1. Increased renal alpha-epithelial sodium channel (ENAC) protein and increased ENAC activity in normal pregnancy.

    Science.gov (United States)

    West, Crystal; Zhang, Zheng; Ecker, Geoffrey; Masilamani, Shyama M E

    2010-11-01

    Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. We first used a targeted proteomics approach and found that there were no changes in the protein abundance compared with virgin rats of the β or γ ENaC, type 3 Na(+)/H(+) exchanger (NHE3), bumetanide-sensitive cotransporter (NKCC2), or NaCl cotransporter (NCC) in mid- or late pregnancy. In contrast, we observed marked increases in the abundance of the α-ENaC subunit. The plasma volume increased progressively during pregnancy with the greatest plasma volume being evident in late pregnancy. ENaC inhibition abolished the difference in plasma volume status between virgin and pregnant rats. To determine the in vivo activity of ENaC, we conducted in vivo studies of rats in late pregnancy (days 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (U(Na)V postbenzamil-U(Na)V postvehicle) was markedly increased in late pregnancy, and this difference was abolished by pretreatment with the mineralocorticoid receptor antagonist, eplerenone. These findings demonstrate that the increased α-ENaC subunit of pregnancy is associated with an mineralocorticoid-dependent increase in ENaC activity. Further, we show that ENaC activity is a major contributor of plasma volume status in late pregnancy. These changes are likely to contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.

  2. Comparison of Streptokinase Activity from Streptococcus mutans using Different Substrates

    Directory of Open Access Journals (Sweden)

    Muhammad Anjum Zia*, Rana Faisal, Rao Zahid Abbas1, Gull-e-Faran, Muhammad Kashif Saleemi2 and Junaid Ali Khan3

    2013-01-01

    Full Text Available Streptokinase is a novel bacterial fibrinolytic enzyme that binds and activates plasminogen and is produced by several species of Streptococci. Streptococcus mutans was selected for optimum production of streptokinase using corn steep liquor, molasses, rice polishing and sugarcane bagass in liquid state fermentation. Substrates were applied in different concentrations ranging from 0.1-0.8%. Maximum fibrinolytic activity was observed by 0.3% corn steep liquor, 0.5% molasses and rice polishing and 0.4% by sugarcane bagass. The fibrinolytic activity achieved by fibrin clot lysis method was 5.5, 5.08, 5.16 and 4.75 units using corn steep liquor, molasses, rice polishing and sugarcane bagass, respectively.

  3. Food intake during the normal activity phase prevents obesity and circadian desynchrony in a rat model of night work.

    Science.gov (United States)

    Salgado-Delgado, Roberto; Angeles-Castellanos, Manuel; Saderi, Nadia; Buijs, Ruud M; Escobar, Carolina

    2010-03-01

    Shift work or night work is associated with hypertension, metabolic syndrome, cancer, and other diseases. The cause for these pathologies is proposed to be the dissociation between the temporal signals from the biological clock and the sleep/activity schedule of the night worker. We investigated the mechanisms promoting metabolic desynchrony in a model for night work in rats, based on daily 8-h activity schedules during the resting phase. We demonstrate that the major alterations leading to internal desynchrony induced by this working protocol, flattened glucose and locomotor rhythms and the development of abdominal obesity, were caused by food intake during the rest phase. Shifting food intake to the normal activity phase prevented body weight increase and reverted metabolic and rhythmic disturbances of the shift work animals to control ranges. These observations demonstrate that feeding habits may prevent or induce internal desynchrony and obesity.

  4. Global Bi-ventricular endocardial distribution of activation rate during long duration ventricular fibrillation in normal and heart failure canines.

    Science.gov (United States)

    Luo, Qingzhi; Jin, Qi; Zhang, Ning; Han, Yanxin; Wang, Yilong; Huang, Shangwei; Lin, Changjian; Ling, Tianyou; Chen, Kang; Pan, Wenqi; Wu, Liqun

    2017-04-13

    The objective of this study was to detect differences in the distribution of the left and right ventricle (LV & RV) activation rate (AR) during short-duration ventricular fibrillation (SDVF, 1 min) in normal and heart failure (HF) canine hearts. Ventricular fibrillation (VF) was electrically induced in six healthy dogs (control group) and six dogs with right ventricular pacing-induced congestive HF (HF group). Two 64-electrode basket catheters deployed in the LV and RV were used for global endocardium electrical mapping. The AR of VF was estimated by fast Fourier transform analysis from each electrode. In the control group, the LV was activated faster than the RV in the first 20 s, after which there was no detectable difference in the AR between them. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the posterior LV was activated fastest, while the anterior was slowest. In the HF group, a detectable AR gradient existed between the two ventricles within 3 min of VF, with the LV activating more quickly than the RV. When analyzing the distribution of the AR within the bi-ventricles at 3 min of LDVF, the septum of the LV was activated fastest, while the anterior was activated slowest. A global bi-ventricular endocardial AR gradient existed within the first 20 s of VF but disappeared in the LDVF in healthy hearts. However, the AR gradient was always observed in both SDVF and LDVF in HF hearts. The findings of this study suggest that LDVF in HF hearts can be maintained differently from normal hearts, which accordingly should lead to the development of different management strategies for LDVF resuscitation.

  5. ANGIOTONIN-ACTIVATOR, RENIN- AND ANGIOTONIN-INHIBITOR, AND THE MECHANISM OF ANGIOTONIN TACHYPHYLAXIS IN NORMAL, HYPERTENSIVE, AND NEPHRECTOMIZED ANIMALS.

    Science.gov (United States)

    Page, I H; Helmer, O M

    1940-03-31

    1. Angiotonin does not exert its vasoconstrictor effect in the absence of a substance contained in red blood cells and serum which we have called "angiotonin-activator." A fraction has been separated from blood in which angiotonin-activator is concentrated. It contains little or no reninactivator. 2. Repeated intravenous injections of angiotonin into animals causes the pressor response gradually to lessen and finally to disappear (the phenomenon of tachyphylaxis), but much more slowly than when renin is injected. When the response to angiotonin is abolished, renin also fails to act. Large doses of renin reduce and finally abolish the responsiveness to angiotonin. Exhaustion of renin-activator in the blood abolishes the response to renin without abolishing the response to angiotonin. 3. Blood from animals made tachyphylactic by infusion of angiotonin contains greatly reduced amounts of angiotonin-activator. An inhibitor also appears in the blood. 4. Bilateral nephrectomy prolongs and greatly enhances the rise of arterial pressure following injection of angiotonin and renin. The enhancement reaches a maximum in from 24 to 30 hours after operation. Blood from these animals exhibits greatly increased ability to activate angiotonin and renin when tested in isolated perfused organs. Large amounts of angiotonin are required to reduce the amount of activator in their blood. Renin-activator is simultaneously but little affected. 5. Tranfusion of blood from an animal made tachyphylactic to angiotonin into a nephrectomized dog reduces the response of the latter to angiotonin. Angiotonin when added to the blood of the recipient of the transfusion and perfused through a rabbit's ear also exhibits greatly reduced vasoconstrictor action. 6. Transfusion of normal blood in large amounts into nephrectomized or hypertensive dogs reduces the recipient's response to renin. If renintachyphylaxis is established in the donor, transfusion abolishes the response to renin in the recipient

  6. In-vitro secretion of inhibin-like activity by Sertoli cells from normal and prenatally irradiated immature rats

    International Nuclear Information System (INIS)

    Ultee-van Gessel, A.M.; Leemborg, F.G.; Jong, F.H. de; Molen, H.J. van der

    1986-01-01

    The influence of in-vitro conditions on the production of inhibin by Sertoli cells from 21-day-old normal and prenatally irradiated rat testes was studied by measuring inhibin activity in culture media, using the suppression of the release of FSH from cultured rat pituitary cells. Sertoli cells secreted inhibin-like activity during at least 21 days of culture, and cells cultured at 37 0 C produced significantly more inhibin than those cultured at 32 0 C. The presence of fetal calf serum had no significant effect on inhibin production at 32 0 C, while at 37 0 C the production was decreased. The presence of ovine FSH stimulated inhibin secretion, while inhibin concentrations in Sertoli cell culture media were decreased after the addition of testosterone. Testosterone, added together with ovine FSH, suppressed inhibin secretion when compared with the levels found in the presence of FSH alone. The presence of spermatogenic cells decreased the release of inhibin. From these results it was concluded that both Sertoli cells isolated from normal immature rat testes and those from testes without spermatogenic cells can secrete inhibin-like activity in culture. A number of discrepancies with in-vivo observations was observed. (author)

  7. Physical activity and fitness in 8-year-old overweight and normal weight children and their parents

    Science.gov (United States)

    Karppanen, Anna-Kaisa; Ahonen, Sanna-Mari; Tammelin, Tuija; Vanhala, Marja; Korpelainen, Raija

    2012-01-01

    Objectives To compare the physical fitness and physical activity of 8-year-old overweight children (n =53) to normal weight children (n=65), and to determine whether a significant relationship exists between physical activity of parents and their children. Study design A cross-sectional study. Methods A total of 119 children from Northern Finland were recruited for the study. Waist circumference, height, weight and BMI were measured. Physical activity of the children and their parents was determined with self-administered 7-day recall questionnaires (PAQ-C). Physical fitness of the children was evaluated with 7 items of the EUROFIT-test battery (flamingo balance test, plate tapping, sit-and-reach test, sit-ups, bent arm hang and 10×5 shuttle run). Aerobic capacity of the children was tested with 6-minute walking test. Results Overweigh was related to impaired performance in tests requiring muscle endurance, balance, explosive power of lower extremities, upper body strength and endurance, speed and agility in both genders and aerobic capacity in boys. Physical activity levels of overweight boys (2.41 SD 0.72) were lower than their lean counterparts (2.91 SD 0.64, p=0.004); no such difference was observed in girls (2.53 SD 0.64 vs. 2.59 SD 0.68, p=0.741). Physical activity was significantly associated with better performance in several physical fitness tests in boys, but not in girls. Mothers’ physical activity was associated with children's physical activity (r=0.363, pphysical fitness in children. Mother-child relationship of physical activity appeared to be stronger than father-child relationship. Improving physical fitness in children through physical activity might require interventions that are responsive to the ability and needs of overweight children and their families and focus on helping parents and children to be physically active together. PMID:22456036

  8. Accelerometer profiles of physical activity and inactivity in normal weight, overweight, and obese U.S. men and women.

    Science.gov (United States)

    Tudor-Locke, Catrine; Brashear, Meghan M; Johnson, William D; Katzmarzyk, Peter T

    2010-08-03

    The 2005-2006 National Health and Nutrition Examination Survey (NHANES) is used to describe an accelerometer-derived physical activity/inactivity profile in normal weight (BMI /= 30 kg/m2) U.S. adults. We computed physical activity volume indicators (activity counts/day, uncensored and censored steps/day), rate indicators (e.g., steps/minute), time indicators (employing NHANES activity counts/minute cut points to infer time in non-wear, sedentary, low, light, moderate, and vigorous intensities), the number of breaks in sedentary time (occasions when activity counts rose from /= 100 activity counts in the subsequent minute), achievement of public health guidelines, and classification by step-defined physical activity levels. Data were examined for evidence of consistent and significant gradients across BMI-defined categories. In 2005-2006, U.S adults averaged 6,564 +/- SE 107 censored steps/day, and after considering non-wear time, they spent approximately 56.8% of the rest of the waking day in sedentary time, 23.7% in low intensity, 16.7% in light intensity, 2.6% in moderate intensity, and 0.2% in vigorous intensity. Overall, approximately 3.2% of U.S. adults achieved public health guidelines. The normal weight category took 7,190 +/- SE 157 steps/day, and spent 25.7 +/- 0.9 minutes/day in moderate intensity and 7.3 +/- 0.4 minutes/day in vigorous intensity physical activity. The corresponding numbers for the overweight category were 6,879 +/- 140 steps/day, 25.3 +/- 0.9 minutes/day, and 5.3 +/- 0.5 minutes/day and for the obese category 5,784 +/- 124 steps/day, 17.3 +/- 0.7 minutes/day and 3.2 +/- 0.4 minutes/day. Across BMI categories, increasing gradients and significant trends were apparent in males for sedentary time and decreasing gradients and significant trends were evident in time spent in light intensity, moderate intensity, and vigorous intensity. For females, there were only consistent gradients and significant trends apparent for decreasing amounts of

  9. ‘Successful Ageing’ in Practice: Reflections on Health, Activity and Normality in Old Age in Sweden

    Directory of Open Access Journals (Sweden)

    Åsa Alftberg

    2012-11-01

    Full Text Available This article aims to contribute to the critical examination of the notions of health and activity, and to discuss how these cultural and social constructs have impact on elderly people’s lives. An ethnographic perspective gives fruitful inputs to explore how old people deal with the image of old age as one of decay and decline, while they simultaneously relate to the normative idea of so-called successful ageing. The focus is thus on how elderly people create meaning, and how they manage and make use of the contradictory cultural beliefs that are both understood as normality: old age as a passive period of life involving decline and disease, and activity as an individual responsibility in order to stay healthy. The study sample is created with two different methods, qualitative interviews and two different questionnaires, and the majority of the respondents are 65+ years old. The article demonstrates the intersection between old age and a health-promoting active lifestyle. The notion of activity includes moral values, which shape the beliefs and narratives of being old. This forms part of the concept of self-care management, which in old age is also called successful ageing. The idea that activities are health promoting is the framework in which activities are performed, but significance and meaning are rather created from practice.

  10. Activation of Peripheral κ-Opioid Receptors Normalizes Caffeine Effects Modified in Nicotine-Dependent Rats during Nicotine Withdrawal.

    Science.gov (United States)

    Sudakov, S K; Bogdanova, N G

    2016-10-01

    The study examined the effect of peripheral (intragastric) ICI-204,448, an agonist of gastric κ-opioid receptors, on the psychostimulating and anxiolytic effects of caffeine in nicotinedependent rats at the stage of nicotine withdrawal. In these rats, the effects of caffeine (10 mg/kg) were perverted. In nicotine-dependent rats, caffeine produced an anxiolytic effect accompanied by pronounced stimulation of motor activity, in contrast to anxiogenic effect induced by caffeine in intact rats without nicotine dependence. During nicotine withdrawal, nicotine-dependent rats demonstrated enhanced sensitivity to nicotine. Intragastric administration of κ-opioid receptor agonist ICI-204,448 normalized the effect of caffeine in nicotinedependent rats. We have previously demonstrated that activation of peripheral κ-opioid receptors inhibited central κ-opioid activity and eliminated manifestations of nicotine withdrawal syndrome in nicotine-dependent rats, e.g. metabolism activation, stimulation of motor activity, and enhancement of food consumption. In its turn, inhibition of central κ-opioid structures activates the brain adenosine system, which can attenuate the caffeine-induced effects in nicotine-dependent rats.

  11. Dynamics of large-scale brain activity in normal arousal states and epileptic seizures

    Science.gov (United States)

    Robinson, P. A.; Rennie, C. J.; Rowe, D. L.

    2002-04-01

    Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

  12. Benefits of game-based leisure activities in normal aging and dementia.

    Science.gov (United States)

    Narme, Pauline

    2016-12-01

    Given the increasing prevalence of dementia and the limited efficacy of pharmacological treatments, it is crucial to improve the knowledge of the factors that might delay the onset of dementia for developing non-pharmacological interventions. Recent studies have provided evidence that game-based interventions, especially the practice of video games, could improve the cognitive functioning (e.g. executive functions) in older adults and in demented patients. The positive effects of these games have also been demonstrated on physical health (e.g. improvement of balance and gait). Video gamed-based interventions may also alleviate mood or behavioral disorders, and increase interactions with friends, family, caregivers or other patients. The positive impact of games on these domains (cognitive and physical decline, social isolation) suggests that game-based interventions might contribute to delay the onset of dementia. Thus, playing games might be considered as a protective factor in dementia and even more as a potential non-pharmacological strategy in dementia rather than leisure activity.

  13. Ameloblasts require active RhoA to generate normal dental enamel.

    Science.gov (United States)

    Xue, Hui; Li, Yong; Everett, Eric T; Ryan, Kathleen; Peng, Li; Porecha, Rakhee; Yan, Yan; Lucchese, Anna M; Kuehl, Melissa A; Pugach, Megan K; Bouchard, Jessica; Gibson, Carolyn W

    2013-08-01

    RhoA plays a fundamental role in regulation of the actin cytoskeleton, intercellular attachment, and cell proliferation. During amelogenesis, ameloblasts (which produce the enamel proteins) undergo dramatic cytoskeletal changes and the RhoA protein level is up-regulated. Transgenic mice were generated that express a dominant-negative RhoA transgene in ameloblasts using amelogenin gene-regulatory sequences. Transgenic and wild-type (WT) molar tooth germs were incubated with sodium fluoride (NaF) or sodium chloride (NaCl) in organ culture. Filamentous actin (F-actin) stained with phalloidin was elevated significantly in WT ameloblasts treated with NaF compared with WT ameloblasts treated with NaCl or with transgenic ameloblasts treated with NaF, thereby confirming a block in the RhoA/Rho-associated protein kinase (ROCK) pathway in the transgenic mice. Little difference in quantitative fluorescence (an estimation of fluorosis) was observed between WT and transgenic incisors from mice provided with drinking water containing NaF. We subsequently found reduced transgene expression in incisors compared with molars. Transgenic molar teeth had reduced amelogenin, E-cadherin, and Ki67 compared with WT molar teeth. Hypoplastic enamel in transgenic mice correlates with reduced expression of the enamel protein, amelogenin, and E-cadherin and cell proliferation are regulated by RhoA in other tissues. Together these findings reveal deficits in molar ameloblast function when RhoA activity is inhibited. © 2013 Eur J Oral Sci.

  14. The Padul normal fault activity constrained by GPS data: Brittle extension orthogonal to folding in the central Betic Cordillera

    Science.gov (United States)

    Gil, Antonio J.; Galindo-Zaldívar, Jesús; Sanz de Galdeano, Carlos; Borque, Maria Jesús; Sánchez-Alzola, Alberto; Martinez-Martos, Manuel; Alfaro, Pedro

    2017-08-01

    The Padul Fault is located in the Central Betic Cordillera, formed in the framework of the NW-SE Eurasian-African plate convergence. In the Internal Zone, large E-W to NE-SW folds of western Sierra Nevada accommodated the greatest NW-SE shortening and uplift of the cordillera. However, GPS networks reveal a present-day dominant E-W to NE-SW extensional setting at surface. The Padul Fault is the most relevant and best exposed active normal fault that accommodates most of the NE-SW extension of the Central Betics. This WSW-wards dipping fault, formed by several segments of up to 7 km maximum length, favored the uplift of the Sierra Nevada footwall away from the Padul graben hanging wall. A non-permanent GPS network installed in 1999 constrains an average horizontal extensional rate of 0.5 mm/yr in N66°E direction. The fault length suggests that a (maximum) 6 magnitude earthquake may be expected, but the absence of instrumental or historical seismic events would indicate that fault activity occurs at least partially by creep. Striae on fault surfaces evidence normal-sinistral kinematics, suggesting that the Padul Fault may have been a main transfer fault of the westernmost end of the Sierra Nevada antiform. Nevertheless, GPS results evidence: (1) shortening in the Sierra Nevada antiform is in its latest stages, and (2) the present-day fault shows normal with minor oblique dextral displacements. The recent change in Padul fault kinematics will be related to the present-day dominance of the ENE-WSW regional extension versus NNW-SSE shortening that produced the uplift and northwestwards displacement of Sierra Nevada antiform. This region illustrates the importance of heterogeneous brittle extensional tectonics in the latest uplift stages of compressional orogens, as well as the interaction of folding during the development of faults at shallow crustal levels.

  15. Insulin receptor binding and tyrosine kinase activity in skeletal muscle from normal pregnant women and women with gestational diabetes

    DEFF Research Database (Denmark)

    Damm, P.; Handberg, A.; Kühl, C.

    1993-01-01

    OBJECTIVE: To ascertain whether the decreased glucose tolerance and insulin resistance found in normal and gestational diabetic pregnancy might be associated with changes in insulin receptor function. METHODS: Eight nonpregnant healthy women (nonpregnant controls), eight healthy pregnant women...... (pregnant controls), and eight women with gestational diabetes were investigated. All were non-obese. Muscle biopsies were obtained from the vastus lateralis muscle, and insulin binding and tyrosine kinase activities in partially purified skeletal muscle insulin receptors were studied. The pregnant controls...... with gestational diabetes compared to nonpregnant controls (P pregnant women did not differ from the other two groups. Postpartum, no differences in insulin binding were found between the groups. Basal and maximal tyrosine kinase activities toward the exogenous substrate poly(Glu4Tyr1) were...

  16. Immunomodulatory activities of different solvent extracts from Tricholoma matsutake (S. Ito et S. Imai) singer (higher basidiomycetes) on normal mice.

    Science.gov (United States)

    Yin, Xiulian; You, Qinghong; Jiang, Zhonghai

    2012-01-01

    The immunomodulatory activities of different solvent extracts from the culinary-medicinal mushroom Tricholoma matsutake were studied in vivo in normal mice. The extracts were prepared using different solvents in an order of increasing polarity. The immunomodulatory activities were investigated by measuring the thymus and spleen index, phagocytic rate of macrophage phagocytosis, delayed-type hypersensitivity, plaque-forming cell, and proliferation of splenocytes. Results demonstrated that water extract (WE) and n-butyl alcohol extract (BAE) of T. matsutake could enhance the immunity of mice significantly compared with the control group. Main components of WE and BAE were polysaccharides, proteins, and flavonoids; we presume that these may be the main immunomodulating and immuno-enhancing agents in T. matsutake.

  17. Uptake of elemental mercury and activity of catalase in rat, hamster, guinea-pig, normal and acatalasemic mice

    International Nuclear Information System (INIS)

    Eide, I.; Syversen, T.L.M.

    1982-01-01

    Uptake of elemental mercury after inhalation (3.5 mg/m 3 ) and the activity of catalase in brain, liver, kidney and blood were investigated in rat, hamster, guinea-pig, and normal and acatalasemic mice. The uptake of mercury in the species investigated varied considerably, being highest in the two strains of mice, followed by rat and hamster, and lowest in the guinea-pig. The uptake seemed to be more dependent on pulmonary ventilation than on the activity of catalase. The two strains of mice were exposed to a wide range of mercury concentrations in air (0.002-3.5 mg/m 3 ). The content of mercury in brain, liver and kidney was linearly dependent on the mercury concentration in the air, whereas in blood this relationship was exponential. At the lower concentraions of mercury in the inhaled air, the mercury level in blood was significantly lower, and in kidney higher in the acatalasemic mice compared to the normal ones. In acatalasemic mice the mercury content in the liver has higher at all concentrations investigated, whereas in brain no difference between the two strains was found. (author)

  18. Normal accidents

    International Nuclear Information System (INIS)

    Perrow, C.

    1989-01-01

    The author has chosen numerous concrete examples to illustrate the hazardousness inherent in high-risk technologies. Starting with the TMI reactor accident in 1979, he shows that it is not only the nuclear energy sector that bears the risk of 'normal accidents', but also quite a number of other technologies and industrial sectors, or research fields. The author refers to the petrochemical industry, shipping, air traffic, large dams, mining activities, and genetic engineering, showing that due to the complexity of the systems and their manifold, rapidly interacting processes, accidents happen that cannot be thoroughly calculated, and hence are unavoidable. (orig./HP) [de

  19. Ash erupted during normal activity at Stromboli (Aeolian Islands, Italy) raises questions on how the feeding system works

    Science.gov (United States)

    D'Oriano, Claudia; Bertagnini, Antonella; Pompilio, Massimo

    2010-05-01

    Normal activity at Stromboli consists of continuous, non-explosive degassing, punctuated by mild explosions at a frequency of about 13 events/h. Each burst, lasting for a few seconds, throws to heights of 100-300 m incandescent scoriae, ash and blocks made of high-porphyritic (HP) degassed magma. During a multidisciplinary experiments on September 2008, ash samples emitted from 18 distinct explosions were collected with the aim of investigating magmatic and volcanic processes occurring in the conduits during the normal Strombolian activity on the basis of ash characterization. The selected samples are representative of the activity of two different craters (SW and NE) during three distinct days. After sieving, about 30 juvenile fragments (from the 0.5-1 mm size interval) were randomly hand-picked from each sample, and then mounted on double-adhesive tape on a glass slide. Single clasts were examined and photographed at the Scanning Electron Microscope (SEM) for identification of clast types, external morphology description and identification of secondary minerals. The same clasts were embedded in epoxy, sectioned and polished for textural and compositional analysis of the groundmass. Preliminary results indicate that Pele's hairs and fluidal, glassy fragments represent the majority (>50 vol%) of the juvenile material together with dense clasts (<30 vol%) in all the analysed samples, while crystals and lithic clasts are less than 20 vol%. Within the juvenile fraction a minor but significant amount of highly vesicular fragments (< 3 vol%) shows glass composition typical of deep-seated, volatile-rich, low-porphyritic (LP) magma. Until now the emission of the LP magma, as highly vesicular pumice, was associated exclusively with high energy explosions (paroxysms) (Bertagnini et al. 1999, Schiavi et al. 2009). The comparison of the morphological and textural features of these LP ash fragments let exclude that they are clasts recycled after the last paroxysm (15 March

  20. 24-h actigraphic monitoring of motor activity, sleeping and eating behaviors in underweight, normal weight, overweight and obese children.

    Science.gov (United States)

    Martoni, Monica; Carissimi, Alicia; Fabbri, Marco; Filardi, Marco; Tonetti, Lorenzo; Natale, Vincenzo

    2016-12-01

    Within a chronobiological perspective, the present study aimed to describe 24 h of sleep-wake cycle, motor activity, and food intake patterns in different body mass index (BMI) categories of children through 7 days of actigraphic recording. Height and weight were objectively measured for BMI calculation in a sample of 115 Italian primary schoolchildren (10.21 ± 0.48 years, 62.61 % females). According to BMI values, 2.60 % were underweight, 61.70 % were of normal weight, 29.60 % were overweight and 6.10 % were obese. Participants wore a wrist actigraph continuously for 7 days to record motor activity and describe sleep-wake patterns. In addition, participants were requested to push the event-marker button of the actigraph each time they consumed food to describe their circadian eating patterns. BMI group differences were found for sleep quantity (i.e. midpoint of sleep and amplitude), while sleep quality, 24-h motor activity and food intake patterns were similar between groups. Regression analyses showed that BMI was negatively predicted by sleep duration on schooldays. BMI was also predicted by motor activity and by food intake frequencies recorded at particular times of day during schooldays and at the weekend. The circadian perspective seems to provide promising insight into childhood obesity, but this aspect needs to be further explored.

  1. Physical activity and fitness in 8-year-old overweight and normal weight children and their parents

    Directory of Open Access Journals (Sweden)

    Anna-Kaisa Karppanen

    2012-03-01

    Full Text Available Objectives: To compare the physical fitness and physical activity of 8-year-old overweight children (n = 53 to normal weight children (n = 65, and to determine whether a significant relationship exists between physical activity of parents and their children. Study design: A cross-sectional study. Methods: A total of 119 children from Northern Finland were recruited for the study. Waist circumference, height, weight and BMI were measured. Physical activity of the children and their parents was determined with self-administered 7-day recall questionnaires (PAQ-C. Physical fitness of the children was evaluated with 7 items of the EUROFIT-test battery (flamingo balance test, plate tapping, sit-and-reach test, sit-ups, bent arm hang and 10×5 shuttle run. Aerobic capacity of the children was tested with 6-minute walking test. Results: Overweigh was related to impaired performance in tests requiring muscle endurance, balance, explosive power of lower extremities, upper body strength and endurance, speed and agility in both genders and aerobic capacity in boys. Physical activity levels of overweight boys (2.41 SD 0.72 were lower than their lean counterparts (2.91 SD 0.64, p = 0.004; no such difference was observed in girls (2.53 SD 0.64 vs. 2.59 SD 0.68, p = 0.741. Physical activity was significantly associated with better performance in several physical fitness tests in boys, but not in girls. Mothers’ physical activity was associated with children's physical activity (r = 0.363, p < 0.001, but no such association was found between fathers and children (r = 0.019, p = 0.864. Conclusion: This study shows an inverse relationship between excess bodyweight and physical fitness in children. Mother-child relationship of physical activity appeared to be stronger than father-child relationship. Improving physical fitness in children through physical activity might require interventions that are responsive to the ability and needs of overweight children and

  2. Natural killer activity and suppressor cells in irradiated mice repopulated with a mixture of cells from normal and 89Sr-treated donors

    International Nuclear Information System (INIS)

    Levy, E.M.; Kumar, V.; Bennett, M.

    1981-01-01

    Mice that have been injected with 89 Sr have fairly normal B and T cell function, but are abnormal in that they lack natural killer (NK) activity and other functions that require an intact bone marrow. These mice also have an increased potential for suppressor cell activity. We had previously shown that spleen cells from 89 Sr-treated mice could transfer low NK activity and increased suppressor cell function to lethally irradiated syngeneic recipients. To investigate the mechanisms involved in perpetuating these defects, groups of normal spleen or bone marrow cells. Recipients were assayed for their NK activity and suppressor cell function 5 to 14 wk later. it was found that the addition of normal cells in the donor inoculum resulted in normal NK activity. This indicates that low NK activity in 89 Sr-treated mice was not due to the presence of a suppressor cell that prevented NK cell generation. It was additionally found that low NK activity in recipient mice could be boosted by interferon inducers. This would indicate that NK activity in the recipients was not due to a lack of interferon-sensitive pre-NK cells. Suppressor cell function in recipient mice depended on the type and number of normal cells in the donor inoculum. Bone marrow cells were very efficient in overcoming the tendency to produce suppressor cells. It took approximately 20 times more normal spleen cells to produce the same results. The implications of these findings are discussed

  3. Overview of the Mechanics of the Active Mai'iu Low Angle Normal Fault (Dayman Dome), Southeastern Papua New Guinea

    Science.gov (United States)

    Little, T. A.; Boulton, C. J.; Webber, S. M.; Mizera, M.; Oesterle, J.; Ellis, S. M.; Norton, K. P.; Wallace, L.; Biemiller, J.; Seward, D.; Boles, A.

    2016-12-01

    The Mai'iu Fault is a corrugated low-angle normal fault (LANF) that has slipped >24 km. It emerges near sea level at 21° N dip, and flattens southward over the dome crest at 3000 m. This reactivated Paleogene suture is slipping at up to 1 cm/year based on previous GPS data and preliminary 10Be cosmogenic nuclide exposure scarp dating. An alignment of microseismicity (Eilon et al. 2015) suggests a dip of 30° N at 15-25 km depth. Pseudotachylites are abundant in lower, mylonitic parts of the footwall. One vein yielded 40Ar/39Ar ages of 1.9-2.2 Ma, implying seismicity at 8-10 km depth at the above slip rate. Widespread, antithetic normal faults in the footwall are attributed to rolling-hinge controlled yielding during exhumation. A single rider block is downfolded into synformal megamullion. Unconformities within this block, and ductile folding and conjugate strike-slip faulting of mylonitic footwall fabrics record prolonged EW shortening and constriction. Many normal and strike-slip faults cut the metabasaltic footwall recording Andersonian stresses and flipping between σ1 and σ2. To exhume the steep faults, the LANF must have remained active despite differential stress being locally high enough to initiate well-oriented faults—relationships that bracket the frictional strength of the LANF. Quantitative XRD on mafic and serpentinitic gouges reveal the Mai'iu fault core is enriched in weak clays corrensite and saponite. Hydrothermal friction experiments were done at effective normal stresses of 30-210 MPa, and temperatures of 50-450oC. At shallow depths (T≤200 oC), clay-rich fault gouges are frictionally weak (μ=0.13-0.15 and 0.20-0.28) and velocity-strengthening. At intermediate depths (T>200 oC), the footwall is frictionally strong (μ=0.71-0.78 and 0.50-0.64) and velocity-weakening. Velocity-strengthening is observed at T≥400 oC. The experiments provide evidence for deep unstable slip, consistent with footwall pseudotachylites and microseismicity at

  4. Analysis of a hundred-years series of magnetic activity indices. III. Is the frequency distribution logarithmo-normal

    International Nuclear Information System (INIS)

    Mayaud, P.N.

    1976-01-01

    Because of the various components of positive conservation existing in the series of aa indices, their frequency distribution is necessarily distorted with respect to any random distribution. However when one takes these various components into account, the observed distribution can be considered as being a logarithmo-normal distribution. This implies that the geomagnetic activity satisfies the conditions of the central limit theorem, according to which a phenomenon which presents such a distribution is due to independent causes whose effects are multiplicative. Furthermore, the distorsion of the frequency distribution caused by the 11-year and 90-year cycles corresponds to a pure attenuation effect; an interpretation by the solar 'coronal holes' is proposed [fr

  5. Epstein-Barr virus (EBV) LMP2A alters normal transcriptional regulation following B-cell receptor activation

    International Nuclear Information System (INIS)

    Portis, Toni; Longnecker, Richard

    2004-01-01

    The latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) is an important mediator of viral latency in infected B-lymphocytes. LMP2A inhibits B-cell receptor (BCR) signaling in vitro and allows for the survival of BCR-negative B cells in vivo. In this study, we compared gene transcription in BCR-activated B cells from non-transgenic and LMP2A Tg6 transgenic mice. We found that the transcriptional induction and down-regulation of many genes that normally occurs in B cells following BCR activation did not occur in B cells from LMP2A Tg6 transgenic mice. Furthermore, LMP2A induced the expression of various transcription factors and genes associated with DNA/RNA metabolism, which may allow for the altered transcriptional regulation observed in BCR-activated B cells from LMP2A Tg6 mice. These results suggest that LMP2A may inhibit the downstream effects of BCR signaling by directly or indirectly altering gene transcription to ensure EBV persistence in infected B cells

  6. Associations of Body Mass Index, Motor Performance, and Perceived Athletic Competence with Physical Activity in Normal Weight and Overweight Children.

    Science.gov (United States)

    Morrison, Kyle M; Cairney, John; Eisenmann, Joe; Pfeiffer, Karin; Gould, Dan

    2018-01-01

    Children who are overweight and obese display lower physical activity levels than normal weight peers. Measures of weight status, perceived motor competence, and motor skill performance have been identified as potential correlates explaining this discrepancy. 1881 children (955 males; 926 females; 9.9 years) were assessed as part of the Physical Health Activity Study Team project. The age, habitual physical activity participation (PAP), body mass index (BMI), socioeconomic status (SES), motor performance (MP), and perceived athletic competence (PAC) of each child included were assessed. Gender-specific linear regression analyses (main effects model) were conducted to identify the percent variance in PAP explained by the following variables: BMI, MP, and PAC. For males, 18.3% of the variance in PAP was explained by BMI, MP, and PAC. PAC explained 17% of the variance, while MP, BMI, and SES only accounted for 0.6%, 0.7%, and 0.5%, respectively. PAC explained 17.5% of PAP variance in females; MP explained 0.8%. BMI, SES, and chronological age were not significant correlates of PAP in girls. An established repertoire of motor skill performance has been seen as a vehicle to PAP in children; however, this study indicates that PAC should not be overlooked in intervention strategies to promote increased PAP.

  7. Associations of Body Mass Index, Motor Performance, and Perceived Athletic Competence with Physical Activity in Normal Weight and Overweight Children

    Directory of Open Access Journals (Sweden)

    Kyle M. Morrison

    2018-01-01

    Full Text Available Children who are overweight and obese display lower physical activity levels than normal weight peers. Measures of weight status, perceived motor competence, and motor skill performance have been identified as potential correlates explaining this discrepancy. 1881 children (955 males; 926 females; 9.9 years were assessed as part of the Physical Health Activity Study Team project. The age, habitual physical activity participation (PAP, body mass index (BMI, socioeconomic status (SES, motor performance (MP, and perceived athletic competence (PAC of each child included were assessed. Gender-specific linear regression analyses (main effects model were conducted to identify the percent variance in PAP explained by the following variables: BMI, MP, and PAC. For males, 18.3% of the variance in PAP was explained by BMI, MP, and PAC. PAC explained 17% of the variance, while MP, BMI, and SES only accounted for 0.6%, 0.7%, and 0.5%, respectively. PAC explained 17.5% of PAP variance in females; MP explained 0.8%. BMI, SES, and chronological age were not significant correlates of PAP in girls. An established repertoire of motor skill performance has been seen as a vehicle to PAP in children; however, this study indicates that PAC should not be overlooked in intervention strategies to promote increased PAP.

  8. Radio metal (169Yb) uptake in normal and tumour cells in vitro. Influence of metabolic cell activity and complex structure

    International Nuclear Information System (INIS)

    Franke, W.G.; Kampf, G.

    1996-01-01

    Trivalent radio metal tracers have been used for tumour imaging and metastatic pain palliation. For better understanding their tumour accumulation, basic model studies of uptake of different 169 Yb complexes into cultured normal and tumour cells were performed. Whereas the uptake of 169 Yb citrate is strongly dependent on the metabolic activity and is not tumour-cell pacific, the uptake of 169 Yb complexed with amino carbonic acid (NTA, EDTA, DTPA) does not correlate to the metabolic activities. These complexes are taken up to a greater amount by the tumour cells (by a factor of about 2). Uptake of both complex types leads to a stable association to cellular compounds, 169 Yb is not releasable by the strong complexing agent DTPA. Protein binding of the 169 Yb complexes shows great influence on their cellular uptake. The bound proportion is no more available,for cellular uptake. The results indicate that i 0 uptake of 169 Yb citrate is an active cellular transport process which i not tumor-specific, ii) the 169 Yb amino carbonic acid complexes show a weak favouring by the tumour cells, iii) different from earlier acceptions the Yb complexes studied are not taken up by the cells in protein-bound form. The structure of the Yb complex is decisive for its protein binding and cellular uptake. (author). 13 refs., 6 figs

  9. Effects of water pH on gamete activation, embryonic development, and larval normality in Prochilodus lineatus

    Directory of Open Access Journals (Sweden)

    Eduardo Antônio Sanches

    2015-08-01

    Full Text Available We investigated the effects of breeding water pH on the spermatic motility, artificial fertilization, and initial development of offspring in curimba, Prochilodus lineatus. After hormonal induction, we conducted gamete activation, artificial fertilization, and embryo incubation in water with pH values of 4.43 ± 0.13, 5.82 ± 0.14, 7.37 ± 0.10, 8.21 ± 0.06, and 9.57 ± 0.16. When the water pH was 6.65, spermatic motility was maintained for ?25.21 s (P < 0.05. The highest fertilization rates (P < 0.05 were obtained when the water pH ranged from 5.82 ± 0.14 to 8.21 ± 0.06, and the highest hatching rates (P < 0.05 were observed when the water pH was 7.37 ± 0.10. A water pH of between 7.37 ± 0.10 and 8.21 ± 0.06 resulted in more complete formation of the perivitelline space (P < 0.05; additionally, embryos incubated in alkaline waters produced a higher percentage of normal larvae (P < 0.05, despite increased mortality levels. Our results indicate that the pH of the water used for gamete activation, artificial oocyte fertilization, and incubation of eggs and larvae of P. lineatus should be ~7, in order to promote successful breeding and normal larval production.

  10. In a rat model of night work, activity during the normal resting phase produces desynchrony in the hypothalamus.

    Science.gov (United States)

    Salgado-Delgado, Roberto; Nadia, Saderi; Angeles-Castellanos, M; Buijs, Ruud M; Escobar, Carolina

    2010-12-01

    Internal synchrony among external cycles and internal oscillators allows adaptation of physiology to cyclic demands for homeostasis. Night work and shift work lead to a disrupted phase relationship between external time cues and internal rhythms, also losing internal coherence among oscillations. This process results in internal desynchrony (ID) in which behavioral, hormonal, and metabolic variables cycle out of phase. It is still not clear whether ID originates at a peripheral or at a central level. In order to determine the possible role of hypothalamic oscillators in ID, we explored with a rat model of "night work" daily rhythms of activity and clock gene expression in the hypothalamus. This study provides evidence that wakefulness and activity during the normal resting phase lead to a shift in the diurnal rhythms of c-Fos and induce a rhythm of PER1 in the arcuate and dorsomedial nucleus of the hypothalamus, both associated with metabolism and regulation of the sleep/wake cycle. Moreover, the number of orexin (ORX)-positive neurons and c-Fos in the perifornical area increased during the working period, suggesting a relevant switch of activity in this brain region induced by the scheduled activity; however, the colocalization of c-Fos in ORX-positive cells was not increased. In contrast, the suprachiasmatic nucleus and the paraventricular nucleus remained locked to the light/dark cycle, resulting in ID in the hypothalamus. Present data suggest that ID occurs already at the level of the first output projections from the SCN, relaying nuclei that transmit temporal signals to other brain areas and to the periphery.

  11. Pursuing Normality

    DEFF Research Database (Denmark)

    Madsen, Louise Sofia; Handberg, Charlotte

    2018-01-01

    implying an influence on whether to participate in cancer survivorship care programs. Because of "pursuing normality," 8 of 9 participants opted out of cancer survivorship care programming due to prospects of "being cured" and perceptions of cancer survivorship care as "a continuation of the disease......BACKGROUND: The present study explored the reflections on cancer survivorship care of lymphoma survivors in active treatment. Lymphoma survivors have survivorship care needs, yet their participation in cancer survivorship care programs is still reported as low. OBJECTIVE: The aim of this study...... was to understand the reflections on cancer survivorship care of lymphoma survivors to aid the future planning of cancer survivorship care and overcome barriers to participation. METHODS: Data were generated in a hematological ward during 4 months of ethnographic fieldwork, including participant observation and 46...

  12. Clarifying Normalization

    Science.gov (United States)

    Carpenter, Donald A.

    2008-01-01

    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  13. Proteomics study of extracellular fibrinolytic proteases from Bacillus licheniformis RO3 and Bacillus pumilus 2.g isolated from Indonesian fermented food

    Science.gov (United States)

    Nur Afifah, Diana; Rustanti, Ninik; Anjani, Gemala; Syah, Dahrul; Yanti; Suhartono, Maggy T.

    2017-02-01

    This paper presents the proteomics study which includes separation, identification and characterization of proteins. The experiment on Indonesian fermented food such as extracellular fibrinolytic protease from Bacillus licheniformis RO3 and Bacillus pumilus 2.g isolated from red oncom and tempeh gembus was conducted. The experimental works comprise the following steps: (1) a combination of one- and two-dimensional electrophoresis analysis, (2) mass spectrometry analysis using MALDI-TOF-MS and (3) investigation using protein database. The result suggested that there were new two protein fractions of B. licheniformis RO3 and three protein fractions of B. pumilus 2.g. These result has not been previously reported.

  14. Investigation of antihyperglycaemic activity of banana (Musa sp. var. Nanjangud rasa bale) pseudostem in normal and diabetic rats.

    Science.gov (United States)

    Ramu, Ramith; Shirahatti, Prithvi S; Zameer, Farhan; Prasad, M N Nagendra

    2015-01-01

    Postprandial hyperglycaemia in diabetes could be ameliorated by inhibiting intestinal α-glucosidases, responsible for starch hydrolysis and its absorption. Different parts of banana have been in use in conventional medicinal formulations since ancient times. Its role as an antihyperglycaemic agent has also been studied. This study was aimed at explaining the mechanism of hypoglycaemic effect by ethanol extract of banana pseudostem (EE). Additionally, studies on the active components involved in the effect have also been attempted. EE significantly inhibited mammalian intestinal α-glucosidases and yeast α-glucosidase (IC50 , 8.11 ± 0.10 µg mL(-1) ). The kinetic studies showed that EE inhibited sucrase, maltase and and p-nitrophenyl-α-d-glucopyranoside hydrolysis by mixed-type inhibition. Further, in vivo studies identified that the oral administration (100-200 mg kg(-1) body weight) of EE significantly suppressed the maltose/glucose-induced postprandial plasma glucose elevation and wielded an antihyperglycaemic effect in normal and alloxan-induced diabetic rats. GC-MS analysis of EE revealed high levels of β-sitosterol (29.62%), stigmasterol (21.91%), campesterol (10.85%) and other compounds. These findings suggest that EE might exert an anti-diabetic effect by inhibition of α-glucosidases from the intestine, in turn suppressing the carbohydrate absorption into the bloodstream. Hence the results extend a foundation to the future prospects of the food-derived enzyme inhibitors in treatment of diabetes. © 2014 Society of Chemical Industry.

  15. Quasiclassical Theory of Spin Imbalance in a Normal Metal-Superconductor Heterostructure with a Spin-Active Interface

    International Nuclear Information System (INIS)

    Shevtsov, O; Löfwander, T

    2014-01-01

    Non-equilibrium phenomena in superconductors have attracted much attention since the first experiments on charge imbalance in the early 1970's. Nowadays a new promising line of research lies at an intersection between superconductivity and spintronics. Here we develop a quasiclassical theory of a single junction between a normal metal and a superconductor with a spin-active interface at finite bias voltages. Due to spin-mixing and spin-filtering effects of the interface a non-equilibrium magnetization (or spin imbalance) is induced at the superconducting side of the junction, which relaxes to zero in the bulk. A peculiar feature of the system is the presence of interface-induced Andreev bound states, which influence the magnitude and the decay length of spin imbalance. Recent experiments on spin and charge density separation in superconducting wires required external magnetic field for observing a spin signal via non-local measurements. Here, we propose an alternative way to observe spin imbalance without applying magnetic field

  16. Effect of physical activity on pulse wave velocity in elderly subjects with normal glucose, prediabetes or Type 2 Diabetes.

    Science.gov (United States)

    Metsämarttila, Erja; Rodilla, Enrique; Jokelainen, Jari; Herrala, Sauli; Leppäluoto, Juhani; Keinänen-Kiukaanniemi, Sirkka; Herzig, Karl-Heinz

    2018-05-23

    Carotid-femoral pulse wave velocity ((cf)PWV) is a measure of arterial stiffness, predicting cardiovascular disease. We hypothesized that the amount of physical activity (PA) is correlated with reduced arterial stiffness in Type 2 diabetic (T2D) subjects. 570 subjects from the 1945 Oulu birth cohort were included in the analysis. (cf)PWV was determined by a non-invasive applanation tonometry. Oral glucose tolerance test was performed and LDL and HDL cholesterol analyzed. PA was registered daily with a wrist-worn acceleration meter for two weeks. (cf)PWV values in subjects with impaired glucose metabolism (IGM) and T2D were higher than in normal glycemic subjects (P < 0.001). PA, fasting and 2 h glucose and HbA1c correlated significantly with (cf)PWV, but HDL or LDL cholesterol did not. The 2 h glucose, heart rate and alcohol consumption in T2D subjects had independent effects on (cf)PWV in multiple regression analysis. T2D and IGM were significantly associated to (cf)PWV. Interestingly, lipids did not have an additional effect on (cf)PWV. Subjects walking more than 10 000 steps/day had 0.2 m/s lower (cf)PWV than those walking less than 6000 steps/day. Presence of T2D, elevated heart rate and alcohol consumption in males were associated with increased aortic stiffening in elderly subjects.

  17. TU-F-12A-02: Quantitative Characterization of Normal Bone Marrow Proliferative Activity with FLT PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Weisse, N; Jeraj, R [Department of Medical Physics, University of Wisconsin, Madison, WI (United States)

    2014-06-15

    Purpose: [F-18]FLT PET is a tool for assessing health of bone marrow by evaluating its proliferative activity. This study establishes a baseline quantitative characterization of healthy marrow proliferation to aid in diagnosis of hematological disease. Methods: 31 patients (20 male, 11 female, 41–76 years) being treated for solid cancers with no history of hematological disease, osseous metastatic disease, or radiation therapy received pre-treatment FLT PET/CT scans. Total bone marrow was isolated from whole body FLT PET images by manually removing organs and applying a standardize uptake value (SUV) threshold of 1.0. Because adult marrow is concentrated in the axial skeleton, quantitative total bone marrow analysis (QTBMA) was used to isolate marrow in the lumbar spine, thoracic spine, sacrum, and pelvis for analysis. SUVmean, SUVmax, and SUVCV were used to quantify bone marrow proliferation. Correlations were explored between SUV and patient characteristics including age, weight, height, and BMI using the Spearman coefficient (ρ). Results: The population-averaged whole-skeleton SUVmean, SUVmax, and SUVCV were 3.0±0.6, 18.4±5.7, and 0.6±0.1, respectively. Uptake values in the axial skeleton were similar to the whole-skeleton demonstrated by SUVmean in the thoracic spine (3.6±0.6), lumbar spine (3.3±0.5), sacrum (3.0±0.6), and pelvis regions (2.8±0.5). Whole-skeleton SUVmax correlated with patient weight (ρ=0.47, p<0.01) and BMI (ρ=0.60, p<0.01), suggesting marrow activity is related to the body's burden. SUV measures in the thoracic spine, lumbar spine, sacrum, and pelvis were negatively correlated with age (ρ:−0.41 to −0.46, p≤0.02). These negative correlations reflect the fact that active marrow in the adult skeleton is localized in the axial skeleton and decreases with age. Conclusions: Normal bone marrow characterizations were determined using FLT

  18. The influence of social activity on regional cerebral blood flow and mental function in the normal aged volunteers

    International Nuclear Information System (INIS)

    Kobayashi, Shotai; Yamaguchi, Shuhei; Katsube, Tomoko; Kitani, Kohaku; Okada, Masanori

    1983-01-01

    The infuence of social activity on regional cerebral blood flow (rCBF) and mental function was studied by Xe133 inhalation method in normal aged volunteers. Subjects: The first group consisted of 33 aged volunteers living in nursing home and exposed to little social stimuli. There were 15 males (mean age of 77 years) and 18 females (77 years). The second group consisted of 49 aged community volunteers who were confirmed socially active. There were 25 males (76 years) and 24 females (72 years). All subjects were healthy persons without a past hitory of cerebral diseases and lung diseases. There were no difference in blood pressure and hematocrit between the two groups. Method: The rCBF was measured by 16-ch-Novo-cerebrograph. Verbal intelligence was evaluated by the Hasegawa Simple Intelligence Scale for Aged. Performance intelligence was evaluated with the Kohs' Block Design Test. Results: 1) The mean rCBF in group I showed significantly lower value than that of group II, especially in the frontotemporal region. The performance intelligence was decreased in group I. However, there were no significant difference in the verbal intelligence between the two groups. 2) The aging effect on rCBF and intelligences was more prominent in group II. 3) In males, hemispheric rCBF of group I decreased bilaterally associated with the decrease of both intelligences. While the left hemispheric rCBF in females was relatively preserved as well as the preservation of verbal intelligence. These results indicate that the social environmental factors may have significant influence to aging of the brain especially in the males. (author)

  19. Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives

    DEFF Research Database (Denmark)

    Petersen, Kresten R.; Christiansen, Erik; Madsbad, Sten

    1999-01-01

    systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after...... randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also...... included. Both compounds increased fasting plasma insulin and reduced S(i) but did not affect S(g). The relationships between S(i) and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We...

  20. Influence of gamma-radiation upon aldolase activity in red blood cells of normal cattle and cattle with genetically conditioned muscle hypertrophy

    International Nuclear Information System (INIS)

    Gabryelak, T.; Leyko, W.; Kolataj, A.

    1979-01-01

    An investigation was conducted on the influence of gamma-radiation upon the activity of aldolase in erythrocytes of three different groups of cattle: normal cattle, doppelenders, halfdoppelenders. The highest aldolase activity was found in the group of normal cattle, it was lower in halfdoppelenders and the lowest in doppelenders. After irradiation of erythrocytes a dose-dependent increase in the activity of aldolase was observed. The erythrocytes of halfdoppelenders were most sensitive to ionizing radiation in the dose-range of 50-100 krads. (author)

  1. In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

    DEFF Research Database (Denmark)

    Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

    2008-01-01

    in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar......BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...

  2. DNA, histones and neutrophil extracellular traps exert anti-fibrinolytic effects in a plasma environment.

    Science.gov (United States)

    Varjú, Imre; Longstaff, Colin; Szabó, László; Farkas, Ádám Zoltán; Varga-Szabó, Veronika Judit; Tanka-Salamon, Anna; Machovich, Raymund; Kolev, Krasimir

    2015-06-01

    In response to various inflammatory stimuli, neutrophils secrete neutrophil extracellular traps (NETs), web-like meshworks of DNA, histones and granular components forming supplementary scaffolds in venous and arterial thrombi. Isolated DNA and histones are known to promote thrombus formation and render fibrin clots more resistant to mechanical forces and tissue-type plasminogen activator (tPA)-induced enzymatic digestion. The present study extends our earlier observations to a physiologically more relevant environment including plasma clots and NET-forming neutrophils. A range of techniques was employed including imaging (scanning electron microscopy (SEM), confocal laser microscopy, and photoscanning of macroscopic lysis fronts), clot permeability measurements, turbidimetric lysis and enzyme inactivation assays. Addition of DNA and histones increased the median fibre diameter of plasma clots formed with 16 nM thrombin from 108 to 121 and 119 nm, respectively, and decreased their permeability constant from 6.4 to 3.1 and 3.7×10(-9) cm(2). Histones effectively protected thrombin from antithrombin-induced inactivation, while DNA inhibited plasminogen activation on the surface of plasma clots and their plasmin-induced resolution by 20 and 40 %, respectively. DNA and histones, as well as NETs secreted by phorbol-myristate-acetate-activated neutrophils, slowed down the tPA-driven lysis of plasma clots and the latter effect could be reversed by the addition of DNase (streptodornase). SEM images taken after complete digestion of fibrin in NET-containing plasma clots evidenced retained NET scaffold that was absent in DNase-treated clots. Our results show that DNA and histones alter the fibrin architecture in plasma clots, while NETs contribute to a decreased lytic susceptibility that can be overcome by DNase.

  3. Mechanical Stability and Fibrinolytic Resistance of Clots Containing Fibrin, DNA, and Histones*

    Science.gov (United States)

    Longstaff, Colin; Varjú, Imre; Sótonyi, Péter; Szabó, László; Krumrey, Michael; Hoell, Armin; Bóta, Attila; Varga, Zoltán; Komorowicz, Erzsébet; Kolev, Krasimir

    2013-01-01

    Neutrophil extracellular traps are networks of DNA and associated proteins produced by nucleosome release from activated neutrophils in response to infection stimuli and have recently been identified as key mediators between innate immunity, inflammation, and hemostasis. The interaction of DNA and histones with a number of hemostatic factors has been shown to promote clotting and is associated with increased thrombosis, but little is known about the effects of DNA and histones on the regulation of fibrin stability and fibrinolysis. Here we demonstrate that the addition of histone-DNA complexes to fibrin results in thicker fibers (increase in median diameter from 84 to 123 nm according to scanning electron microscopy data) accompanied by improved stability and rigidity (the critical shear stress causing loss of fibrin viscosity increases from 150 to 376 Pa whereas the storage modulus of the gel increases from 62 to 82 pascals according to oscillation rheometric data). The effects of DNA and histones alone are subtle and suggest that histones affect clot structure whereas DNA changes the way clots are lysed. The combination of histones + DNA significantly prolongs clot lysis. Isothermal titration and confocal microscopy studies suggest that histones and DNA bind large fibrin degradation products with 191 and 136 nm dissociation constants, respectively, interactions that inhibit clot lysis. Heparin, which is known to interfere with the formation of neutrophil extracellular traps, appears to prolong lysis time at a concentration favoring ternary histone-DNA-heparin complex formation, and DNase effectively promotes clot lysis in combination with tissue plasminogen activator. PMID:23293023

  4. Surface morphology of active normal faults in hard rock: Implications for the mechanics of the Asal Rift, Djibouti

    Science.gov (United States)

    Pinzuti, Paul; Mignan, Arnaud; King, Geoffrey C. P.

    2010-10-01

    Tectonic-stretching models have been previously proposed to explain the process of continental break-up through the example of the Asal Rift, Djibouti, one of the few places where the early stages of seafloor spreading can be observed. In these models, deformation is distributed starting at the base of a shallow seismogenic zone, in which sub-vertical normal faults are responsible for subsidence whereas cracks accommodate extension. Alternative models suggest that extension results from localised magma intrusion, with normal faults accommodating extension and subsidence only above the maximum reach of the magma column. In these magmatic rifting models, or so-called magmatic intrusion models, normal faults have dips of 45-55° and root into dikes. Vertical profiles of normal fault scarps from levelling campaign in the Asal Rift, where normal faults seem sub-vertical at surface level, have been analysed to discuss the creation and evolution of normal faults in massive fractured rocks (basalt lava flows), using mechanical and kinematics concepts. We show that the studied normal fault planes actually have an average dip ranging between 45° and 65° and are characterised by an irregular stepped form. We suggest that these normal fault scarps correspond to sub-vertical en echelon structures, and that, at greater depth, these scarps combine and give birth to dipping normal faults. The results of our analysis are compatible with the magmatic intrusion models instead of tectonic-stretching models. The geometry of faulting between the Fieale volcano and Lake Asal in the Asal Rift can be simply related to the depth of diking, which in turn can be related to magma supply. This new view supports the magmatic intrusion model of early stages of continental breaking.

  5. Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas, acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist

    Science.gov (United States)

    Uchida, Masahiko; Ito, Tetsuhide; Nakamura, Taichi; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Takayanagi, Ryoichi; Jensen, Robert T.

    2014-01-01

    Objectives Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1) in acute/chronic pancreatitis, however the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues, and the effects of CX3CL1 on activated-PSCs. Methods CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues were evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated-PSCs were examined with realtime-PCR, BrdU assays and Western Blotting. Results In normal pancreas, acinar cells expressed CX3CR1 within granule-like-formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal and activated-PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1, did not induce inflammatory-genes expression in activated-PSCs, but induced proliferation. Conclusions CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis and the CX3CR1s are activated. CX3CL1 induces proliferation of activated-PSCs without increasing release of inflammatory-mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSCs proliferation in pancreatitis where CX3CL1 levels are elevated. PMID:24681877

  6. Rhododenol and raspberry ketone impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45.

    Science.gov (United States)

    Kim, Minjeong; Baek, Heung Soo; Lee, Miri; Park, Hyeonji; Shin, Song Seok; Choi, Dal Woong; Lim, Kyung-Min

    2016-04-01

    Rhododenol or rhododendrol (RD, 4-(4-hydroxyphenyl)-2-butanol) occurs naturally in many plants along with raspberry ketone (RK, 4-(4-hydroxyphenyl)-2-butanone), a ketone derivative, which include Nikko maple tree (Acer nikoense) and white birch (Betula platyphylla). De-pigmenting activity of RD was discovered and it was used as a brightening ingredient for the skin whitening cosmetics. Recently, cosmetics containing RD were withdrawn from the market because a number of consumers developed leukoderma, inflammation and erythema on their face, neck and hands. Here, we explored the mechanism underlying the toxicity of RD and RK against melanocytes using B16F10 murine melanoma cells and human primary epidermal melanocytes. Treatment with RD or RK resulted in the decreased cell viability in a dose-dependent manner which appeared from cell growth arrest. Consistently, ROS generation was significantly increased by RD or RK as determined by DCF-enhanced fluorescence. An antioxidant enzyme, glutathione peroxidase was depleted as well. In line with ROS generation, oxidative damages and the arrest of normal cell proliferation, GADD genes (Growth Arrest and DNA Damage) that include GADD45 and GADD153, were significantly up-regulated. Prevention of ROS generation with an anti-oxidant, N-acetylcysteine (NAC) significantly rescued RD and RK-suppressed melanocyte proliferation. Consistently, up-regulation of GADD45 and GADD153 was significantly attenuated by NAC, suggesting that increased ROS and the resultant growth arrest of melanocytes may contribute to RD and RK-induced leukoderma. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Developmental axon stretch stimulates neuron growth while maintaining normal electrical activity, intracellular calcium flux, and somatic morphology.

    Science.gov (United States)

    Loverde, Joseph R; Pfister, Bryan J

    2015-01-01

    Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury.

  8. Developmental Axon Stretch Stimulates Neuron Growth While Maintaining Normal Electrical Activity, Intracellular Calcium Flux, and Somatic Morphology

    Directory of Open Access Journals (Sweden)

    Joseph R Loverde

    2015-08-01

    Full Text Available Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18 % applied over 5 minutes. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25 % strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury.

  9. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.

    2003-01-01

    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for

  10. Single Cell Chemical Cytometry of Akt Activity in Rheumatoid Arthritis and Normal Fibroblast-like Synoviocytes in Response to Tumor Necrosis Factor α.

    Science.gov (United States)

    Mainz, Emilie R; Serafin, D Stephen; Nguyen, Tuong T; Tarrant, Teresa K; Sims, Christopher E; Allbritton, Nancy L

    2016-08-02

    The etiology of rheumatoid arthritis (RA) is poorly understood, and 30% of patients are unresponsive to established treatments targeting tumor necrosis factor α (TNFα). Akt kinase is implicated in TNFα signaling and may act as a barometer of patient responses to biologic therapies. Fluorescent peptide sensors and chemical cytometry were employed to directly measure Akt activity as well as proteolytic activity in individual fibroblast-like synoviocytes (FLS) from RA and normal subjects. The specificity of the peptide reporter was evaluated and shown to be a valid measure of Akt activity in single cells. The effect of TNFα treatment on Akt activity was highly heterogeneous between normal and RA subjects, which was not observable in bulk analyses. In 2 RA subjects, a bimodal distribution of Akt activity was observed, primarily due to a subpopulation (21.7%: RA Subject 5; 23.8%: RA Subject 6) of cells in which >60% of the reporter was phosphorylated. These subjects also possessed statistically elevated proteolytic cleavage of the reporter relative to normal subjects, suggesting heterogeneity in Akt and protease activity that may play a role in the RA-affected joint. We expect that chemical cytometry studies pairing peptide reporters with capillary electrophoresis will provide valuable data regarding aberrant kinase activity from small samples of clinical interest.

  11. Differential binding activity of the transcription factor LIL-Stat in immature and differentiated normal and leukemic myeloid cells

    NARCIS (Netherlands)

    Tuyt, LML; Bregman, K; Lummen, C; Dokter, WHA; Vellenga, E

    1998-01-01

    Cytokines and growth factors induce activation of the family of signal transducers and activators of transcription (Stats) that directly activate gene expression. Recently, constitutively activated Stat1, Stat3, and Stat5 were identified in nuclear extracts of acute myeloid leukemia (AML) patients,

  12. Pharmacokinetics of Active Components From Guhong Injection in Normal and Pathological Rat Models of Cerebral Ischemia: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Li Yu

    2018-05-01

    Full Text Available Background and Objectives: Guhong Injection (GHI is usually administered for the treatment of stroke in clinics. Aceglutamide and hydroxyl safflower yellow A (HSYA are its key ingredients for brain protective effect. To investigate the pharmacokinetics of aceglutamide and HSYA under pathological and normal conditions, the pharmacokinetic parameters and characteristics of middle cerebral artery occlusion (MCAO and normal rats given the same dosage of GHI were studied compared.Methods: 12 SD rats were divided into two groups, namely, MCAO and normal groups. Both groups were treated with GHI in the same dosage. Plasma samples were collected from the jaw vein at different time points and subsequently tested by high-performance liquid chromatography (HPLC.Results: After administration of GHI, both aceglutamide and HSYA were immediately detected in the plasma. Ninety percent of aceglutamide and HSYA was eliminated within 3 h. For aceglutamide, statistically significant differences in the parameters including AUC(0−t, AUC(0−∞, AUMC(0−t, AUMC(0−∞, Cmax (P < 0.01, and Vz (P < 0.05. Meanwhile, compared with the MCAO group, in the normal group, the values of AUC(0−t, AUMC(0−t, VRT(0−t, and Cmax (P < 0.01 for HSYA were significantly higher, whereas the value of MRT(0−t was significantly lower in the normal group.Conclusions: The in vivo trials based on the different models showed that, the pharmacokinetic behaviors and parameters of aceglutamide and HSYA in GHI were completely different. These results suggest that the pathological damage of ischemia-reperfusion has a significant impact on the pharmacokinetic traits of aceglutamide and HSYA.

  13. Effect of virtual reality exercise using the nintendo wii fit on muscle activities of the trunk and lower extremities of normal adults.

    Science.gov (United States)

    Park, Jungseo; Lee, Daehee; Lee, Sangyong

    2014-02-01

    [Purpose] The present study aimed to determine the effect of virtual reality exercise using the Nintendo Wii Fit on the muscle activities of the trunk and lower extremities of normal adults. [Subjects] The subjects of the study were 24 normal adults who were divided into a virtual reality exercise group (VREG, n=12) and a stable surface exercise group (SEG, n=12). [Methods] The exercises of the VREG using the Nintendo Wii Fit and the SEG using a stable surface were conducted three times a week for six weeks. Electromyography was used to measure the muscle activities of the tibialis anterior (TA), medial gastrocnemius (MG), erector spinae (ES), and rectus abdominal (RA) muscles. [Results] VREG showed significant within group differences in TA and MG muscle activities, while the SEG showed a significant difference in the muscle activity of the MG. [Conclusion] Virtual reality exercise using the Nintendo Wii Fit was an effective intervention for the muscle activities of the TA and MG of normal adults.

  14. Correlation between L-Carnitine and alpha-1, 4-glucosidase activity in the semen of normal, infertile and vasectomized men.

    Science.gov (United States)

    Tremblay, R R; Chapdelaine, P; Roy, R; Thabet, M

    1982-01-01

    The semen content of L-carnitine and of alpha 1, 4-glucosidase has been measured in subjects consulting for evaluation of their fertility. A close correlation (r=0.684) was found between both parameters over the range of azoospermia to normal zoospermia. A significant number of patients with oligo or azoospermia displayed normal values of L-carnitine and of alpha-1, 4-glucosidase while approximately 50% showed levels in the low spectrum of vasectomized men. On the basis of these findings, an obstructive pathology at epididymal or vas deferens level was established by vasography and/or bilateral scrotal exploration in 9 patients with azoospermia. These 2 epididymal markers might thus be useful in the hands of the practicing andrologist who has to determine precisely the site of a dysfunction in the reproductive system which leads to infertility.

  15. Does low protein concentration of tissue-type plasminogen activator predict a low risk of spontaneous deep vein thrombosis?

    DEFF Research Database (Denmark)

    Gram, J; Sidelmann, Johannes Jakobsen; Jespersen, J

    1995-01-01

    activity (p Reasonable separation could be obtained for t-PA with a cut-off point of 5...... interval 70%-94%). We observed a significantly negative association between concentration of t-PA and fibrinolytic activity (rs = -0.47; p WORDS)...

  16. Evaluation of the transforming growth factor-beta activity in normal and dry eye human tears by CCL-185 cell bioassay.

    Science.gov (United States)

    Zheng, Xiaofen; De Paiva, Cintia S; Rao, Kavita; Li, De-Quan; Farley, William J; Stern, Michael; Pflugfelder, Stephen C

    2010-09-01

    To develop a new bioassay method using human lung epithelial cells (CCL-185) to assess activity of transforming growth factor beta (TGF-beta) in human tear fluid from normal subjects and patients with dry eye. Two epithelial cell lines, mink lung cells (CCL-64) and human lung cells (CCL-185), were compared to detect the active form of TGF-beta by BrdU incorporation (quantitation of cell DNA synthesis) and WST assay (metabolic activity of viable cells). The effect of TGF-beta on the growth of CCL-185 cells was observed microscopically. Human tears from normal control subjects and patients with dry eye (DE) with and without Sjögren syndrome were evaluated for TGF-beta concentration by Luminex microbead assay, and TGF-beta activity by the CCL-185 cell growth inhibition bioassay. The metabolic activity of viable CCL-185 cells, measured by WST, was shown to be proportional to the TGF-beta1 concentration (R = 0.919) and confirmed by BrdU assay (R = 0.969). Compared with CCL-185, metabolic activity of viable cells and DNA synthesis, measured by WST and BrdU incorporation assays, were shown to be less proportional to the TGF-beta1 concentration in the CCL-64 line (R = 0.42 and 0.17, respectively). Coincubation with human anti-TGF-beta1 antibody (MAB-240) yielded a dose-dependent inhibition of TGF-beta1 (0.3 ng/mL) activity. CCL-185 cell growth observed microscopically was noted to decrease in response to increasing TGF-beta1 concentrations. Levels of immuodetectable TGF-beta1 and TGF-beta2 were similar in normal and DE tears. TGF-beta bioactivity in DE human tears measured by the CCL-185 cells assay was found to be higher (9777.5 +/- 10481.9 pg/mL) than those in normal controls (4129.3 +/- 1342.9 pg/mL) (P tears and 37.6% TGF-beta in normal tears were found to be biologically active. The CCL-185 cell assay was found to be a suitable tool for assessing TGF-beta activity in human tears. Tear TGF-beta bioactivity increases in DE, particularly in Sjögren syndrome, where

  17. Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Lucy M Collins

    2018-02-01

    Full Text Available Background: Recently, the development of Parkinson’s disease (PD has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA mutations. Methods: We investigated PD and Gaucher Disease (GD patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.

  18. Hemostatic profile changes in patients with traumatic brain injury with regard to the genotypes of -675 4G/5G polymorphism of plasminogen activator inhibitor-1 gene

    Directory of Open Access Journals (Sweden)

    O. O. Potapov

    2016-10-01

    Full Text Available Traumatic brain injury (TBI is a significant problem in modern clinical medicine that has both medical and social importance. Analysis of hemostatic changes is a very important aspect of clinical course of TBI and should be paid special attention on it. This analysis is necessary to make prognosis for the treatment outcomes taking into account associations with genetic factors. The aim of research was to analyze hemostatic profile changes in patients with TBI with regard to the genotype of -675 4G/5G polymorphism of plasminogen activator inhibitor-1 gene (РАІ-1. Methods and materials. The research was based on the investigation results of 200 patients with isolated TBI, who were undergoing in-patient treatment at the neurosurgery department at Sumy Regional Clinical Hospital in 2011–2013, and 95 apparently healthy individuals of the control group. The following change cycling was confirmed during the study: a tendency to hypercoagulability on the 1st day transforming into a state of being incapable of coagulation on the 3rd day. On the 7 day hypercoagulability signs dominated and by the 14 day the laboratory findings had gradually become normal. Conclusions. According to the analysis of routine hemostatic profile parameters (activated partial thromboplastin time, prothrombin index, platelet count, plasma tolerance to heparin, activated recalcification time, euglobulin clot lysis assay, plasma fibrinogen level we concluded that there is no association between the studied parameters and the genotypes of the -675 4G/5G polymorphism in the PAI-1 gene in patients with TBI and controls. Our study confirms the necessity of further monitoring of fibrinolytic system, since routine laboratory tests of haemostasis are not always informative as for the fibrinolytic disorders in patients with TBI.

  19. Effect of batroxobin combine with ginkgo-damole injection on hemodynamics, coagulation function, fibrinolytic function and related factors in patients with sudden deafness

    Directory of Open Access Journals (Sweden)

    Xiang Xu

    2017-11-01

    Full Text Available Objective: To study the effects of combined use of Batroxobin and Ginkgo Leaf Extract and Dipyridamole Injection on hemodynamics, coagulation function, fibrinolytic function and related factors in patients with sudden deafness. Methods: A total of 94 patients with sudden deafness in our hospital were selected, and divided them into control group and observation group randomly, 47 cases in each group. All patients were given 10BU batroxobin injection intravenous drip after admission every other day; And the patients of observation group were given intravenous drip of 30ml ginkgo-damole injection, 1 time a day. The hemodynamics, coagulation function, fibrinolytic function and related factors were detected and compared between the two groups before and after treatment. Results: Before treatment, there was no statistical difference in hemodynamics, coagulation function, fibrinolytic function and related factors between the two groups; After treatment, the levels of WBV and PV in the control group was (5.21±0.58 mPa/s and (1.78±0.32 mPa/s, and the observation group was (4.13±0.47 mPa/s and (1.31±0.26 mPa/s, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups; The levels of PT, APTT, TT and PF was (19.22±3.98 s, (43.57±9.88 s, (15.64±3.27 s and (58.22±10.58 μg/L, and the observation group was (23.97±4.82 s, (52.49±10.38 s, (20.59±4.15 s and (41.03±8.46 μg/L, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups; The levels of Fib, D-dimer and FDP was (4.52±0.93 g/L, (6.53±1.88 mg/L and (8.17±2.34 μg/mL, and the observation group was (3.13±0.75 g/L, (9.75±2.14 mg/L, (13.52±2.58 μg/ mL, compared with the same group before treatment, there were statistical difference, and there was also statistical difference between the two groups; The serum

  20. Microvascular obstruction after successful fibrinolytic therapy in acute myocardial infarction. Comparison of reteplase vs reteplase+abciximab: A cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Tiziano Gherli

    2010-05-01

    Full Text Available Background. About one third of patients with TIMI 3 after reperfusion have evidence of microvascular obstruction (MO which represents an independent predictor of myocardial wall rupture. This explains all efforts made to prevent MO. Magnetic resonance imaging (MRI has proved to be particularly useful in detecting MO. The aim of this study was to evaluate with MRI if different fibrinolytic regimens in acute myocardial infarction display different effects on left ventricle (LV volumes and ejection fraction (EF, as well as on myocardial infarct size (MIsz and MO. Methods. Twenty male patients, mean age 58 years, affected by acute myocardial infarction, ten anterior and ten inferior, were treated with: full dose reteplase in ten, and half dose reteplase plus full dose abciximab (R+Abcx in the other ten patients. In the fourth day after hospital admission, MRI STIR T2 images were used to quantify MIsz, while 2dflash cineloops were used after the injection of gadolinium, to quantify LV volumes, EF and to detect MO. Results. LV EF was higher in R+Abcx 51±10 than in reteplase 41±8. MIsz was similar in both treatment groups: however a close relationship was present between MIsz and EF in the reteplase group indicating that the greater the MIsz the lower the EF. In R+Abcx this relationship was no longer present, suggesting a protective effect of the drug on microcirculation. In fact extensive MO was present in 25% of all cases, 80% of which in the reteplase group while only 20% in R+Abcx. Conclusion. R+Abcx prevents MO: compared to traditional fibrinolytic therapy it allows better LV function and most likely improved long term survival.

  1. Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

    Science.gov (United States)

    Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

  2. Highly active antiretroviral therapy normalizes the function of progenitor cells in human immunodeficiency virus-infected patients

    DEFF Research Database (Denmark)

    Dam Nielsen, S.; Ersbøll, A. K.; Mathiesen, L.

    1998-01-01

    -infected patients were determined prior to HAART and after 2, 4, 8, and 12 weeks of therapy. The mean number of colony-forming units (cells) per milliliter (cfu/mL) was 15.0 prior to HAART vs. 109.8 in healthy controls (P.../mL eliminated the differences between HIV-infected patients and controls. Significant increases in numbers of CD34 cells were not detected. Of importance, the cloning efficiency of CD34 cells increased from 1.7% prior to therapy to a peak at 18.7% (P=.003). In conclusion, HAART normalized CD34 cell function...

  3. Malware Normalization

    OpenAIRE

    Christodorescu, Mihai; Kinder, Johannes; Jha, Somesh; Katzenbeisser, Stefan; Veith, Helmut

    2005-01-01

    Malware is code designed for a malicious purpose, such as obtaining root privilege on a host. A malware detector identifies malware and thus prevents it from adversely affecting a host. In order to evade detection by malware detectors, malware writers use various obfuscation techniques to transform their malware. There is strong evidence that commercial malware detectors are susceptible to these evasion tactics. In this paper, we describe the design and implementation of a malware normalizer ...

  4. The research on biodistribution of 131I-iodosennoside A in normal mice and to evaluate myocardial activity

    International Nuclear Information System (INIS)

    Wang Junhu; Yin Zhiqi; Jiang Cuihua; Jiang Xiao; Li Yue; Zhang Jian; Sun Ziping; Ni Yicheng

    2013-01-01

    Purpose: The objective of this project is to evaluate biodistribution of [ 131 I]-Iodosennoside A in normal mice and explore the feasibility on the diagnosis of myocardial infarction. Methods: Iodogen method was used to radioiodinate sennoside A with 131 I. [ 131 I] Iodosennoside A was intravenously injected into mice. Three groups of mice were killed at 4 h, 24 h and 48 h post injection respectively and the radioactive uptake in major organs were calculated. Rats were subjected to left anterior descending (LAD) coronary artery ligation to induce acute myocardial infarction. Rat models of myocardial infarction were intravenously injected [ 131 I] iodosennoside A. 24 h after injection of [ 131 I] iodosennoside A, the regional distribution of radioiodinated sennoside A was determined by radioactivity counting technique. 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining and autoradiography were per- formed with 2 mm thick sections of hearts for postmortem verifications. Results: The study showed high uptake of [ 131 I] iodosennoside A in kidneys and fast blood clearance. At 24 h post injection, radioactivity concentration in infarcted myocardium was over 11.9 times higher than in normal myocardium. Preferential uptake of the [ 131 I] iodosennoside A in necrotic tissue was confirmed by perfect match of images from TTC staining and autoradiography. Conclusion: The result proved that [ 131 I] iodosennoside A has myocardial necrosis affinity and may serve as a marker on the diagnosis of myocardial infarction. (authors)

  5. NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: impact of renin-angiotensin system activity

    DEFF Research Database (Denmark)

    Due-Andersen, R; Pedersen-Bjergaard, U; Høi-Hansen, T

    2008-01-01

    subjects with high-RAS activity and 10 subjects with low-RAS activity (age 26 +/- 1 yr; mean +/- SE) were studied in a single-blinded, randomized, counterbalanced, crossover study on three occasions separated by at least 3 wk: 1) hypoglycemia (mean nadir plasma glucose 2.7 +/- 0.5 mmol/l), 2) hypoxemia...

  6. The Anticomplementary Activity of ’Fusobacterium polymorphum’ in Normal and C-4 Deficient Sources of Guinea Pig Complement.

    Science.gov (United States)

    1977-01-12

    A complement consumption assay was used to show that the anticomplementary activity of a cell wall preparation from F. polymorphum in guinea pig complement...tests with C𔃾-deficient guinea pig sera confirmed that F. polymorphum cell walls were capable of generating alternate complement pathway activity in guinea pig sera.

  7. Rocks: A Concrete Activity That Introduces Normal Distribution, Sampling Error, Central Limit Theorem and True Score Theory

    Science.gov (United States)

    Van Duzer, Eric

    2011-01-01

    This report introduces a short, hands-on activity that addresses a key challenge in teaching quantitative methods to students who lack confidence or experience with statistical analysis. Used near the beginning of the course, this activity helps students develop an intuitive insight regarding a number of abstract concepts which are key to…

  8. Fibrinogen Vicenza and Genova II: two new cases of congenital dysfibrinogenemia with isolated defect of fibrin monomer polymerization and inhibitory activity on normal coagulation.

    Science.gov (United States)

    Rodeghiero, F; Castaman, G C; Dal Belin Peruffo, A; Dini, E; Galletti, A; Barone, E; Gastaldi, G

    1987-06-03

    Two new cases of congenital dysfibrinogenemia are presented in which defective fibrin monomer polymerization and inhibitory activity on normal coagulation were observed. They have been tentatively called fibrinogen Vicenza and Genova II. The first was discovered in a family with mild bleeding diathesis, the second in an asymptomatic family. In almost all reported cases of fibrinogens with defective fibrin monomer polymerization, additional functional or structural defects have been detected. In our cases, on the contrary, detailed investigations failed to show any other abnormality. Fibrinogen Genova II is apparently identical to fibrinogen Baltimore IV, whereas fibrinogen Vicenza is similar to fibrinogen Troyes and Genova I, but also exerts an evident inhibitory activity on normal coagulation and differs from fibrinogen Genova II and Baltimore IV showing a different kinetic pattern of fibrin monomer polymerization.

  9. Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake.

    Science.gov (United States)

    Hogenkamp, P S; Zhou, W; Dahlberg, L S; Stark, J; Larsen, A L; Olivo, G; Wiemerslage, L; Larsson, E-M; Sundbom, M; Benedict, C; Schiöth, H B

    2016-11-01

    In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m - 2 ) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m - 2 ), both before and 30 min after consumption of a standardized meal (~260 kcal). Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (Pfood intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (Pfood intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.

  10. Effects of the Healthy Start randomized intervention trial on physical activity among normal weight preschool children predisposed to overweight and obesity.

    Directory of Open Access Journals (Sweden)

    Mina Nicole Händel

    Full Text Available There is limited evidence to support the effectiveness of primary interventions aiming to prevent excess weight gain among young children. Evaluating behavioral changes, such as physical activity (PA, may add to future development of efficient interventions. The objective was to evaluate the effect on PA outcomes of the 15 month Healthy Start intervention that focused on changing diet, PA, sleep and stress management among normal weight but obesity-prone preschool children. Children were defined as obesity-prone if they had a birth weight > 4,000 g, mothers with a pre-pregnancy body mass index of > 28 kg/m2, or mothers with ≤ 10 years of schooling.From a baseline study population of 635 normal weight 2-6 year old preschool children from the greater Copenhagen area, parents of 307 children had given information on PA at both the baseline and follow-up examinations. PA was obtained from a 7 days recording in the Children's Physical Activity Questionnaire. Time used for sport activities were combined with outdoor playing time to achieve a proxy of total PA level of moderate to vigorous intensity.Linear regression analyses revealed that at follow-up the intervention group spent more time on sports and outdoor activities combined per week than the control group (ITT analyses: intervention: 400 min/week; 95% confidence interval (CI: 341, 459 versus control: 321 min/week; 95% CI: 277, 366; p = 0.02, although no significant intervention effects were seen for each of the subcategories, e.g. sports participation, outdoor activities, screen time, or commuting frequency.Our results suggest that the overall time spent on sports and outdoor activities combined was increased at follow-up among normal weight obesity-prone children, as a result of the Healthy Start intervention.ClinicalTrials.gov NCT01583335.

  11. Effects of the Healthy Start randomized intervention trial on physical activity among normal weight preschool children predisposed to overweight and obesity.

    Science.gov (United States)

    Händel, Mina Nicole; Larsen, Sofus Christian; Rohde, Jeanett Friis; Stougaard, Maria; Olsen, Nanna Julie; Heitmann, Berit Lilienthal

    2017-01-01

    There is limited evidence to support the effectiveness of primary interventions aiming to prevent excess weight gain among young children. Evaluating behavioral changes, such as physical activity (PA), may add to future development of efficient interventions. The objective was to evaluate the effect on PA outcomes of the 15 month Healthy Start intervention that focused on changing diet, PA, sleep and stress management among normal weight but obesity-prone preschool children. Children were defined as obesity-prone if they had a birth weight > 4,000 g, mothers with a pre-pregnancy body mass index of > 28 kg/m2, or mothers with ≤ 10 years of schooling. From a baseline study population of 635 normal weight 2-6 year old preschool children from the greater Copenhagen area, parents of 307 children had given information on PA at both the baseline and follow-up examinations. PA was obtained from a 7 days recording in the Children's Physical Activity Questionnaire. Time used for sport activities were combined with outdoor playing time to achieve a proxy of total PA level of moderate to vigorous intensity. Linear regression analyses revealed that at follow-up the intervention group spent more time on sports and outdoor activities combined per week than the control group (ITT analyses: intervention: 400 min/week; 95% confidence interval (CI): 341, 459 versus control: 321 min/week; 95% CI: 277, 366; p = 0.02), although no significant intervention effects were seen for each of the subcategories, e.g. sports participation, outdoor activities, screen time, or commuting frequency. Our results suggest that the overall time spent on sports and outdoor activities combined was increased at follow-up among normal weight obesity-prone children, as a result of the Healthy Start intervention. ClinicalTrials.gov NCT01583335.

  12. Activities of the nuclear emergency assistance and training center. Strengthening co-operation with parties in normal circumstances

    International Nuclear Information System (INIS)

    Watanabe, Fumitaka; Matsui, Tomoaki; Nomura, Tamotsu

    2005-01-01

    The Japan Nuclear Cycle Development Institute (JNC) and the Japan Atomic Energy Research Institute (JAERI) established the Nuclear Emergency Assistance and Training Center (NEAT) in March 2002. The center aims to provide various support nuclear safety regulatory bodies, local governments and nuclear facility licenses as specialists about nuclear and radiological issues according to the role shown in the Basic Disaster Management Plan. Upon a nuclear and/or radiological disaster occurring in Japan, NEAT will send specialists to the disaster scene, and offer the use of special equipments. NEAT maintains frequent contact with related organizations in normal circumstance. NEAT also participates in nuclear emergency exercises instructed by the parties concerned, which has contributed to the brewing of mutual trust with related organizations. In October 2005, JNC and JAERI merged into a new organization named the Japan Atomic Energy Agency (JAEA). NEAT, as a section of the organization, continuously deals with nuclear emergencies. (author)

  13. mPeriod2 Brdm1 and other single Period mutant mice have normal food anticipatory activity.

    Science.gov (United States)

    Pendergast, Julie S; Wendroth, Robert H; Stenner, Rio C; Keil, Charles D; Yamazaki, Shin

    2017-11-14

    Animals anticipate the timing of food availability via the food-entrainable oscillator (FEO). The anatomical location and timekeeping mechanism of the FEO are unknown. Several studies showed the circadian gene, Period 2, is critical for FEO timekeeping. However, other studies concluded that canonical circadian genes are not essential for FEO timekeeping. In this study, we re-examined the effects of the Per2 Brdm1 mutation on food entrainment using methods that have revealed robust food anticipatory activity in other mutant lines. We examined food anticipatory activity, which is the output of the FEO, in single Period mutant mice. Single Per1, Per2, and Per3 mutant mice had robust food anticipatory activity during restricted feeding. In addition, we found that two different lines of Per2 mutant mice (ldc and Brdm1) anticipated restricted food availability. To determine if FEO timekeeping persisted in the absence of the food cue, we assessed activity during fasting. Food anticipatory (wheel-running) activity in all Period mutant mice was also robust during food deprivation. Together, our studies demonstrate that the Period genes are not necessary for the expression of food anticipatory activity.

  14. Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake

    OpenAIRE

    Hogenkamp, P S; Zhou, W; Dahlberg, L S; Stark, J; Larsen, A L; Olivo, G; Wiemerslage, L; Larsson, E-M; Sundbom, M; Benedict, C; Schi?th, H B

    2016-01-01

    BACKGROUND: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. OBJECTIVE: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese...

  15. Antitoxin activity of Mimosa pudica root extracts against Naja naja and Bangarus caerulus venoms

    Directory of Open Access Journals (Sweden)

    Subramani Meenatchisundaram

    2009-06-01

    Full Text Available Aqueous extract of dried roots of Mimosa pudica was tested for inhibitory activity on lethality, phospholipase activity, edema forming activity, fibrinolytic activity and hemorrhagic activity of Naja naja and Bangarus caerulus venoms. The aqueous extract displayed a significant inhibitory effect on the lethality, phospholipase activity, edema forming activity, fibrinolytic activity and hemorrhagic activity. About 0.14 mg and 0.16 mg of M. pudica extracts were able to completely neutralize the lethal activity of 2LD50 of Naja naja and Bangarus caerulus venoms respectively. The present finding suggests that aqueous extract of M. pudica root possesses compounds, which inhibit the activity of Naja naja and Bangarus caerulus venoms.

  16. Antitoxin activity of Mimosa pudica root extracts against Naja naja and Bangarus caerulus venoms

    Directory of Open Access Journals (Sweden)

    Subramani Meenatchisundaram, Selvin Priyagrace, Ramasamy Vijayaraghavan, Ambikapathi Velmurugan, Govindarajan Parameswari, Antonysamy Michael

    2009-12-01

    Full Text Available Aqueous extract of dried roots of Mimosa pudica was tested for inhibitory activity on lethality, phospholipase activity, edema forming activity, fibrinolytic activity and hemorrhagic activity of Naja naja and Bangarus caerulus venoms. The aqueous extract displayed a significant inhibitory effect on the lethality, phospholipase activity, edema forming activity, fibrinolytic activity and hemorrhagic activity. About 0.14 mg and 0.16 mg of M. pudica extracts were able to completely neutralize the lethal activity of 2LD50 of Naja naja and Bangarus caerulus venoms respectively. The present finding suggests that aqueous extract of M. pudica root possesses compounds, which inhibit the activity of Naja naja and Bangarus caerulus venoms.

  17. Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS.

    Science.gov (United States)

    An, Jing; Hu, Fangdi; Wang, Changhong; Zhang, Zijia; Yang, Li; Wang, Zhengtao

    2016-09-01

    1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

  18. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain of function mutations

    DEFF Research Database (Denmark)

    Galan-Diez, Marta; Isa, Adiba; Ponzetti, Marco

    2016-01-01

    of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5...... mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation...... of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM...

  19. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain-of-function mutations.

    Science.gov (United States)

    Galán-Díez, Marta; Isa, Adiba; Ponzetti, Marco; Nielsen, Morten Frost; Kassem, Moustapha; Kousteni, Stavroula

    2016-03-01

    Osteoblasts are emerging regulators of myeloid malignancies since genetic alterations in them, such as constitutive activation of β-catenin, instigate their appearance. The LDL receptor-related protein 5 (LRP5), initially proposed to be a co-receptor for Wnt proteins, in fact favors bone formation by suppressing gut-serotonin synthesis. This function of Lrp5 occurring in the gut is independent of β-catenin activation in osteoblasts. However, it is unknown whether Lrp5 can act directly in osteoblast to influence other functions that require β-catenin signaling, particularly, the deregulation of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5 mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM patients showed normal hematopoiesis, normal percentage of myeloid cells, and lack of anemia. We conclude that Lrp5 GOF mutations do not activate β-catenin signaling in osteoblasts. As a result, myeloid lineage differentiation is normal in HBM patients and mice. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. Published

  20. Oestrous behaviour and ovarian activity in D'man and Sardi breeds of Moroccan sheep under normal and experimental photoperiods

    International Nuclear Information System (INIS)

    Lahlou-Kassi, A.; Boukhliq, R.

    1988-01-01

    The effect of photoperiod on sexual activity was investigated in Sardi and D'man ewes. Twenty ewes from each breed were subjected to an experimental photoperiod corresponding to latitude 56 deg. N. Control ewes (12 per breed) were maintained under natural photoperiod (32 deg. N). Behavioural oestrus and ovarian activity were monitored using penis deviated rams and plasma progesterone levels. Preliminary results from this study show that an increase in amplitude of photoperiod variations causes a decrease in the expression of oestrous behaviour in D'man ewes during the period of decreasing daylight. Ovarian activity remained unchanged. Sardi ewes were not markedly affected by change in photoperiod. (author). 13 refs, 3 figs, 1 tab

  1. Making nuclear 'normal'

    International Nuclear Information System (INIS)

    Haehlen, Peter; Elmiger, Bruno

    2000-01-01

    The mechanics of the Swiss NPPs' 'come and see' programme 1995-1999 were illustrated in our contributions to all PIME workshops since 1996. Now, after four annual 'waves', all the country has been covered by the NPPs' invitation to dialogue. This makes PIME 2000 the right time to shed some light on one particular objective of this initiative: making nuclear 'normal'. The principal aim of the 'come and see' programme, namely to give the Swiss NPPs 'a voice of their own' by the end of the nuclear moratorium 1990-2000, has clearly been attained and was commented on during earlier PIMEs. It is, however, equally important that Swiss nuclear energy not only made progress in terms of public 'presence', but also in terms of being perceived as a normal part of industry, as a normal branch of the economy. The message that Swiss nuclear energy is nothing but a normal business involving normal people, was stressed by several components of the multi-prong campaign: - The speakers in the TV ads were real - 'normal' - visitors' guides and not actors; - The testimonials in the print ads were all real NPP visitors - 'normal' people - and not models; - The mailings inviting a very large number of associations to 'come and see' activated a typical channel of 'normal' Swiss social life; - Spending money on ads (a new activity for Swiss NPPs) appears to have resulted in being perceived by the media as a normal branch of the economy. Today we feel that the 'normality' message has well been received by the media. In the controversy dealing with antinuclear arguments brought forward by environmental organisations journalists nowadays as a rule give nuclear energy a voice - a normal right to be heard. As in a 'normal' controversy, the media again actively ask themselves questions about specific antinuclear claims, much more than before 1990 when the moratorium started. The result is that in many cases such arguments are discarded by journalists, because they are, e.g., found to be

  2. Equilibrium sampling of environmental pollutants in fish: comparison with lipid-normalized concentrations and homogenization effects on chemical activity.

    Science.gov (United States)

    Jahnke, Annika; Mayer, Philipp; Adolfsson-Erici, Margaretha; McLachlan, Michael S

    2011-07-01

    Equilibrium sampling of organic pollutants into the silicone polydimethylsiloxane (PDMS) has recently been applied in biological tissues including fish. Pollutant concentrations in PDMS can then be multiplied with lipid/PDMS distribution coefficients (D(Lipid,PDMS) ) to obtain concentrations in fish lipids. In the present study, PDMS thin films were used for equilibrium sampling of polychlorinated biphenyls (PCBs) in intact tissue of two eels and one salmon. A classical exhaustive extraction technique to determine lipid-normalized PCB concentrations, which assigns the body burden of the chemical to the lipid fraction of the fish, was additionally applied. Lipid-based PCB concentrations obtained by equilibrium sampling were 85 to 106% (Norwegian Atlantic salmon), 108 to 128% (Baltic Sea eel), and 51 to 83% (Finnish lake eel) of those determined using total extraction. This supports the validity of the equilibrium sampling technique, while at the same time confirming that the fugacity capacity of these lipid-rich tissues for PCBs was dominated by the lipid fraction. Equilibrium sampling was also applied to homogenates of the same fish tissues. The PCB concentrations in the PDMS were 1.2 to 2.0 times higher in the homogenates (statistically significant in 18 of 21 cases, p equilibrium sampling and partition coefficients determined using tissue homogenates. Copyright © 2011 SETAC.

  3. Low plasma aldosterone despite normal plasma renin activity in uncomplicated type 1 diabetes mellitus : effects of RAAS stimulation

    NARCIS (Netherlands)

    Luik, PT; Kerstens, MN; Hoogenberg, K; Navis, GJ; Dullaart, RPF

    Background Data on levels and responsiveness of PRA and aldosterone in type 1 diabetes mellitus are conflicting. Earlier studies were not standardized with respect to the type of diabetes mellitus, the presence of diabetic complications or sodium intake. Therefore, we studied plasma renin activity

  4. Bile acid sequestration normalizes plasma cholesterol and reduces atherosclerosis in hypercholesterolemic mice. No additional effect of physical activity

    NARCIS (Netherlands)

    Meissner, Maxi; Wolters, Henk; de Boer, Rudolf A.; Havinga, Rick; Boverhof, Renze; Bloks, Vincent W.; Kuipers, Folkert; Groen, Albert K.

    Aims: Bile acid sequestrants (BAS) and physical activity (RUN) decrease incidence of cardiovascular events. Both treatments are often prescribed, yet it is not known whether their beneficial effects are additive. We assessed the effects of BAS treatment alone and in combination with RUN on

  5. Inhibition of muscle glycogen synthase activity and non-oxidative glucose disposal during hypoglycaemia in normal man

    DEFF Research Database (Denmark)

    Ørskov, Lotte; Bak, Jens Friis; Abildgaard, Ulrik

    1996-01-01

    The purpose of the present study was to evaluate the role of muscle glycogen synthase activity in the reduction of glucose uptake during hypoglycaemia. Six healthy young men were examined twice; during 120 min of hyperinsulinaemic (1.5 mU.kg-1. min-1) euglycaemia followed by: 1)240 min of graded ...

  6. Radiorestoring activity of few nucleotides on normal tissues of Jerusalem Artichoke after an irradiation with γ rays of 60Co

    International Nuclear Information System (INIS)

    Jonard, Robert; Bayonove, Jacqueline; Riedel, Michel.

    1978-01-01

    The nucleotides tested: adenosine triphosphate (ATP) and cyclic adenosine 3',5'-monophosphate (3',5'-cAMP), guanosine triphosphate (GTP) and cyclic guanosine 3',5'-monophosphate (3',5'-cGMP), are able to restore proliferation to irradiated (γ irradiation, 3,000 rad) Jesusalem Artichoke tissue. The 3',5'-cGMP shows the greater radiorestoring activity [fr

  7. Forehead Skin Blood Flow in Normal Neonates during Active and Quiet Sleep, Measured with a Diode Laser Doppler Instrument

    NARCIS (Netherlands)

    Suichies, H.E.; Aarnoudse, J.G.; Okken, A.; Jentink, H.W.; de Mul, F.F.M.; Greve, Jan

    1988-01-01

    Changes in forehead skin blood flow during active and quiet sleep were determined in 16 healthy neonates using a recently developed semi-conductor laser Doppler flow meter without light conducting fibres. Measurements were carried out at a postnatal age varying from 5 hours to 7 days. The two sleep

  8. Salivary lipase and a-amylase activities are higher in overweight than in normal weight subjects: Influences on dietary beharior

    NARCIS (Netherlands)

    Mennella, I.; Fogliano, V.; Vitaglione, P.

    2014-01-01

    Mounting evidence shows that hedonic eating, leading to overeating just for pleasure, can be driven by oro-sensory factors through the activation of reward processing and learning in the brain. Foods rich in sugars and fats are potent rewards and saliva composition influences oral taste, texture and

  9. Sorting Nexin 2 (SNX2): a potential marker of active thyrocytes in normal and hyperfunctioning thyroid disorders.

    Science.gov (United States)

    Kanzawa, Maki; Hara, Shigeo; Semba, Shuho; Yokozaki, Hiroshi; Hirokawa, Mitsuyoshi; Itoh, Tomoo

    2014-04-01

    Sorting nexins (SNXs) are a large, diverse group of cytoplasmic and membrane-associated proteins that function in a variety of cellular processes, including endocytosis, protein trafficking, and the retrieval of transmembrane proteins. In this study, we demonstrated that SNX2 is expressed in columnar and active thyroid follicular cells but not in flattened inactive thyrocytes. Morphometric analysis revealed a significant correlation between SNX2 positivity and columnar cell morphology. Immunohistochemical staining of serial sections of the thyroid tissue indicated that SNX2 localization was similar to sortilin, a protein expressed by active thyrocytes. Expression of SNX2 in thyrocytes is particularly marked and extensive in most hyperstimulated thyroid disorders, including Graves disease (diffusely SNX2 positive in 73.3% patients) and functioning nodules (93.8% patients). SNX2 immunolocalization in hyperstimulated follicular epithelial cells was specific among the SNXs family members examined. These results support the utility of SNX2 as a novel marker of active thyrocytes and reflect the endosomal trafficking activity in these cells.

  10. Reconstructing Normality

    DEFF Research Database (Denmark)

    Gildberg, Frederik Alkier; Bradley, Stephen K.; Fristed, Peter Billeskov

    2012-01-01

    Forensic psychiatry is an area of priority for the Danish Government. As the field expands, this calls for increased knowledge about mental health nursing practice, as this is part of the forensic psychiatry treatment offered. However, only sparse research exists in this area. The aim of this study...... was to investigate the characteristics of forensic mental health nursing staff interaction with forensic mental health inpatients and to explore how staff give meaning to these interactions. The project included 32 forensic mental health staff members, with over 307 hours of participant observations, 48 informal....... The intention is to establish a trusting relationship to form behaviour and perceptual-corrective care, which is characterized by staff's endeavours to change, halt, or support the patient's behaviour or perception in relation to staff's perception of normality. The intention is to support and teach the patient...

  11. Comparison of {gamma}-ray profile across active normal and reverse faults; Seidansogata to gyakudansogata katsudanso ni okeru hoshano tansa kekka no hikaku

    Energy Technology Data Exchange (ETDEWEB)

    Iwata, A; Wada, N; Sumi, H [Shimada Technical Consultants, Ltd., Shimane (Japan); Yamauchi, S; Iga, T [Shimane Univ., Shimane (Japan)

    1996-10-01

    Active faults confirmed at trench and outcrop were surveyed by the {gamma}-ray spectrometry. The active fault found at trench is a normal fault, and that found at outcrop is a reverse fault. The {gamma}-ray spectral characteristics of these two types of faults were compared to each other. The normal fault is named as Asagane fault located in Aimi-machi, Saihaku-gun, Tottori prefecture. The reverse fault is named as Yokota reverse fault located in Yokota-cho, Nita-gun, Shimane prefecture. Rises of radon gas indicating the existence of opening cracks were confirmed above the fault for the normal fault, and at the side of thrust block for the reverse fault. It was considered that such characteristics were caused by the difference of fault formation in the tensile stress field and in the compressive stress field. It was also reconfirmed that much more information as to faults can be obtained by the combined exploration method using the total counting method and the spectral method. 14 refs., 7 figs.

  12. Normalizing the maximum permissible seal failure of the fuel cladding of VVER and the activity of the fission products in the coolant

    International Nuclear Information System (INIS)

    Luzanova, L.M.; Miglo, V.N.; Slavyagin, P.D.

    1993-01-01

    In most countries developing a nuclear power industry based on pressurized water reactors, one of the conditions for issuing a license under normal operating conditions for issuing a license stipulates that the fuel elements may not lose their hermetic seal either under normal operating conditions or during presumable disturbances of the conditions of normal use. At a conference on radiation safety the ALARA principle was taken to be fundamental, it being attempted to keep the activity of the coolant of the primary circuit, including the fission products emerging from unsealed fuel elements, to a level as low as reasonably possible. As many years of experience in the nuclear power industry have shown, nuclear power stations are in many cases operated with nonhermetic fuel elements in the core. Therefore, from the point of view of safety and economy, the best way to operate a power plant is to try to ensure maximum burnup of the fuel of the unsealed elements as they operate within the limits of safe activity of the fission products in the fuel circuits

  13. Moringa oleifera Lam.: Protease activity against blood coagulation cascade.

    Science.gov (United States)

    Satish, A; Sairam, Sudha; Ahmed, Faiyaz; Urooj, Asna

    2012-01-01

    The present study evaluated the protease activity of aqueous extracts of Moringa oleifera (Moringaceae) leaf (MOL) and root (MOR). Protease activity was assayed using casein, human plasma clot and human fibrinogen as substrates. Caseinolytic activity of MOL was significantly higher (P ≤ 0.05) than that of MOR. Similar observations were found in case of human plasma clot hydrolyzing activity, wherein MOL caused significantly higher (P ≤ 0.05) plasma clot hydrolysis than MOR. Zymographic techniques were used to detect proteolytic enzymes following electrophoretic separation in gels. Further, both the extracts exhibited significant procoagulant activity as reflected by a significant decrease (P ≤ 0.05) in recalcification time, accompanied by fibrinogenolytic and fibrinolytic activities; clotting time was decreased from 180 ± 10 sec to 119 ± 8 sec and 143 ± 10 sec by MOL and MOR, respectively, at a concentration of 2.5 mg/mL. Fibrinogenolytic (human fibrinogen) and fibrinolytic activity (human plasma clot) was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), plate method and colorimetric method. Zymographic profile indicated that both the extracts exerted their procoagulant activity by selectively hydrolyzing Aα and Bβ subunits of fibrinogen to form fibrin clot, thereby exhibiting fibrinogenolytic activity. However, prolonged incubation resulted in degradation of the formed fibrin clot, suggesting fibrinolytic like activity. These findings support the traditional usage of M. oleifera extracts for wound healing.

  14. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    Science.gov (United States)

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models.

  15. Expression and Localization of Peroxisome Proliferator-Activated Receptors and Nuclear Factor κB in Normal and Lesional Psoriatic Skin

    DEFF Research Database (Denmark)

    Westergaard, Majken; Henningsen, Jeanette; Johansen, Claus

    2003-01-01

    Abnormal epidermal proliferation and differentiation characterize the inflammatory skin disease psoriasis. Here we demonstrate that expression of PPARdelta mRNA and protein is markedly upregulated in psoriatic lesions and that lipoxygenase products accumulating in psoriatic lesions are potent...... activators of PPARdelta. The expression levels of NF-kappaB p50 and p65 were not significantly altered in lesional compared with nonlesional psoriatic skin. In the basal layer of normal epidermis both p50 and p65 were sequestered in the cytoplasm, whereas p50, but not p65, localized to nuclei...... in the suprabasal layers, and this distribution was maintained in lesional psoriatic skin. In normal human keratinocytes PPAR agonists neither impaired IL-1beta-induced translocation of p65 nor IL-1beta-induced NF-kappaB DNA binding. We show that PPARdelta physically interacts with the N-terminal Rel homology...

  16. Angiotensin-converting enzyme-inhibitory activity in protein hydrolysates from normal and anthracnose disease-damaged Phaseolus vulgaris seeds.

    Science.gov (United States)

    Hernández-Álvarez, Alan Javier; Carrasco-Castilla, Janet; Dávila-Ortiz, Gloria; Alaiz, Manuel; Girón-Calle, Julio; Vioque-Peña, Javier; Jacinto-Hernández, Carmen; Jiménez-Martínez, Cristian

    2013-03-15

    Bean seeds are an inexpensive source of protein. Anthracnose disease caused by the fungus Colletotrichum lindemuthianum results in serious losses in common bean (Phaseolus vulgaris L.) crops worldwide, affecting any above-ground plant part, and protein dysfunction, inducing the synthesis of proteins that allow plants to improve their stress tolerance. The aim of this study was to evaluate the use of beans damaged by anthracnose disease as a source of peptides with angiotensin-converting enzyme (ACE-I)-inhibitory activity. Protein concentrates from beans spoiled by anthracnose disease and from regular beans as controls were prepared by alkaline extraction and precipitation at isolelectric pH and hydrolysed using Alcalase 2.4 L. The hydrolysates from spoiled beans had ACE-I-inhibitory activity (IC(50) 0.0191 mg protein mL(-1)) and were very similar to those from control beans in terms of ACE-I inhibition, peptide electrophoretic profile and kinetics of hydrolysis. Thus preparation of hydrolysates using beans affected by anthracnose disease would allow for revalorisation of this otherwise wasted product. The present results suggest the use of spoiled bean seeds, e.g. anthracnose-damaged beans, as an alternative for the isolation of ACE-I-inhibitory peptides to be further introduced as active ingredients in functional foods. © 2012 Society of Chemical Industry.

  17. A Comparative Study of Personality Traits and Brain Behavioral activation Systems and Inhibition in Women with Cancer, Cardiovascular Diseases and Normal Women

    Directory of Open Access Journals (Sweden)

    Sohrab Amiri

    2017-04-01

    Full Text Available Background and Objectives: Chronic diseases are among the most important causes of mortality. The aim of the current study was to compare the Brain/behavioral systems and Dark personality traits of Machiavellianism, narcissism, and psychopathy in cancer, cardiovascular female patients and normal women. Methods: In this study, 60 individuals were selected using available sampling in three groups of 20 cancer patients, cardiovascular patients, and normal subjects. Finally, in order to test the goals and hypotheses of the research, the participants were studied based on Behavioral Activation System and Behavioral Inhibition System, and Dark Triad traits. Data analysis was performed using multivariate ANOVA, univariate ANOVA and post-hoc tests. Results: In this study, there was a significant difference among the three groups in Brain/behavioral systems and traits of Machiavellianism, narcissism, and psychopathy, so that the cancer and cardiovascular patients had higher score in dark triad traits compared to normal individuals. Also, the cancer patients had a higher score in Machiavellianism trait compared to the cardiovascular patients. In the brain/behavioral systems, cardiovascular and cancer patients had higher score in behavioral inhibition system (BIS component compared to the normal individuals in the of behavioral inhibition system (BIS. Also, in the reward seeking subscale of behavioral activation system (BAS-f, cancer patients had a higher score compared to cardiovascular patients, which was significantly different. Conclusion: The results of this study indicated that cancer and cardiovascular patients, have greater extent of social disgusting personality traits as well as behavioral inhibition system as anxiety-predisposing factor.

  18. Differential immunotoxic effects of ethanol on murine EL-4 lymphoma and normal lymphocytes is mediated through increased ROS production and activation of p38MAPK.

    Science.gov (United States)

    Premachandran, Sudha; Khan, Nazir M; Thakur, Vikas S; Shukla, Jyoti; Poduval, T B

    2012-08-01

    Ethanol has been used to achieve thymic depletion in myasthenia gravis patients. Ethanol (95%) has also been used widely in the therapy of many tumors including hepatocellular carcinoma. In light of these findings, we delineated the differential immunotoxic behavior and mechanism of lower concentration of ethanol towards murine EL-4 lymphoma and its normal counterpart lymphocytes. EL-4 lymphoma and normal lymphocytes were cultured with ethanol (0%-5%) for 6 h and cytotoxicity was measured by various methods. EL-4 cells treated with ethanol showed concentration-dependent loss of viability at 2%-5% ethanol concentration and exhibit proliferative arrest at preG1 stage. Acridine-orange and ethidium-bromide staining indicated that ethanol induced death in EL-4 cells, by induction of both apoptosis and necrosis which was further supported by findings of DNA-fragmentation and trypan blue dye exclusion test. However, treatment of lymphocytes with similar concentration of ethanol did not show any death-associated parameters. Furthermore, ethanol induced significantly higher ROS generation in EL-4 cells as compared to lymphocytes and caused PARP cleavage and activation of apoptotic proteins like p53 and Bax, in EL-4 cells and not in normal lymphocytes. In addition, ethanol exposure to EL-4 cells led to phosphorylation of p38MAPK, and upregulation of death receptor Fas (CD95). Taken together, these results suggest that ethanol upto a concentration of 5% caused no significant immunotoxicity towards normal lymphocytes and induced cell death in EL-4 cells via phosphorylation of p38MAPK and regulation of p53 leading to further activation of both extrinsic (Fas) and intrinsic (Bax) apoptotic markers.

  19. Effects of the Healthy Start randomized intervention trial on physical activity among normal weight preschool children predisposed to overweight and obesity

    DEFF Research Database (Denmark)

    Händel, Mina Nicole; Larsen, Sofus Christian; Rohde, Jeanett Friis

    2017-01-01

    was to evaluate the effect on PA outcomes of the 15 month Healthy Start intervention that focused on changing diet, PA, sleep and stress management among normal weight but obesity-prone preschool children. Children were defined as obesity-prone if they had a birth weight > 4,000 g, mothers with a pre...... was obtained from a 7 days recording in the Children’s Physical Activity Questionnaire. Time used for sport activities were combined with outdoor playing time to achieve a proxy of total PA level of moderate to vigorous intensity. Results: Linear regression analyses revealed that at follow-up the intervention...... group spent more time on sports and outdoor activities combined per week than the control group (ITT analyses: intervention: 400 min/week; 95% confidence interval (CI): 341, 459 versus control: 321 min/week; 95% CI: 277, 366; p = 0.02), although no significant intervention effects were seen for each...

  20. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

    2013-01-01

    performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. CONCLUSION: Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes......AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. METHODS: In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study...

  1. Equilibrium sampling of environmental pollutants in fish: Comparison with lipid- normalized concentrations and homogenization effects on chemical activity

    DEFF Research Database (Denmark)

    Jahnke, Annika; Mayer, Philipp; Adolfsson-Erici, Margaretha

    2011-01-01

    of the equilibrium sampling technique, while at the same time confirming that the fugacity capacity of these lipid-rich tissues for PCBs was dominated by the lipid fraction. Equilibrium sampling was also applied to homogenates of the same fish tissues. The PCB concentrations in the PDMS were 1.2 to 2.0 times higher...... in the homogenates (statistically significant in 18 of 21 cases, phomogenization increased the chemical activity of the PCBs and decreased the fugacity capacity of the tissue. This observation has implications for equilibrium sampling and partition coefficients determined using tissue...... homogenates....

  2. The C. elegans H3K27 Demethylase UTX-1 Is Essential for Normal Development, Independent of Its Enzymatic Activity

    DEFF Research Database (Denmark)

    Vandamme, Julien; Buchhorn, Gaëlle Lettier; Sidoli, Simone

    2012-01-01

    specific for H3K27me2/3. We demonstrate that utx-1 is an essential gene that is required for correct embryonic and postembryonic development. Consistent with its homology to UTX, UTX-1 regulates global levels of H3K27me2/3 in C. elegans. Surprisingly, we found that the catalytic activity is not required......Epigenetic modifications influence gene expression and provide a unique mechanism for fine-tuning cellular differentiation and development in multicellular organisms. Here we report on the biological functions of UTX-1, the Caenorhabditis elegans homologue of mammalian UTX, a histone demethylase...

  3. Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.

    Science.gov (United States)

    Wang, Zhongxiao; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Favazza, Tara L; Morss, Peyton C; Saba, Nicholas J; Fredrick, Thomas W; He, Xi; Akula, James D; Chen, Jing

    2016-10-01

    Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

    International Nuclear Information System (INIS)

    Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

    1988-01-01

    Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

  5. EEG activation differences in the pre-motor cortex and supplementary motor area between normal individuals with high and low traits of autism.

    Science.gov (United States)

    Puzzo, Ignazio; Cooper, Nicholas R; Vetter, Petra; Russo, Riccardo

    2010-06-25

    The human mirror neuron system (hMNS) is believed to provide a basic mechanism for social cognition. Event-related desynchronization (ERD) in alpha (8-12Hz) and low beta band (12-20Hz) over sensori-motor cortex has been suggested to index mirror neurons' activity. We tested whether autistic traits revealed by high and low scores on the Autistic Quotient (AQ) in the normal population are linked to variations in the electroencephalogram (EEG) over motor, pre-motor cortex and supplementary motor area (SMA) during action observation. Results revealed that in the low AQ group, the pre-motor cortex and SMA were more active during hand action than static hand observation whereas in the high AQ group the same areas were active both during static and hand action observation. In fact participants with high traits of autism showed greater low beta ERD while observing the static hand than those with low traits and this low beta ERD was not significantly different when they watched hand actions. Over primary motor cortex, the classical alpha and low beta ERD during hand actions relative to static hand observation was found across all participants. These findings suggest that the observation-execution matching system works differently according to the degree of autism traits in the normal population and that this is differentiated in terms of the EEG according to scalp site and bandwidth. Copyright 2010 Elsevier B.V. All rights reserved.

  6. Left ventricular function impairment in patients with normal-weight obesity: contribution of abdominal fat deposition, profibrotic state, reduced insulin sensitivity, and proinflammatory activation.

    Science.gov (United States)

    Kosmala, Wojciech; Jedrzejuk, Diana; Derzhko, Roksolana; Przewlocka-Kosmala, Monika; Mysiak, Andrzej; Bednarek-Tupikowska, Grazyna

    2012-05-01

    Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. One hundred sixty-eight subjects (age, 38±7 years) with BMI affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (β=-0.17, P<0.006), C-reactive protein (β=-0.20, P<0.002) and abdominal fat deposit (β=-0.20, P<0.003); for tissue S velocity, PICP (β=-0.21, P<0.002) and abdominal fat deposit (β=-0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (β=-0.30, P<0.0001), PICP (β=-0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; β=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both β=0.18, P<0.01) and HOMA IR (β=0.16, P<0.04). In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

  7. Whole grain wheat sourdough bread does not affect plasminogen activator inhibitor-1 in adults with normal or impaired carbohydrate metabolism.

    Science.gov (United States)

    MacKay, K A; Tucker, A J; Duncan, A M; Graham, T E; Robinson, L E

    2012-09-01

    Epidemiological studies suggest whole grain consumption is associated with a reduced risk of cardiovascular disease (CVD), possibly through alterations in glucose metabolism and subsequent effects on plasminogen activator inhibitor (PAI)-1, a novel biomarker for CVD. Our aim was to investigate the effect of 6 wk of whole grain wheat sourdough bread consumption versus refined white bread on PAI-1. Normoglycemic/normoinsulinemic (NGI; n = 14; age 53 ± 6 y; BMI 26.5 ± 2.9 kg/m(2)) and hyperglycemic/hyperinsulinemic (HGI; n = 14; age 57 ± 7 y; BMI 35.7 ± 5.7 kg/m(2)) adults incorporated whole grain wheat sourdough (162.5 g) or white (168.8 g) bread into their diet, for 6 wk in a randomized crossover study. Pre- and post-intervention, fasting blood samples were analyzed for PAI-1 (primary outcome), as well as glucose, insulin and glucagon (secondary outcomes) at fasting and postprandially after an oral glucose tolerance test (OGTT). Anthropometric measures, fasting glucose, insulin, glucagon and PAI-1 antigen and activity were not different between treatments in either NGI or HGI adults. Glucose incremental area under the curve (iAUC) was lower (19%, P = 0.02) after 6 wk consumption of whole grain wheat sourdough bread compared to white bread in the HGI group, with no differences in insulin or glucagon iAUC in either group. Our data showed decreased glucose iAUC after an OGTT following 6 wk whole grain wheat bread consumption in adults with differing glycemic/insulinemic status, but no improvements in PAI-1 or fasting glycemic parameters. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Achieving a predictable 24-hour return to normal activities after breast augmentation: part II. Patient preparation, refined surgical techniques, and instrumentation.

    Science.gov (United States)

    Tebbetts, John B

    2006-12-01

    The goal of this study was to develop practices that would allow patients undergoing subpectoral augmentation to predictably return to full normal activities within 24 hours after the operation, free of postoperative adjuncts. Part I of this study used motion and time study principles to reduce operative times, medication dosages, perioperative morbidity, and recovery times in augmentation mammaplasty. Part II of the study focuses on details of patient education, preoperative planning, instrumentation, and surgical technique modifications that were identified, modified, and implemented to achieve the results reported in part I. Two groups of 16 patients each (groups 1 and 2) were studied retrospectively for comparison to a third group of 627 patients (group 3) studied prospectively. Patients in group 1 had axillary partial retropectoral breast augmentations in 1982-1983, using dissociative anesthesia, blunt instrument implant pocket dissection, and Dow Corning, double-lumen implants containing 20 mg of methylprednisolone and 20 cc of saline in the outer lumen of the implants. Patients in group 2 (1990) had inframammary, retromammary augmentations by using a combination of blunt and electrocautery dissection, Surgitek Replicon polyurethane-covered, silicone gel-filled implants, and general endotracheal anesthesia. Patients in group 3 (1998 to 2001, n = 627) had inframammary partial retropectoral, inframammary retromammary, and axillary partial retropectoral augmentations under general endotracheal anesthesia. Refined practices and surgical techniques from studies of groups 1 and 2 were applied in group 3. Videotapes from operative procedures of groups 1 and 2 were analyzed with macromotion and micromotion study principles, and tables of events were formulated for each move during the operation for all personnel in the operating room. Extensive details of surgical technique were examined and reexamined in 13 different stages by using principles of motion and time

  9. Pontas evocadas por estímulos somatossensitivos e atividade epileptiforme no eletrencefalograma em crianças "normais" Somatosensory evoked spikes and epileptiform activity in "normal" children

    Directory of Open Access Journals (Sweden)

    Lineu C. Fonseca

    2003-09-01

    Full Text Available Estudamos a ocorrência de potenciais de alta voltagem evocados por estímulos somatossensitivos - pontas evocadas (PE - e de atividade epileptiforme espontânea (AE no EEG de 173 crianças normais de 7 a 11 anos de idade. Durante o EEG, dez percussões foram realizadas nas mãos e pés. Foi avaliada a ocorrência de PE acompanhando cada um dos estímulos e a presença de AE. AE foi observada em quatro crianças (2,3%: pontas centroparietais em duas, complexos de ponta-onda lenta generalizados em uma e pontas parietais e temporais médias em uma. Uma menina de 10 anos de idade (0,58% teve ao EEG pontas parietais medianas evocadas pela percussão do pé esquerdo. Este EEG era normal quanto a outros aspectos. Nossos achados de AE em crianças normais são similares aos encontrados em estudos de outros países. Constatamos que espículas somatossensitivas podem ser observadas em crianças normais o que sugere uma natureza funcional ligada à idade.Little is known about somatosensory evoked spikes (SES in the EEG of normal children. We studied the occurrence of SES and spontaneous epileptiform activity (SEA in 173 normal children ageg 7 to 11 years. During the EEG ten taps were applied to both hands and feet. The occurrence of high voltage potentials evoked by each stimulation of one or both heels or hands (SES and the occurrence of SEA were evaluated. SEA was observed in four children (2.3 %: central/parietal spikes in two cases, generalized spike-and-wave in one, and parietal/midtemporal spikes in one case. A ten years old girl (0,58% had SES on median parietal region by tapping the left foot. This EEG was otherwise normal. Our findings of SEA are similar to those obtained in other normal populations. SES can be observed in normal children. These SES suggest that we are dealing with an age-related functional phenomenon.

  10. The in vivo neutron activation analysis of calcium in the skeleton of normal subjects, with hypokinesia and bone diseases

    International Nuclear Information System (INIS)

    Zaichick, V.Ye.

    1993-01-01

    A facility developed for the in-vivo neutron activation analysis (IVNAA) of calcium in some parts of tubular limb bones, in the hand, foot and spine is described. The 48 Ca(n,γ) 49 Ca reaction is used, the gamma-rays of 49 Ca (Eγ = 3.08 MeV, T 1/2 = 8.8 min) are measured. The irradiation is carried out with five of ten 238 Pu-Be neutron sources with a source strength of 5*10 7 n s -1 each arranged in a bath filled with water. NaI(Tl) detectors (from 2 to 4 in number) of 150 * 100 mm size supplied with lead and shadow shielding are used in counting unit. The construction of the facility started in 1972 and has been in operation since 1974. It has been used for the examination of patients suffering from limb bone tumors, of children with rickets-like and similar diseases and for studies in space medicine. (author) 20 refs.; 5 figs.; 2 tabs

  11. Normal autophagic activity in macrophages from mice lacking Gαi3, AGS3, or RGS19.

    Directory of Open Access Journals (Sweden)

    Ali Vural

    Full Text Available In macrophages autophagy assists antigen presentation, affects cytokine release, and promotes intracellular pathogen elimination. In some cells autophagy is modulated by a signaling pathway that employs Gαi3, Activator of G-protein Signaling-3 (AGS3/GPSM1, and Regulator of G-protein Signaling 19 (RGS19. As macrophages express each of these proteins, we tested their importance in regulating macrophage autophagy. We assessed LC3 processing and the formation of LC3 puncta in bone marrow derived macrophages prepared from wild type, Gnai3(-/-, Gpsm1(-/-, or Rgs19(-/- mice following amino acid starvation or Nigericin treatment. In addition, we evaluated rapamycin-induced autophagic proteolysis rates by long-lived protein degradation assays and anti-autophagic action after rapamycin induction in wild type, Gnai3(-/-, and Gpsm1(-/- macrophages. In similar assays we compared macrophages treated or not with pertussis toxin, an inhibitor of GPCR (G-protein couple receptor triggered Gαi nucleotide exchange. Despite previous findings, the level of basal autophagy, autophagic induction, autophagic flux, autophagic degradation and the anti-autophagic action in macrophages that lacked Gαi3, AGS3, or RGS19; or had been treated with pertussis toxin, were similar to controls. These results indicate that while Gαi signaling may impact autophagy in some cell types it does not in macrophages.

  12. Restoration of normal pH triggers ischemia-reperfusion injury in lung by Na+/H+ exchange activation.

    Science.gov (United States)

    Moore, T M; Khimenko, P L; Taylor, A E

    1995-10-01

    The effects of acidotic extracellular pH and Na+/H+ exchange inhibition on ischemia-reperfusion (I/R)-induced microvascular injury were studied in the isolated, buffer-perfused rat lung. When lungs were subjected to 45 min of ischemia followed by 30 min of reperfusion, the capillary filtration coefficient (Kfc) increased significantly, resulting in a change in Kfc (delta Kfc) of 0.360 +/- 0.09 ml.min-1.cmH2O-1.100 g-1. Addition of hydrochloric acid to the perfusate before ischemia at a concentration sufficient to reduce perfusate pH from 7.38 +/- 0.03 to 7.09 +/- 0.04 completely prevented the increase in Kfc associated with I/R (delta Kfc = 0.014 +/- 0.034 ml.min-1.cmH2O-1.100 g-1). Addition of a Na+/H+ exchange inhibitor, 5-(N,N-dimethyl)-amiloride, to the perfusate either before ischemia or at reperfusion also prevented the I/R-induced permeability increase (delta Kfc = 0.01 +/- 0.02 and -0.001 +/- 0.02 ml.min-1.cmH2O-1.100 g-1, respectively). We conclude that restoration of flow at physiological pH to the postischemic lung activates the Na+/H+ exchange system, which may represent the "triggering mechanism" responsible for initiating reperfusion-induced microvascular injury.

  13. ENU mutagenesis screening for dominant behavioral mutations based on normal control data obtained in home-cage activity, open-field, and passive avoidance tests.

    Science.gov (United States)

    Wada, Yumiko; Furuse, Tamio; Yamada, Ikuko; Masuya, Hiroshi; Kushida, Tomoko; Shibukawa, Yoko; Nakai, Yuji; Kobayashi, Kimio; Kaneda, Hideki; Gondo, Yoichi; Noda, Tetsuo; Shiroishi, Toshihiko; Wakana, Shigeharu

    2010-01-01

    To establish the cutoff values for screening ENU-induced behavioral mutations, normal variations in mouse behavioral data were examined in home-cage activity (HA), open-field (OF), and passive-avoidance (PA) tests. We defined the normal range as one that included more than 95% of the normal control values. The cutoffs were defined to identify outliers yielding values that deviated from the normal by less than 5% for C57BL/6J, DBA/2J, DBF(1), and N(2) (DXDB) progenies. Cutoff values for G1-phenodeviant (DBF(1)) identification were defined based on values over +/- 3.0 SD from the mean of DBF(1) for all parameters assessed in the HA and OF tests. For the PA test, the cutoff values were defined based on whether the mice met the learning criterion during the 2nd (at a shock intensity of 0.3 mA) or the 3rd (at a shock intensity of 0.15 mA) retention test. For several parameters, the lower outliers were undetectable as the calculated cutoffs were negative values. Based on the cutoff criteria, we identified 275 behavioral phenodeviants among 2,646 G1 progeny. Of these, 64 were crossed with wild-type DBA/2J individuals, and the phenotype transmission was examined in the G2 progeny using the cutoffs defined for N(2) mice. In the G2 mice, we identified 15 novel dominant mutants exhibiting behavioral abnormalities, including hyperactivity in the HA or OF tests, hypoactivity in the OF test, and PA deficits. Genetic and detailed behavioral analysis of these ENU-induced mutants will provide novel insights into the molecular mechanisms underlying behavior.

  14. Technetium labelled plasminogen activator - a potential reagent for thrombus detection

    Energy Technology Data Exchange (ETDEWEB)

    Paulsma-De Waal, J.H.; Boer, A.C. de; Cox, P.H.; Pillay, M.; Stassen, J.H.; Collen, D.

    1987-12-01

    The preparation of a technetium labelled plasminogen activator complex using a solid phase labelling technique is described. The labelled complex showed no significant loss of fibrinolytic activity in vitro and showed in vivo a rapid uptake in thrombi in an animal model and in human volunteer patients with known thrombi when injected into a vein draining to the thrombotic region. Systemic injection showed no uptake in the thrombi probably due to rapid sequestration of the complex by the liver.

  15. Connexin 39.9 Protein Is Necessary for Coordinated Activation of Slow-twitch Muscle and Normal Behavior in Zebrafish*

    Science.gov (United States)

    Hirata, Hiromi; Wen, Hua; Kawakami, Yu; Naganawa, Yuriko; Ogino, Kazutoyo; Yamada, Kenta; Saint-Amant, Louis; Low, Sean E.; Cui, Wilson W.; Zhou, Weibin; Sprague, Shawn M.; Asakawa, Kazuhide; Muto, Akira; Kawakami, Koichi; Kuwada, John Y.

    2012-01-01

    In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for myogenesis. Although gap junctions were once believed to be absent from differentiated skeletal muscle in mammals, recent studies in teleosts revealed that differentiated muscle does express connexins and is electrically coupled, at least at the larval stage. These findings raised questions regarding the functional significance of gap junctions in differentiated muscle. Our analysis of gap junctions in muscle began with the isolation of a zebrafish motor mutant that displayed weak coiling at day 1 of development, a behavior known to be driven by slow-twitch muscle (slow muscle). We identified a missense mutation in the gene encoding Connexin 39.9. In situ hybridization found connexin 39.9 to be expressed by slow muscle. Paired muscle recordings uncovered that wild-type slow muscles are electrically coupled, whereas mutant slow muscles are not. The further examination of cellular activity revealed aberrant, arrhythmic touch-evoked Ca2+ transients in mutant slow muscle and a reduction in the number of muscle fibers contracting in response to touch in mutants. These results indicate that Connexin 39.9 facilitates the spreading of neuronal inputs, which is irregular during motor development, beyond the muscle cells and that gap junctions play an essential role in the efficient recruitment of slow muscle fibers. PMID:22075003

  16. Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

    Science.gov (United States)

    Watabe, Tadashi; Naka, Sadahiro; Ikeda, Hayato; Horitsugi, Genki; Kanai, Yasukazu; Isohashi, Kayako; Ishibashi, Mana; Kato, Hiroki; Shimosegawa, Eku; Watabe, Hiroshi; Hatazawa, Jun

    2014-01-01

    Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11)C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. The distribution of (11)C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11)C-DNP (45.0 ± 10.7 MBq). The whole-body distribution of the (11)C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11)C-DNP in the body (following the liver) (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3), respectively), indicating that the distribution of (11)C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. We demonstrated the whole-body distribution of (11)C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11)C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

  17. Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

    Directory of Open Access Journals (Sweden)

    Tadashi Watabe

    Full Text Available PURPOSE: Acetylcholinesterase (AChE inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11C-Donepezil (DNP and the AChE activity in the normal rat, with special focus on the adrenal glands. METHODS: The distribution of (11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g. A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11C-DNP (45.0 ± 10.7 MBq. The whole-body distribution of the (11C-DNP PET was evaluated based on the Vt (total distribution volume by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. RESULTS: The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11C-DNP in the body (following the liver (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3, respectively, indicating that the distribution of (11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively, indicating high activity of AChE in the adrenal glands. CONCLUSIONS: We demonstrated the whole-body distribution of (11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

  18. Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

    International Nuclear Information System (INIS)

    Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena; Mishto, Michele; Santoro, Aurelia; Fiorentino, Michelangelo; Capri, Miriam; Cescon, Matteo; Grazi, Gian Luca; Grigioni, Walter Franco; D'Errico-Grigioni, Antonia; Franceschi, Claudio

    2010-01-01

    Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive (α4 and β1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28αβ regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28αβ. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

  19. Studies on immunoproteasome in human liver. Part I: Absence in fetuses, presence in normal subjects, and increased levels in chronic active hepatitis and cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Vasuri, Francesco; Capizzi, Elisa [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Bellavista, Elena [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Mishto, Michele [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Institute of Biochemistry, Medical Faculty Charite, Berlin (Germany); Santoro, Aurelia [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Fiorentino, Michelangelo [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Capri, Miriam [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy); Cescon, Matteo; Grazi, Gian Luca [Unit of General and Transplantation Surgery, S.Orsola-Malpighi Hospital, Bologna University (Italy); Grigioni, Walter Franco; D' Errico-Grigioni, Antonia [Pathology Unit of the ' F. Addarii' Institute of Oncology, S.Orsola-Malpighi Hospital, Bologna University (Italy); Franceschi, Claudio, E-mail: claudio.franceschi@unibo.it [Department of Experimental Pathology, Bologna University (Italy); Interdepartmental Center for Studies on Biophysics, Bioinformatics and Biocomplexity ' L. Galvani' (CIG), Bologna University (Italy)

    2010-06-25

    Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical data have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.

  20. Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction - A double-blind, randomized angiographic trial of lanoteplase versus alteplase

    NARCIS (Netherlands)

    den Heijer, P; Vermeer, F; Ambrosioni, E; Sadowski, Z; Lopez-Sendon, JL; von Essen, R; Beaufils, P; Thadani, U; Adgey, J; Pierard, L; Brinker, J; Davies, RF; Smalling, RW; Wallentin, L; Caspi, A; Pangerl, A; Trickett, L; Hauck, C; Henry, D; Chew, P

    1998-01-01

    Background-Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. Methods and Results-InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind,

  1. [Effect of Mn(II) on the error-prone DNA polymerase iota activity in extracts from human normal and tumor cells].

    Science.gov (United States)

    Lakhin, A V; Efremova, A S; Makarova, I V; Grishina, E E; Shram, S I; Tarantul, V Z; Gening, L V

    2013-01-01

    The DNA polymerase iota (Pol iota), which has some peculiar features and is characterized by an extremely error-prone DNA synthesis, belongs to the group of enzymes preferentially activated by Mn2+ instead of Mg2+. In this work, the effect of Mn2+ on DNA synthesis in cell extracts from a) normal human and murine tissues, b) human tumor (uveal melanoma), and c) cultured human tumor cell lines SKOV-3 and HL-60 was tested. Each group displayed characteristic features of Mn-dependent DNA synthesis. The changes in the Mn-dependent DNA synthesis caused by malignant transformation of normal tissues are described. It was also shown that the error-prone DNA synthesis catalyzed by Pol iota in extracts of all cell types was efficiently suppressed by an RNA aptamer (IKL5) against Pol iota obtained in our work earlier. The obtained results suggest that IKL5 might be used to suppress the enhanced activity of Pol iota in tumor cells.

  2. Peroxisome proliferator-activated receptor α agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    International Nuclear Information System (INIS)

    Antonelli, Alessandro; Ferrari, Silvia Martina; Frascerra, Silvia; Corrado, Alda; Pupilli, Cinzia; Bernini, Giampaolo; Benvenga, Salvatore; Ferrannini, Ele; Fallahi, Poupak

    2011-01-01

    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR)α activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPARα and PPARγ activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN)γ and tumor necrosis factor (TNF)α. IFNγ stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNFα alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFNγ and TNFα had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPARα activators inhibited the secretion of both chemokines (stimulated with IFNγ and TNFα) at a level higher (for CXCL10, about 60-72%) than PPARγ agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFNγ and TNFα in GD and normal thyrocytes. Furthermore we first show that PPARα activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPARα may be involved in the modulation of the immune response in the thyroid.

  3. [Change in the activity of natural killer cells in normal subjects and in virus diseases on exposure to interferon in vitro].

    Science.gov (United States)

    Petrov, R V; Saidov, M Z; Koval'chuk, L V; Sorokin, A M; Kaganov, B S

    1984-04-01

    The activity of natural killers was examined in peripheral blood of healthy subjects and patients with chronic hepatitis and disseminated sclerosis. An attempt was made to correct natural killer activity by human leukocyte interferon in vitro. To assess the activity of natural killers, use was made of the method of serial dilutions. An optimal effector/target ratio was employed in experiments. The patients with chronic hepatitis and disseminated sclerosis demonstrated a reduction in the activity of natural killers whatever the effector/target ratio. The action of interferon in vitro is specific immunomodulatory in nature. Administration of interferon in a dose of 250 Units/ml raises the magnitude of the cytotoxic index in healthy donors and in patients with chronic hepatitis and disseminated sclerosis, making the shape of the killer activity curve approach that of normal. Such an approach can be used for preliminary assessment of the sensitivity of natural killers to interferon in viral diseases of man. The potentialities and efficacy of interferon in clinical medicine are discussed.

  4. The rarity of ALDH(+) cells is the key to separation of normal versus leukemia stem cells by ALDH activity in AML patients.

    Science.gov (United States)

    Hoang, Van T; Buss, Eike C; Wang, Wenwen; Hoffmann, Isabel; Raffel, Simon; Zepeda-Moreno, Abraham; Baran, Natalia; Wuchter, Patrick; Eckstein, Volker; Trumpp, Andreas; Jauch, Anna; Ho, Anthony D; Lutz, Christoph

    2015-08-01

    To understand the precise disease driving mechanisms in acute myeloid leukemia (AML), comparison of patient matched hematopoietic stem cells (HSC) and leukemia stem cells (LSC) is essential. In this analysis, we have examined the value of aldehyde dehydrogenase (ALDH) activity in combination with CD34 expression for the separation of HSC from LSC in 104 patients with de novo AML. The majority of AML patients (80 out of 104) had low percentages of cells with high ALDH activity (ALDH(+) cells; cells (≥1.9%; ALDH-numerous AML). In patients with ALDH-rare AML, normal HSC could be separated by their CD34(+) ALDH(+) phenotype, whereas LSC were exclusively detected among CD34(+) ALDH(-) cells. For patients with ALDH-numerous AML, the CD34(+) ALDH(+) subset consisted mainly of LSC and separation from HSC was not feasible. Functional analyses further showed that ALDH(+) cells from ALDH-numerous AML were quiescent, refractory to ARA-C treatment and capable of leukemic engraftment in a xenogenic mouse transplantation model. Clinically, resistance to chemotherapy and poor long-term outcome were also characteristic for patients with ALDH-numerous AML providing an additional risk-stratification tool. The difference in spectrum and relevance of ALDH activity in the putative LSC populations demonstrates, in addition to phenotypic and genetic, also functional heterogeneity of leukemic cells and suggests divergent roles for ALDH activity in normal HSC versus LSC. By acknowledging these differences our study provides a new and useful tool for prospective identification of AML cases in which separation of HSC from LSC is possible. © 2014 UICC.

  5. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Walker Mark

    2010-11-01

    Full Text Available Abstract Background Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. Methods This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2 recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. Results Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32] and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86] than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]. A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]. Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. Conclusion A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that

  6. Differences in energy expenditure, amount of physical activity and physical exertion level during a Zumba fitness class among adult women who are normal weight, overweight and obese.

    Science.gov (United States)

    Yáñez-Sepúlveda, Rodrigo; Barraza-Gómez, Fernando; Báez-San Martin, Eduardo; Araneda, Oscar F; Zavala, Juan P; Hecht, Gernot K; Tuesta, Marcelo

    2018-01-01

    One of the most popular expressions of massive group classes of aerobic physical activity is Zumba fitness. The aim of the study was to compare and relate the energy expenditure and the amount and intensity of physical effort during a Zumba fitness class in women with different Body Mass Index (BMI). Body displacements of 61 adult women who performed a one-hour Zumba session were evaluated with triaxial accelerometers. In order to observe the effect of BMI women were divided into normal weight (N.=26), overweight (N.=21) and obese groups (N.=14). The average number of steps was 4533.3±1351 and the percentage of total class time of moderate to vigorous intensity (% MVPA) was 53.8±14.4%. The metabolic intensity average was 3.64±1.1 MET, with an energy expenditure by total body mass of 3.9±1.6 kcal/kg. When analyzing groups, the normal weight group had a greater number of steps (5184.2±1561.1 steps/class) compared to overweight (4244.8±1049.3 steps/class) and obese women (3756.9±685.7 steps/class) with Plower percentage of class time at the lower levels of intensity (sedentary and lifestyle activity levels) and more time at the highest levels (vigorous and very vigorous) compared to obese women (Plower energy expenditure values per kilo of weight (r=-0.40; Plower intensity of effort, energy expenditure and amount of physical activity during a one-hour Zumba class, restricting to overweight and obese women to achieving the effort parameters recommended to control weight and improve cardiovascular fitness.

  7. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension.

    Science.gov (United States)

    Nyberg, M; Mortensen, S P; Hellsten, Y

    2013-03-01

    Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension and age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had performed lifelong physical activity had similar plasma and muscle endothelin-1 levels as the young controls and had higher ET(A) receptor levels. Our findings suggest that aerobic exercise training opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension. This effect may explain some of the beneficial effects of training on the cardiovascular system in older and hypertensive subjects. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

  8. Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

    Science.gov (United States)

    Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

    2011-09-01

    This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Regular activity breaks combined with physical activity improve postprandial plasma triglyceride, nonesterified fatty acid, and insulin responses in healthy, normal weight adults: A randomized crossover trial.

    Science.gov (United States)

    Homer, Ashleigh R; Fenemor, Stephen P; Perry, Tracy L; Rehrer, Nancy J; Cameron, Claire M; Skeaff, C Murray; Peddie, Meredith C

    Compared with prolonged sitting, regular activity breaks immediately lower postprandial glucose and insulin, but not triglyceride responses. Postprandial triglycerides can be lowered by physical activity but the effect is often delayed by ∼12 to 24 hours. The objective of the study was to determine whether regular activity breaks affect postprandial triglyceride response in a delayed manner similar to physical activity. In a randomized crossover trial, 36 adults (body mass index 23.9 kg/m 2 [standard deviation 3.9]) completed four 2-day interventions: (1) prolonged sitting (SIT); (2) prolonged sitting with 30 minutes of continuous walking (60% VO 2max ), at the end of Day 1 (SIT + PA D1 ); (3) Sitting with 2 minutes of walking (60% VO 2max ) every 30 minutes (RAB); (4) A combination of the continuous walking and regular activity breaks in 2 and 3 above (RAB + PA D1 ). Postprandial plasma triglyceride, nonesterified fatty acids, glucose, and insulin responses were measured in venous blood over 5 hours on Day 2. Compared with SIT, both RAB (difference: -43.61 mg/dL·5 hours; 95% confidence interval [CI] -83.66 to -2.67; P = .035) and RAB + PA D1 (-65.86 mg/dL·5 hours; 95% CI -112.14 to -19.58; P = .005) attenuated triglyceride total area under the curve (tAUC). RAB + PA D1 produced the greatest reductions in insulin tAUC (-23%; 95% CI -12% to -31%; P glucose tAUC (P = .290). Postprandial triglyceride response is attenuated by regular activity breaks, when measured ∼24 hours after breaks begin. Combining regular activity breaks with 30 minutes of continuous walking further improves insulinemic and lipidemic responses. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  10. Human Papillomavirus 16 (HPV-16), HPV-18, and HPV-31 E6 Override the Normal Phosphoregulation of E6AP Enzymatic Activity.

    Science.gov (United States)

    Thatte, Jayashree; Banks, Lawrence

    2017-11-15

    The human papillomavirus (HPV) E6 oncoproteins recruit the cellular ubiquitin ligase E6AP/UBE3A to target cellular substrates for proteasome-mediated degradation, and one consequence of this activity is the E6 stimulation of E6AP autoubiquitination and degradation. Recent studies identified an autism-linked mutation within E6AP at T485, which was identified as a protein kinase A phosphoacceptor site and which could directly regulate E6AP ubiquitin ligase activity. In this study, we have analyzed how T485-mediated regulation of E6AP might affect E6 targeting of some of its known substrates. We show that modulation of T485 has no effect on the ability of E6 to direct either p53 or Dlg for degradation. Furthermore, T485 regulation has no effect on HPV-16 or HPV-31 E6-induced autodegradation of E6AP but does affect HPV-18 E6-induced autodegradation of E6AP. In cells derived from cervical cancers, we find low levels of both phosphorylated and nonphosphorylated E6AP in the nucleus. However, ablation of E6 results in a dramatic accumulation of phospho-E6AP in the cytoplasm, whereas nonphosphorylated E6AP accumulates primarily in the nucleus. Interestingly, E6AP phosphorylation at T485 confers association with 14-3-3 proteins, and this interaction seems to be important, in part, for the ability of E6 to recruit phospho-E6AP into the nucleus. These results demonstrate that HPV E6 overrides the normal phosphoregulation of E6AP, both in terms of its enzymatic activity and its subcellular distribution. IMPORTANCE Recent reports demonstrate the importance of phosphoregulation of E6AP for its normal enzymatic activity. Here, we show that HPV E6 is capable of overriding this regulation and can promote degradation of p53 and Dlg regardless of the phosphorylation status of E6AP. Furthermore, E6 interaction with E6AP also significantly alters how E6AP is subject to autodegradation and suggests that this is not a simple stimulation of an already-existing activity but rather a

  11. Evaluation of an in vivo prompt gamma neutron activation facility for body composition studies in critically ill intensive care patients: results on 41 normals

    International Nuclear Information System (INIS)

    Beddoe, A.H.; Streat, S.J.; Hill, G.L.

    1984-01-01

    A programme of metabolic and nutritional research is being undertaken in critically ill patients requiring intensive care. Central to this research is the measurement of the three nutritionally important compartments of body composition, protein, fat, and water by a combination of tritium dilution and prompt gamma in vivo neutron activation analysis (IVNAA). In this paper a calibration technique is presented that enables absolute estimates of total body nitrogen (TBN) to be made using prompt gamma IVNAA in critically ill patients with gross abnormalities in body composition, especially in their state of hydration. This technique, which is independent of skinfold anthropometry and does not make a priori assumptions about the ratios of major body compartments, has been applied to 41 normal volunteers and the derived values for nitrogen compared with values obtained by applying three currently used calibration methods to the same experimental data. The empirical equations relate TBN in normal people to age, height, weight and sex. The mean ratios of experimental to predicted TBN (with SEMs) are 1.013 +/- 0.017 and 1.002 +/- 0.014, respectively. Mean values of the ratio of TBN to fat-free mass (0.0340 +/- 0.0004) and of total body water to fat-free mass (0.716 +/- 0.002) agree closely with values reported elsewhere for normals by a variety of techniques including chemical analysis. Finally, TBN results based on the four different calibration methods are presented for five surgical patients, demonstrating the importance of the calibration method on estimates of TBN in patients with abnormal body composition. It is concluded that this technique will provide accurate estimates of the total body content of protein, water, and fat in intensive care patients

  12. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    Science.gov (United States)

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-04-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Geomorphological evolution of landslides near an active normal fault in northern Taiwan, as revealed by lidar and unmanned aircraft system data

    Science.gov (United States)

    Chang, Kuo-Jen; Chan, Yu-Chang; Chen, Rou-Fei; Hsieh, Yu-Chung

    2018-03-01

    Several remote sensing techniques, namely traditional aerial photographs, an unmanned aircraft system (UAS), and airborne lidar, were used in this study to decipher the morphological features of obscure landslides in volcanic regions and how the observed features may be used for understanding landslide occurrence and potential hazard. A morphological reconstruction method was proposed to assess landslide morphology based on the dome-shaped topography of the volcanic edifice and the nature of its morphological evolution. Two large-scale landslides in the Tatun volcano group in northern Taiwan were targeted to more accurately characterize the landslide morphology through airborne lidar and UAS-derived digital terrain models and images. With the proposed reconstruction method, the depleted volume of the two landslides was estimated to be at least 820 ± 20 × 106 m3. Normal faulting in the region likely played a role in triggering the two landslides, because there are extensive geological and historical records of an active normal fault in this region. The subsequent geomorphological evolution of the two landslides is thus inferred to account for the observed morphological and tectonic features that are indicative of resulting in large and life-threatening landslides, as characterized using the recent remote sensing techniques.

  14. Cell structure and proliferative activity of organ cultures of normal embryonic lung tissue of mice resistant (C57BL) and predisposed (A) to lung tumors

    International Nuclear Information System (INIS)

    Kolesnichenko, T.S.; Gor'kova, T.G.

    1985-01-01

    Local factors such as proliferative activity and the numerical ratio between epithelial and mesenchymal cells, and also the character of interaction between the tissue components in ontogeny may play an important role in the realization of sensitivity of mice of a particular line to the development of lung tumors. These characteristics of lung tissue in mice of lines A and C57BL are investigated under normal conditions and during induced carcinogenesis. Results are given of a comparative study of the relative numbers of epithelial and mesenchymal cells in organ cultures of embryonic lungs. 3 H-thymidine was added to the cultures on the 14th day of the experiment in a concentration of 1 microCi/m1 medium. An autoradiographic study of the cultures was performed

  15. Peroxisome proliferator-activated receptor {alpha} agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Alessandro, E-mail: a.antonelli@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Ferrari, Silvia Martina, E-mail: sm.ferrari@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Frascerra, Silvia, E-mail: lafrasce@gmail.com [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Corrado, Alda, E-mail: dala_res@hotmail.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Pupilli, Cinzia, E-mail: c.pupilli@dfc.unifi.it [Endocrinology Unit, Azienda Ospedaliera Careggi and University of Florence, Viale Morgagni 85, I-50134, Florence (Italy); Bernini, Giampaolo, E-mail: g.bernini@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Benvenga, Salvatore, E-mail: s.benvenga@me.nettuno.it [Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti 1, I-98122, Messina (Italy); Ferrannini, Ele, E-mail: eferrannini@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Fallahi, Poupak, E-mail: poupak@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy)

    2011-07-01

    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR){alpha} activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPAR{alpha} and PPAR{gamma} activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN){gamma} and tumor necrosis factor (TNF){alpha}. IFN{gamma} stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNF{alpha} alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFN{gamma} and TNF{alpha} had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPAR{alpha} activators inhibited the secretion of both chemokines (stimulated with IFN{gamma} and TNF{alpha}) at a level higher (for CXCL10, about 60-72%) than PPAR{gamma} agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFN{gamma} and TNF{alpha} in GD and normal thyrocytes. Furthermore we first show that PPAR{alpha} activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPAR{alpha} may be involved in the modulation of the immune response in the thyroid.

  16. Efeito da atividade física no osso normal e na prevenção e tratamento da osteoporose Efectos de la actividad física en huesos normales y en la prevención y tratamiento de osteoporosis Effect of the physical activity on normal bone and on the osteoporosis prevention and treatment

    Directory of Open Access Journals (Sweden)

    Natália de Melo Ocarino

    2006-06-01

    Full Text Available A osteoporose é uma doença cada vez mais diagnosticada em mulheres e homens de todo o mundo. Embora os esteróides sexuais sejam importantes na gênese da osteoporose, a inatividade física constitui um fator de risco. O exercício físico atua no osso por efeito direto, via força mecânica, ou indireto, mediado por fatores hormonais. Mas os mecanismos pelos quais a atividade física melhora a massa óssea ainda não são totalmente conhecidos. Baseando-se nos resultados que demonstram os efeitos benéficos da atividade física no tecido ósseo, a prática de esportes vem sendo cada vez mais indicada na prevenção e até mesmo no tratamento da osteoporose. O objetivo desta revisão é descrever os efeitos da atividade física no tecido ósseo normal e na prevenção e tratamento da osteoporose.La osteoporosis es una enfermedad que cada vez más se diagnostica en mujeres y hombres de todo el mundo. Aunque los esteroides sexuales sean importantes en la génesis de la osteoporosis, la inactividad física constituye un factor de riesgo. El ejercicio físico actúa en el hueso de forma directa, vía fuerza mecánica, o indirecta, mediado por factores hormonales. Sin embargo la patogénesis por la que la actividad física mejora la masa ósea todavía no es totalmente conocida. Con base en los resultados que demuestran los efectos benéficos de la actividad física en el tejido óseo, la práctica de deportes viene siendo indicada cada vez más como medio de prevención y hasta incluso como tratamiento de la osteoporosis. El objetivo de esta revisión es describir los efectos de la actividad física en el tejido óseo normal y en la prevención y tratamiento de la osteoporosis.Osteoporosis has been increasingly diagnosed in women and men worldwide. Although the sexual steroids are important in the genesis of human osteoporosis, it is believed that the lack of physical activity constitutes a risk factor. Physical activity acts on the bone by direct

  17. Growth hormone replacement normalizes impaired fibrinolysis: new insights into endothelial dysfunction in patients with hypopituitarism and growth hormone deficiency.

    Science.gov (United States)

    Miljic, D; Miljic, P; Doknic, M; Pekic, S; Stojanovic, M; Cvijovic, G; Micic, D; Popovic, V

    2013-12-01

    Cardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far. To investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement. Hospital based, interventional, prospective study. Twenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI). Anthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH. At baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4-13.5) to 22.0(9.0-33.0) nmol/l after one month of treatment; p<0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4-2.6) to 1.9(0.5-8.8) after one year of treatment; p<0.01]. Growth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications. © 2013.

  18. EFFECT OF MELATONIN DURING THE SEASONAL ANOESTROUS ON THE REACTIVATION OF THE SEXUAL ACTIVITY AND SEMEN PRODUCTION AT THE NORMAL BREEDING SEASON ON MEDITERRANEAN BUCKS

    Directory of Open Access Journals (Sweden)

    Luis Zarazaga

    2009-06-01

    Full Text Available One experiment was conducted to determine if the onset of the reproductive activity and semen production could be modified by a previous treatment with exogenous melatonin, used to enhance reproductive activity during the seasonal anoestrous in Mediterranean bucks. Two balanced groups of bucks were used. The 18th march 2005, one group (M group received 3 s.c. implants of melatonin (N=7 and other group (N=4 was used like control (C group. From June to September, body weight and testosterone was measured weekly and testicular weight every 15 days. The reproductive activity of each buck was assessed using characteristics of the testosterone profile. During the first 8 days of each month, volume of ejaculate and sperm concentration was assessed. Each of these 8-d periods was divided into 3-d periods of daily sperm collection separated by 2 d of rest. The semen was collected using an artificial vagina. The effect of treatment and month was studied on each variable. An interaction, month-treatment was observed on ejaculate volume, July was the month with higher volume (0.62 ± 0.06 mL vs 1.07 ± 0.15 mL for M and C group respectively, P < 0.05. Sperm concentration was influenced by treatment (6.13 x109 ± 2.49 x108 vs 4.26 x109 ± 3.12 x108 sperm/mL, for M and C, respectively, P < 0.05. The onset of the reproductive activity, after the study of the testosterone concentrations was similar for both groups (31st August ± 7.89 days and 4th September ± 25.66 days for M and C group, respectively. Results demonstrate that melatonin treatment during the seasonal anoestrous does not influence the onset of the normal breeding season or ejaculate volume but it seems that could increases the sperm concentration at the normal breeding season in Mediterranean goat males.

  19. eHealth program to empower patients in returning to normal activities and work after gynecological surgery: intervention mapping as a useful method for development.

    Science.gov (United States)

    Vonk Noordegraaf, Antonie; Huirne, Judith A F; Pittens, Carina A; van Mechelen, Willem; Broerse, Jacqueline E W; Brölmann, Hans A M; Anema, Johannes R

    2012-10-19

    Full recovery after gynecological surgery takes much longer than expected regardless of surgical technique or the level of invasiveness. After discharge, detailed convalescence recommendations are not provided to patients typically, and postoperative care is fragmented, poorly coordinated, and given only on demand. For patients, this contributes to irrational beliefs and avoidance of resumption of activities and can result in a prolonged sick leave. To develop an eHealth intervention that empowers gynecological patients during the perioperative period to obtain timely return to work (RTW) and prevent work disability. The intervention mapping (IM) protocol was used to develop the eHealth intervention. A literature search about behavioral and environmental conditions of prolonged sick leave and delayed RTW in patients was performed. Patients' needs, attitudes, and beliefs regarding postoperative recovery and resumption of work were identified through focus group discussions. Additionally, a literature search was performed to obtain determinants, methods, and strategies for the development of a suitable interactive eHealth intervention to empower patients to return to normal activities after gynecological surgery, including work. Finally, the eHealth intervention was evaluated by focus group participants, medical doctors, and eHealth specialists through questionnaires. Twenty-one patients participated in the focus group discussions. Sufficient, uniform, and tailored information regarding surgical procedures, complications, and resumption of activities and work were considered most essential. Knowing who to contact in case of mental or physical complaints, and counseling and tools for work reintegration were also considered important. Finally, opportunities to exchange experiences with other patients were a major issue. Considering the determinants of the Attitude-Social influence-self-Efficacy (ASE) model, various strategies based on a combination of theory and

  20. The proposals on cooperation to foreign centers of science on thermophysical properties of reactor materials in a broad band of pressure and temperatures realized at normal transient and emergency operation activity of nuclear power plants

    International Nuclear Information System (INIS)

    Fortov, V.E.

    1996-01-01

    The proposals on cooperation in the area of thermophysical properties of reactor materials in a broad band of pressure and temperature realized at normal transient and emergency operation activity of nuclear power plants are discussed. 1 fig

  1. The signaling pathway of dopamine D2 receptor (D2R) activation using normal mode analysis (NMA) and the construction of pharmacophore models for D2R ligands.

    Science.gov (United States)

    Salmas, Ramin Ekhteiari; Stein, Matthias; Yurtsever, Mine; Seeman, Philip; Erol, Ismail; Mestanoglu, Mert; Durdagi, Serdar

    2017-07-01

    G-protein-coupled receptors (GPCRs) are targets of more than 30% of marketed drugs. Investigation on the GPCRs may shed light on upcoming drug design studies. In the present study, we performed a combination of receptor- and ligand-based analysis targeting the dopamine D2 receptor (D2R). The signaling pathway of D2R activation and the construction of universal pharmacophore models for D2R ligands were also studied. The key amino acids, which contributed to the regular activation of the D2R, were in detail investigated by means of normal mode analysis (NMA). A derived cross-correlation matrix provided us an understanding of the degree of pair residue correlations. Although negative correlations were not observed in the case of the inactive D2R state, a high degree of correlation appeared between the residues in the active state. NMA results showed that the cytoplasmic side of the TM5 plays a significant role in promoting of residue-residue correlations in the active state of D2R. Tracing motions of the amino acids Arg219, Arg220, Val223, Asn224, Lys226, and Ser228 in the position of the TM5 are found to be critical in signal transduction. Complementing the receptor-based modeling, ligand-based modeling was also performed using known D2R ligands. The top-scored pharmacophore models were found as 5-sited (AADPR.671, AADRR.1398, AAPRR.3900, and ADHRR.2864) hypotheses from PHASE modeling from a pool consisting of more than 100 initial candidates. The constructed models using 38 D2R ligands (in the training set) were validated with 15 additional test set compounds. The resulting model correctly predicted the pIC 50 values of an additional test set compounds as true unknowns.

  2. Mutation of the protein kinase C site in borna disease virus phosphoprotein abrogates viral interference with neuronal signaling and restores normal synaptic activity.

    Directory of Open Access Journals (Sweden)

    Christine M A Prat

    2009-05-01

    Full Text Available Understanding the pathogenesis of infection by neurotropic viruses represents a major challenge and may improve our knowledge of many human neurological diseases for which viruses are thought to play a role. Borna disease virus (BDV represents an attractive model system to analyze the molecular mechanisms whereby a virus can persist in the central nervous system (CNS and lead to altered brain function, in the absence of overt cytolysis or inflammation. Recently, we showed that BDV selectively impairs neuronal plasticity through interfering with protein kinase C (PKC-dependent signaling in neurons. Here, we tested the hypothesis that BDV phosphoprotein (P may serve as a PKC decoy substrate when expressed in neurons, resulting in an interference with PKC-dependent signaling and impaired neuronal activity. By using a recombinant BDV with mutated PKC phosphorylation site on P, we demonstrate the central role of this protein in BDV pathogenesis. We first showed that the kinetics of dissemination of this recombinant virus was strongly delayed, suggesting that phosphorylation of P by PKC is required for optimal viral spread in neurons. Moreover, neurons infected with this mutant virus exhibited a normal pattern of phosphorylation of the PKC endogenous substrates MARCKS and SNAP-25. Finally, activity-dependent modulation of synaptic activity was restored, as assessed by measuring calcium dynamics in response to depolarization and the electrical properties of neuronal networks grown on microelectrode arrays. Therefore, preventing P phosphorylation by PKC abolishes viral interference with neuronal activity in response to stimulation. Our findings illustrate a novel example of viral interference with a differentiated neuronal function, mainly through competition with the PKC signaling pathway. In addition, we provide the first evidence that a viral protein can specifically interfere with stimulus-induced synaptic plasticity in neurons.

  3. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

    Science.gov (United States)

    Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

    2015-08-01

    To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

  4. Impact of physical activity on energy balance, food intake and choice in normal weight and obese children in the setting of acute social stress: a randomized controlled trial.

    Science.gov (United States)

    Horsch, Antje; Wobmann, Marion; Kriemler, Susi; Munsch, Simone; Borloz, Sylvie; Balz, Alexandra; Marques-Vidal, Pedro; Borghini, Ayala; Puder, Jardena J

    2015-02-19

    Psychological stress negatively influences food intake and food choices, thereby contributing to the development of childhood obesity. Physical activity can also moderate eating behavior and influence calorie intake. However, it is unknown if acute physical activity influences food intake and overall energy balance after acute stress exposure in children. We therefore investigated the impact of acute physical activity on overall energy balance (food intake minus energy expenditure), food intake, and choice in the setting of acute social stress in normal weight (NW) and overweight/obese (OW/OB) children as well as the impact of psychological risk factors. After receiving written consent from their parents, 26 NW (BMI foods (6 sweet/6 salty; each of low/high caloric density). Energy balance, food intake/choice and obesity-related psychological risk factors were assessed. Lower overall energy balance (p = 0.019) and a decreased choice of low density salty foods (p foods (104 kcal (34 to 173), p = 0.004) following stress. They scored higher on impulsive behavior (p = 0.005), restrained eating (p stress-induced food intake/choice. Positive parenting tended to be related to lower intake of sweet high density food (-132 kcal, -277 to 2, p = 0.054). In the setting of stress, acute moderate physical activity can address energy balance in children, a benefit which is especially pronounced in the OW/OB. Positive parenting may act as a protective factor preventing stress-induced eating of comfort food. clinicaltrials.gov NCT01693926 The study was a pilot study of a project funded by the Swiss National Science Foundation (CRSII3_147673).

  5. Self-regulation of eating and physical activity is lower in obese female college students as compared to their normal weight counterparts.

    Science.gov (United States)

    Campos-Uscanga, Yolanda; Gutiérrez-Ospina, Gabriel; Morales-Romero, Jaime; Romo-González, Tania

    2017-06-01

    Obesity is characterized, among other features, by overeating, reduced physical activity and an abnormal accumulation of body fat. These features are thought to result, at least in part, from the individual's inability to self-regulate their eating and physical activity behaviors (E&PaB). Self-regulation of the E&PaB is a three-step sequential process: self-observation, self-evaluation and self-reaction. However, it is yet unclear whether deficient self-regulation of E&PaB could predispose, facilitate and/or consolidate obesity. Unraveling this issue is fundamental in order to more precisely define the role of self-regulation of E&PaB in the management of obesity. This research was focused on the question of whether or not self-regulation of E&PaB is related to obesity in female undergraduate students. This population segment seems especially vulnerable to developing obesity since they undergo a significant shift of their E&PaB upon their university enrollment. To address this question, a cross-sectional study with 108 female undergraduate students with normal weight (n = 80) or obesity (n = 28) was performed, in which self-regulation of eating habits and physical activity was measured by two validated scales and a personal data questionnaire. Female undergraduate students displaying lower E&PaB self-reactions were consistently overweight or obese. In addition, a multivariate analysis identified high levels of self-reaction towards eating habits related to a minor presence of overweight issues or obesity. Self-regulation should be an essential component in the strategies for obesity prevention as an integral approach that must include orientation about healthy eating and physical activity behaviors. In addition, further studies on the effect of self-regulation in the treatment of the obesity are needed.

  6. Endotoxin induction of an inhibitor of plasminogen activator in bovine pulmonary artery endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-05

    The effects of bacterial lipopolysaccharide (endotoxin) on the fibrinolytic activity of bovine pulmonary artery endothelial cells were examined. Endotoxin suppressed the net fibrinolytic activity of cell extracts and conditioned media in a dose-dependent manner. The effects of endotoxin required at least 6 h for expression. Cell extracts and conditioned media contained a 44-kDa urokinase-like plasminogen activator. Media also contained multiple plasminogen activators with molecular masses of 65-75 and 80-100 kDa. Plasminogen activators in extracts and media were unchanged by treatment of cells with endotoxin. Diisopropyl fluorophosphate (DFP)-abolished fibrinolytic activity of extracts and conditioned media. DFP-treated samples from endotoxin-treated but not untreated cells inhibited urokinase and tissue plasminogen activator, but not plasmin. Inhibitory activity was lost by incubation at pH 3 or heating to 56/sup 0/C for 10 min. These treatments did not affect inhibitory activity of fetal bovine serum. Incubation of /sup 125/I-urokinase with DFP-treated medium from endotoxin-treated cells produced an inactive complex with an apparent molecular mass of 80-85 kDa.

  7. Diamond Nanoparticles Modify Curcumin Activity: In Vitro Studies on Cancer and Normal Cells and In Ovo Studies on Chicken Embryo Model.

    Directory of Open Access Journals (Sweden)

    Barbara Strojny

    Full Text Available Curcumin has been studied broadly for its wide range of biological activities, including anticancer properties. The major problem with curcumin is its poor bioavailability, which can be improved by the addition of carriers, such as diamond nanoparticles (DN. They are carbon allotropes, and are therefore biocompatible and easily taken up by cells. DN are non-toxic and have antiangiogenic properties with potential applications in cancer therapy. Their large surface makes them promising compounds in a drug delivery system for bioactive agents, as DN create bio-complexes in a fast and simple process of self-organisation. We investigated the cytotoxicity of such bio-complexes against liver cancer cells and normal fibroblasts, revealing that conjugation of curcumin with DN significantly improves its activity. The experiment performed in a chicken embryo model demonstrated that neither curcumin nor DN nor bio-complexes affect embryo development, even though DN can form deposits in tissues. Preliminary results confirmed the applicability of DN as an efficient carrier of curcumin, which improves its performance against cancer cells in vitro, yet is not toxic to an organism, which makes the bio-complex a promising anticancer agent.

  8. Roles of s3 site residues of nattokinase on its activity and substrate specificity.

    Science.gov (United States)

    Wu, Shuming; Feng, Chi; Zhong, Jin; Huan, Liandong

    2007-09-01

    Nattokinase (Subtilisin NAT, NK) is a bacterial serine protease with high fibrinolytic activity. To probe their roles on protease activity and substrate specificity, three residues of S3 site (Gly(100), Ser(101) and Leu(126)) were mutated by site-directed mutagenesis. Kinetics parameters of 20 mutants were measured using tetrapeptides as substrates, and their fibrinolytic activities were determined by fibrin plate method. Results of mutation analysis showed that Gly(100) and Ser(101) had reverse steric and electrostatic effects. Residues with bulky or positively charged side chains at position 100 decreased the substrate binding and catalytic activity drastically, while residues with the same characters at position 101 could obviously enhance protease and fibrinolytic activity of NK. Mutation of Leu(126) might impair the structure of the active cleft and drastically decreased the activity of NK. Kinetics studies of the mutants showed that S3 residues were crucial to keep protease activity while they moderately affected substrate specificity of NK. The present study provided some original insight into the P3-S3 interaction in NK and other subtilisins, as well as showed successful protein engineering cases to improve NK as a potential therapeutic agent.

  9. Reactivity of alpha 1-antitrypsin mutants against proteolytic enzymes of the kallikrein-kinin, complement, and fibrinolytic systems

    NARCIS (Netherlands)

    Patston, P.A.; Roodi, N.; Schifferli, J.A.; Bischoff, Rainer; Courtney, M.; Schapira, M.

    1990-01-01

    Increased extracellular proteolysis because of unregulated activation of blood coagulation, complement, and fibrinolysis is observed in thrombosis, shock, and inflammation. In the present study, we have examined whether the plasma kallikrein-kinin system, the classical pathway of complement, and the

  10. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  11. Incremental health expenditure and lost days of normal activity for individuals with mental disorders: results from the São Paulo Megacity Study.

    Science.gov (United States)

    Chiavegatto Filho, Alexandre Dias Porto; Wang, Yuan-Pang; Campino, Antonio Carlos Coelho; Malik, Ana Maria; Viana, Maria Carmen; Andrade, Laura Helena

    2015-08-05

    With the recent increase in the prevalence of mental disorders in developing countries, there is a growing interest in the study of its consequences. We examined the association of depression, anxiety and any mental disorders with incremental health expenditure, i.e. the linear increase in health expenditure associated with mental disorders, and lost days of normal activity. We analyzed the results from a representative sample survey of residents of the Metropolitan Region of São Paulo (n = 2,920; São Paulo Megacity Mental Health Survey), part of the World Mental Health (WMH) Survey Initiative, coordinated by the World Health Organization and performed in 28 countries. The instrument used for obtaining the individual results, including the assessment of mental disorders, was the WMH version of the Composite International Diagnostic Interview 3.0 (WMH-CIDI 3.0) that generates psychiatric diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Statistical analyses were performed by multilevel generalized least squares (GLS) regression models. Sociodemographic determinants such as income, age, education and marital status were included as controls. Depression, anxiety and any mental disorders were consistently associated with both incremental health expenditure and missing days of normal activity. Depression was associated with an incremental annual expenditure of R$308.28 (95% CI: R$194.05-R$422.50), or US$252.48 in terms of purchasing power parity (PPP). Anxiety and any mental disorders were associated with a lower, but also statistically significant, incremental annual expenditure (R$177.82, 95% CI: 79.68-275.97; and R$180.52, 95% CI: 91.13-269.92, or US$145.64 and US$147.85 in terms of PPP, respectively). Most of the incremental health costs associated with mental disorders came from medications. Depression was independently associated with higher incremental health expenditure than the two most prevalent chronic

  12. Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

    Science.gov (United States)

    Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

    2018-03-20

    The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P thick ILT (P = .021) and thick ILT (A1; P thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  13. Activated Protein C Drives the Hyperfibrinolysis of Acute Traumatic Coagulopathy.

    Science.gov (United States)

    Davenport, Ross A; Guerreiro, Maria; Frith, Daniel; Rourke, Claire; Platton, Sean; Cohen, Mitchell; Pearse, Rupert; Thiemermann, Chris; Brohi, Karim

    2017-01-01

    Major trauma is a leading cause of morbidity and mortality worldwide with hemorrhage accounting for 40% of deaths. Acute traumatic coagulopathy exacerbates bleeding, but controversy remains over the degree to which inhibition of procoagulant pathways (anticoagulation), fibrinogen loss, and fibrinolysis drive the pathologic process. Through a combination of experimental study in a murine model of trauma hemorrhage and human observation, the authors' objective was to determine the predominant pathophysiology of acute traumatic coagulopathy. First, a prospective cohort study of 300 trauma patients admitted to a single level 1 trauma center with blood samples collected on arrival was performed. Second, a murine model of acute traumatic coagulopathy with suppressed protein C activation via genetic mutation of thrombomodulin was used. In both studies, analysis for coagulation screen, activated protein C levels, and rotational thromboelastometry (ROTEM) was performed. In patients with acute traumatic coagulopathy, the authors have demonstrated elevated activated protein C levels with profound fibrinolytic activity and early depletion of fibrinogen. Procoagulant pathways were only minimally inhibited with preservation of capacity to generate thrombin. Compared to factors V and VIII, proteases that do not undergo activated protein C-mediated cleavage were reduced but maintained within normal levels. In transgenic mice with reduced capacity to activate protein C, both fibrinolysis and fibrinogen depletion were significantly attenuated. Other recognized drivers of coagulopathy were associated with less significant perturbations of coagulation. Activated protein C-associated fibrinolysis and fibrinogenolysis, rather than inhibition of procoagulant pathways, predominate in acute traumatic coagulopathy. In combination, these findings suggest a central role for the protein C pathway in acute traumatic coagulopathy and provide new translational opportunities for management of

  14. Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    International Nuclear Information System (INIS)

    Serra, Michael; Chan, Amy; Dubey, Maya; Shea, Thomas B; Gilman, Vladimir

    2008-01-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE−/− mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or −/−, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE−/− cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE−/− cultures, which may be a reflection of the reduced SAM levels in ApoE−/− mice. The differential impact of SAM on ApoE+/+ and −/− neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis. (communication)

  15. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli

    Science.gov (United States)

    Rubin, C.; Xu, G.; Judex, S.

    2001-01-01

    It is generally believed that mechanical signals must be large in order to be anabolic to bone tissue. Recent evidence indicates, however, that extremely low-magnitude (bone formation if induced at a high frequency. We examined the ability of extremely low-magnitude, high-frequency mechanical signals to restore anabolic bone cell activity inhibited by disuse. Adult female rats were randomly assigned to six groups: baseline control, age-matched control, mechanically stimulated for 10 min/day, disuse (hind limb suspension), disuse interrupted by 10 min/day of weight bearing, and disuse interrupted by 10 min/day of mechanical stimulation. After a 28 day protocol, bone formation rates (BFR) in the proximal tibia of mechanically stimulated rats increased compared with age-matched control (+97%). Disuse alone reduced BFR (-92%), a suppression only slightly curbed when disuse was interrupted by 10 min of weight bearing (-61%). In contrast, disuse interrupted by 10 min per day of low-level mechanical intervention normalized BFR to values seen in age-matched controls. This work indicates that this noninvasive, extremely low-level stimulus may provide an effective biomechanical intervention for the bone loss that plagues long-term space flight, bed rest, or immobilization caused by paralysis.

  16. Lipoxin A4 stimulates calcium-activated chloride currents and increases airway surface liquid height in normal and cystic fibrosis airway epithelia.

    LENUS (Irish Health Repository)

    2012-01-01

    Cystic Fibrosis (CF) is a genetic disease characterised by a deficit in epithelial Cl(-) secretion which in the lung leads to airway dehydration and a reduced Airway Surface Liquid (ASL) height. The endogenous lipoxin LXA(4) is a member of the newly identified eicosanoids playing a key role in ending the inflammatory process. Levels of LXA(4) are reported to be decreased in the airways of patients with CF. We have previously shown that in normal human bronchial epithelial cells, LXA(4) produced a rapid and transient increase in intracellular Ca(2+). We have investigated, the effect of LXA(4) on Cl(-) secretion and the functional consequences on ASL generation in bronchial epithelial cells obtained from CF and non-CF patient biopsies and in bronchial epithelial cell lines. We found that LXA(4) stimulated a rapid intracellular Ca(2+) increase in all of the different CF bronchial epithelial cells tested. In non-CF and CF bronchial epithelia, LXA(4) stimulated whole-cell Cl(-) currents which were inhibited by NPPB (calcium-activated Cl(-) channel inhibitor), BAPTA-AM (chelator of intracellular Ca(2+)) but not by CFTRinh-172 (CFTR inhibitor). We found, using confocal imaging, that LXA(4) increased the ASL height in non-CF and in CF airway bronchial epithelia. The LXA(4) effect on ASL height was sensitive to bumetanide, an inhibitor of transepithelial Cl(-) secretion. The LXA(4) stimulation of intracellular Ca(2+), whole-cell Cl(-) currents, conductances and ASL height were inhibited by Boc-2, a specific antagonist of the ALX\\/FPR2 receptor. Our results provide, for the first time, evidence for a novel role of LXA(4) in the stimulation of intracellular Ca(2+) signalling leading to Ca(2+)-activated Cl(-) secretion and enhanced ASL height in non-CF and CF bronchial epithelia.

  17. Three months of strictly controlled daily endurance exercise reduces thrombin generation and fibrinolytic risk markers in younger moderately overweight men

    DEFF Research Database (Denmark)

    Gram, Anne Sofie; Bladbjerg, Else-Marie; Skov, Jane

    2015-01-01

    -PA), plasminogen activator inhibitor type 1 (PAI-1), and von Willebrand factor (vWF). RESULTS: We observed significant within-group decreases in ETP (MOD 7 %; HIGH 6 %) and in t-PA (MOD 22 %; HIGH 21 %) and PAI-1 (MOD 16 %; HIGH 32 %) in both training groups, and no changes in the CON group. At 3 months, between......-group differences were observed for ETP (p = 0.016) and t-PA (p = 0.012) due to significantly lower values in MOD and HIGH compared with CON. Borderline significant between-group differences were observed for PAI-1 (p = 0.082). A significant increase was observed in vWF in HIGH, but with no between...

  18. Normalization: A Preprocessing Stage

    OpenAIRE

    Patro, S. Gopal Krishna; Sahu, Kishore Kumar

    2015-01-01

    As we know that the normalization is a pre-processing stage of any type problem statement. Especially normalization takes important role in the field of soft computing, cloud computing etc. for manipulation of data like scale down or scale up the range of data before it becomes used for further stage. There are so many normalization techniques are there namely Min-Max normalization, Z-score normalization and Decimal scaling normalization. So by referring these normalization techniques we are ...

  19. Variations in the use of emergency PCI for the treatment of re-infarction following intravenous fibrinolytic therapy: impact on outcomes in HERO-2.

    Science.gov (United States)

    Edmond, J J; French, J K; Aylward, P E G; Wong, C K; Stewart, R A H; Williams, B F; De Pasquale, C G; O'connell, R L; Van den Berg, K; Van de Werf, F J; Simes, R J; White, H D

    2007-06-01

    Patients who suffer re-infarction during initial hospitalization for ST-elevation myocardial infarction (STEMI) have decreased survival compared to patients without re-infarction, so treatment of re-infarction may influence survival. To determine whether the utilization of reperfusion therapies varied within 12 h of re-infarction and was associated with 30-day mortality, we studied 552 patients with re-infarction of 17,073 patients with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western Countries, Asia, and Latin America). Patients presenting within 6 h of symptom-onset were randomized to receive either bivalirudin or unfractionated heparin intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6% of bivalirudin and heparin treated patients, respectively (P = 0.004), but treatment assignment did not influence mortality after re-infarction. Patients with re-infarction had a higher 30-day mortality than those without re-infarction (24 vs. 10%; P model). Within 12 h of re-infarction, fibrinolytic therapy was administered to 12.0 and 8.2% underwent percutaneous coronary intervention (PCI); these two treatments were more frequently utilized in patients from Western countries (n = 112), compared to patients from other countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P < 0.001). Mortality was 15% in patients receiving reperfusion therapy for re-infarction and 27% for those with conservative management, hazard ratio (HR) 0.53 (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included adjustment for clinical variables and randomized treatment assignment, 30-day mortality after re-infarction varied by region (highest Latin America 29%, lowest Western countries 15%; P = 0.01). Other independent prognostic factors included age, time from randomization to re-infarction, and Killip class at randomization. The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0

  20. Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist.

    Science.gov (United States)

    Uchida, Masahiko; Ito, Tetsuhide; Nakamura, Taichi; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Takayanagi, Ryoichi; Jensen, Robert T

    2014-07-01

    Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1), in acute/chronic pancreatitis; however, the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues and the effects of CX3CL1 on activated PSCs. CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues was evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated PSCs were examined with real-time polymerase chain reaction, BrdU (5-bromo-2-deoxyuridine) assays, and Western blotting. In normal pancreas, acinar cells expressed CX3CR1 within granule-like formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal, and activated PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1 did not induce inflammatory genes expression in activated PSCs, but induced proliferation. CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis, and the CX3CR1s are activated. CX3CL1 induces proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSC proliferation in pancreatitis where CX3CL1 levels are elevated.

  1. Histone variant H2A.Z antagonizes the positive effect of the transcriptional activator CPC1 to regulate catalase-3 expression under normal and oxidative stress conditions.

    Science.gov (United States)

    Dong, Qing; Wang, Yajun; Qi, Shaohua; Gai, Kexin; He, Qun; Wang, Ying

    2018-05-05

    In eukaryotes, deposition of the histone variant H2A.Z into nucleosomes through the chromatin remodeling complex, SWR1, is a crucial step in modulating gene transcription. Recently, H2A.Z has been shown to control the expression of responsive genes, but the underlying mechanism of how H2A.Z responds to physiological stimuli is not well understood. Here, we reveal that, in Neurospora crassa, H2A.Z is a negative regulator of catalase-3 gene, which is responsible for resistance to oxidative stress. H2A.Z represses cat-3 gene expression through direct incorporation at cat-3 locus in a SWR1 complex dependent pathway. Notably, loss of H2A.Z or SWR1 subunits leads to increased binding of a transcription factor, CPC1, at cat-3 locus. Additionally, introduction of plasmids containing gene encoding H2A.Z or SWR1 complex subunits into wild-type strains decreased CAT-3 expression, indicating that H2A.Z counteracts the positive effect of CPC1 to achieve low level cat-3 expression under non-inductive condition. Furthermore, upon oxidative stress, H2A.Z is rapidly evicted from cat-3 locus for the recruitment of CPC1, resulting in robust and full cat-3 gene expression in response to external stimuli. Collectively, this study strongly demonstrates that H2A.Z antagonizes the function of transcription factor to regulate responsive gene transcription under normal conditions and to poise for gene full activation under oxidative stress. Copyright © 2018. Published by Elsevier Inc.

  2. The Amounts of As, Au, Br, Cu, Fe, Mo, Se and Zn in Normal and Uraemic Human whole Blood. A. Comparison by Means of Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Brune, D; Samsahl, K [AB Atomenergi, Nykoeping (Sweden); Wester, P O [Dept. of Medicine, Karolinska Inst., Serafimerlasarettet, Stockholm (Sweden)

    1964-01-15

    Quantitative determination of the elements As, Au, Br, Cu, Fe, Mo, Se and Zn have been performed in normal and uraemic human whole blood by means of H{sub 2}SO{sub 4} - H-O- digestion, distillation and ion exchange, combined with gamma-spectrometric analysis. The uraemic blood was found to contain about 10 times as much As and twice as much Mo as did the normal blood. As regards Fe, the uraemic blood contained slightly less than the normal blood. For the other elements there were no detectable difference.

  3. Use of a simplified spectrophotometric method for quantitative determination of glucose-6-phosphate dehydrogenase activity in normal children from two day-care centers of the city of São Paulo

    Directory of Open Access Journals (Sweden)

    Roberto Muller

    2003-06-01

    Full Text Available Objective: To evaluate the applicability of a simplified method forquantitative determination of glucose-6-phosphate dehydrogenaseactivity in normal children; to determine the mean, standarddeviation and threshold value under which the enzyme activity isconsidered deficient. Methods: Blood samples were collected from201 children from two day-care centers in the city of São Paulo.The subjects were considered normal based on physicalexamination and laboratory tests. The enzyme activity wasdetermined in red blood cells of normal children using the “TestCombination G-6-PDH®” kit. The following statistical analyses werecarried out: the results were submitted to Student’s t test,Kolmogorov-Smirnov test, lower confidence interval (one-tailedtest and Spearman’s correlation coefficient. Results: The meanhemoglobin value for girls was slightly higher than the mean valuefor boys, but this difference was not statistically significant. Therewas no statistical difference in mean enzyme activities for Caucasianand non-Caucasian children. There was no significant correlation amongenzyme activity levels, red blood cells, hemoglobin levels,hematocrit, reticulocytes, white blood cells and age of patients.The mean enzyme activity for boys was 4.448 U/g Hb, standarddeviation = 1.380 U/g Hb. For girls, the mean enzyme activity was4.531 U/g Hb, standard deviation = 1.386 U/g Hb, and the differencewas not statistically significant. Therefore, the two populationgroups were considered as one single population, presenting amean enzyme activity of 4.490 U/g Hb, standard deviation = 1.380 U/g Hb.Since the distribution curve of enzyme activity values was normal,a lower confidence interval was determined (one-tailed test, witha cutoff point of 2.227 U/g Hb. Conclusion: The method used bySolem proved to be simple, fast, very accurate and useful to detectglucose-6-phosphate dehydrogenase activity and to identifychildren with enzyme deficiency.

  4. Relationship between Inflammation markers, Coagulation Activation and Impaired Insulin Sensitivity in Obese Healthy Women

    International Nuclear Information System (INIS)

    Soliman, S.Et; Shousha, M.A.

    2011-01-01

    Obesity, insulin resistance syndrome, and atherosclerosis are closely linked phenomena, often connected with a chronic low grade inflammatory state and pro thrombotic hypo fibrinolytic condition. This study investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. The study included 36 healthy obese women (body mass index ≥ 30), with normal insulin sensitivity (NIS, n = 18) or impaired insulin sensitivity (IIS, n 18), and 10 non obese women (body mass index < 25).Impaired insulin sensitivity patients had significantly higher levels of high sensitivity C-reactive protein (hs-CRP), transforming growth factor -β1(TGF-β1), plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragments 1 + 2 (F1 + 2) compared with either control subjects or normal insulin sensitivity patients. On the other hand, NIS patients had higher hs-CRP, TGF-β1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-β1, hs-CRP, PAI-1; factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-β1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-β1 and the insulin sensitivity index were independently related to F1 + 2. These results document an in vivo relationship between insulin sensitivity and coagulation activation in obesity. Here we report that obesity is associated with higher TGF-β, PAI-1, prothrombin fragments 1 and 2 (F1 + 2), and activated factor VII (VIIa) plasma levels, and that insulin resistance exacerbates these alterations. The elevated TGF-β1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease

  5. Monomeric adiponectin increases cell viability in porcine aortic endothelial cells cultured in normal and high glucose conditions: Data on kinases activation

    Directory of Open Access Journals (Sweden)

    Elena Grossini

    2016-09-01

    Full Text Available We found that monomeric adiponectin was able to increase cell viability in porcine aortic endothelial cells (PAE cultured both in normal and high glucose condition. Moreover, in normal glucose condition monomeric adiponectin increased p38MAPK, Akt, ERK1/2 and eNOS phosphorylation in a dose- and time-dependent way. Also in high glucose condition monomeric adiponectin increased eNOS and above kinases phosphorylation with similar patterns but at lower extent. For interpretation of the data presented in this article, please see the research article “Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions” (Grossini et al., in press [1].

  6. Epidermal growth factor receptor-induced activato protein 1 activity controls density-dependent growht inhibition in normal rat kidney fibroblasts.

    NARCIS (Netherlands)

    Hornberg, J.J.; Dekker, H.; Peters, P.H.J.; Langerak, P.; Westerhoff, H.V.; Lankelma, J.; Zoelen, E.J.J.

    2006-01-01

    Density-dependent growth inhibition secures tissue homeostasis. Dysfunction of the mechanisms, which regulate this type of growth control is a major cause of neoplasia. In confluent normal rat kidney (NRK) fibroblasts, epidermal growth factor (EGF) receptor levels decline, ultimately rendering these

  7. Normalized modes at selected points without normalization

    Science.gov (United States)

    Kausel, Eduardo

    2018-04-01

    As every textbook on linear algebra demonstrates, the eigenvectors for the general eigenvalue problem | K - λM | = 0 involving two real, symmetric, positive definite matrices K , M satisfy some well-defined orthogonality conditions. Equally well-known is the fact that those eigenvectors can be normalized so that their modal mass μ =ϕT Mϕ is unity: it suffices to divide each unscaled mode by the square root of the modal mass. Thus, the normalization is the result of an explicit calculation applied to the modes after they were obtained by some means. However, we show herein that the normalized modes are not merely convenient forms of scaling, but that they are actually intrinsic properties of the pair of matrices K , M, that is, the matrices already "know" about normalization even before the modes have been obtained. This means that we can obtain individual components of the normalized modes directly from the eigenvalue problem, and without needing to obtain either all of the modes or for that matter, any one complete mode. These results are achieved by means of the residue theorem of operational calculus, a finding that is rather remarkable inasmuch as the residues themselves do not make use of any orthogonality conditions or normalization in the first place. It appears that this obscure property connecting the general eigenvalue problem of modal analysis with the residue theorem of operational calculus may have been overlooked up until now, but which has in turn interesting theoretical implications.Á

  8. Event-related brain potentials, bilateral electrodermal activity and Mangina-Test performance in learning disabled/ADHD pre-adolescents with severe behavioral disorders as compared to age-matched normal controls.

    Science.gov (United States)

    Mangina, C A; Beuzeron-Mangina, J H; Grizenko, N

    2000-07-01

    The most frequently encountered developmental problems of learning disabilities/ADHD often co-exist with severe behavioral disorders. As a direct consequence, this condition opens the way to delinquency, school drop-out, depression, suicide, substance abuse, work absenteeism, and other psycho-social complications. In this paper, we are presenting a selective overview of our previous research and its clinical applications in this field as it relates to our present research data pertaining to the effects of our original Memory Workload Paradigm on the event-related brain potentials in differentiating normal and pathological pre-adolescents (learning disabled/ADHD with concomitant severe behavioral disorders such as oppositional and conduct). In addition, it provides data on the bilateral electrodermal activity during cognitive workload and Mangina-Test performance of pathological and normal pre-adolescents conducted in separate sessions. The results of our present research indicate that a significant memory load effect for the P450 latency (F(3,27)=4.98, PWorkload Paradigm in pre-frontal and frontal regions clearly differentiated normal from pathological pre-adolescents (F(1, 18)=12.21, Presearch findings provide an original and valuable demonstration of an integrative and effective clinical psychophysiological application of central (ERPs), autonomic (bilateral electrodermal activity) and neuro-psychometric aspects (Mangina-Test) which characterize normal and pathological pre-adolescents and underpin the neurophysiological basis of learning disabled/ADHD with severe behavioral disorders as opposed to normal subjects.

  9. THE SPITZER MID-INFRARED ACTIVE GALACTIC NUCLEUS SURVEY. I. OPTICAL AND NEAR-INFRARED SPECTROSCOPY OF OBSCURED CANDIDATES AND NORMAL ACTIVE GALACTIC NUCLEI SELECTED IN THE MID-INFRARED

    Energy Technology Data Exchange (ETDEWEB)

    Lacy, M. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Ridgway, S. E. [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States); Gates, E. L. [UCO/Lick Observatory, P.O. Box 85, Mount Hamilton, CA 95140 (United States); Nielsen, D. M. [Department of Astronomy, University of Wisconsin, 475 N. Charter Street, Madison, WI 53706 (United States); Petric, A. O. [Department of Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Sajina, A. [Department of Physics and Astronomy, Tuffs University, 212 College Avenue, Medford, MA 02155 (United States); Urrutia, T. [Leibniz-Institut für Astrophysik Potsdam, An der Sternwarte 16, D-14482 Potsdam (Germany); Cox Drews, S. [946 Mangrove Avenue 102, Sunnyvale, CA 94086 (United States); Harrison, C. [Department of Astronomy, University of Michigan, Ann Arbor, MI 48109 (United States); Seymour, N. [CSIRO, P.O. Box 76, Epping, NSW 1710 (Australia); Storrie-Lombardi, L. J. [Spitzer Science Center, California Institute of Technology, Pasadena, CA 91125 (United States)

    2013-10-01

    We present the results of a program of optical and near-infrared spectroscopic follow-up of candidate active galactic nuclei (AGNs) selected in the mid-infrared. This survey selects both normal and obscured AGNs closely matched in luminosity across a wide range, from Seyfert galaxies with bolometric luminosities L {sub bol} ∼ 10{sup 10} L {sub ☉} to highly luminous quasars (L {sub bol} ∼ 10{sup 14} L {sub ☉}), all with redshifts ranging from 0 to 4.3. Samples of candidate AGNs were selected with mid-infrared color cuts at several different 24 μm flux density limits to ensure a range of luminosities at a given redshift. The survey consists of 786 candidate AGNs and quasars, of which 672 have spectroscopic redshifts and classifications. Of these, 137 (20%) are type 1 AGNs with blue continua, 294 (44%) are type 2 objects with extinctions A{sub V} ∼> 5 toward their AGNs, 96 (14%) are AGNs with lower extinctions (A{sub V} ∼ 1), and 145 (22%) have redshifts, but no clear signs of AGN activity in their spectra. Of the survey objects 50% have L {sub bol} > 10{sup 12} L {sub ☉}, in the quasar regime. We present composite spectra for type 2 quasars and objects with no signs of AGN activity in their spectra. We also discuss the mid-infrared—emission-line luminosity correlation and present the results of cross correlations with serendipitous X-ray and radio sources. The results show that: (1) obscured objects dominate the overall AGN population, (2) mid-infrared selected AGN candidates exist which lack AGN signatures in their optical spectra but have AGN-like X-ray or radio counterparts, and (3) X-ray and optical classifications of obscured and unobscured AGNs often differ.

  10. Antioxidation, angiotensin converting enzyme inhibition activity, nattokinase, and antihypertension of Bacillus subtilis (natto)-fermented pigeon pea

    OpenAIRE

    Bao-Hong Lee; Yi-Syuan Lai; She-Ching Wu

    2015-01-01

    Because of the high incidence of cardiovascular diseases in Asian countries, traditional fermented foods from Asia have been increasingly investigated for antiatherosclerotic effects. This study investigated the production of nattokinase, a serine fibrinolytic enzyme, in pigeon pea by Bacillus subtilis fermentation. B. subtilis 14714, B. subtilis 14715, B. subtilis 14716, and B. subtilis 14718 were employed to produce nattokinase. The highest nattokinase activity in pigeon pea was obtained us...

  11. Cortical fMRI activation to opponents' body kinematics in sport-related anticipation: expert-novice differences with normal and point-light video.

    Science.gov (United States)

    Wright, M J; Bishop, D T; Jackson, R C; Abernethy, B

    2011-08-18

    Badminton players of varying skill levels viewed normal and point-light video clips of opponents striking the shuttle towards the viewer; their task was to predict in which quadrant of the court the shuttle would land. In a whole-brain fMRI analysis we identified bilateral cortical networks sensitive to the anticipation task relative to control stimuli. This network is more extensive and localised than previously reported. Voxel clusters responding more strongly in experts than novices were associated with all task-sensitive areas, whereas voxels responding more strongly in novices were found outside these areas. Task-sensitive areas for normal and point-light video were very similar, whereas early visual areas responded differentially, indicating the primacy of kinematic information for sport-related anticipation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Discovery of small molecules binding to the normal conformation of prion by combining virtual screening and multiple biological activity evaluation methods

    Science.gov (United States)

    Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun

    2017-12-01

    Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.

  13. Expression of the helix-loop-helix protein inhibitor of DNA binding-1 (ID-1) is activated by all-trans retinoic acid in normal human keratinocytes

    International Nuclear Information System (INIS)

    Villano, C.M.; White, L.A.

    2006-01-01

    The ID (inhibitor of differentiation or DNA binding) helix-loop-helix proteins are important mediators of cellular differentiation and proliferation in a variety of cell types through regulation of gene expression. Overexpression of the ID proteins in normal human keratinocytes results in extension of culture lifespan, indicating that these proteins are important for epidermal differentiation. Our hypothesis is that the ID proteins are targets of the retinoic acid signaling pathway in keratinocytes. Retinoids, vitamin A analogues, are powerful regulators of cell growth and differentiation and are widely used in the prevention and treatment of a variety of cancers in humans. Furthermore, retinoic acid is necessary for the maintenance of epithelial differentiation and demonstrates an inhibitory action on skin carcinogenesis. We examined the effect of all-trans retinoic acid on expression of ID-1, -2, -3, and -4 in normal human keratinocytes and found that exposure of these cells to all-trans retinoic acid causes an increase in both ID-1 and ID-3 gene expression. Furthermore, our data show that this increase is mediated by increased transcription involving several cis-acting elements in the distal portion of the promoter, including a CREB-binding site, an Egr1 element, and an YY1 site. These data demonstrate that the ID proteins are direct targets of the retinoic acid signaling pathway. Given the importance of the ID proteins to epidermal differentiation, these results suggest that IDs may be mediating some of the effects of all-trans retinoic acid in normal human keratinocytes

  14. Normal foot and ankle

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    The foot may be thought of as a bag of bones tied tightly together and functioning as a unit. The bones re expected to maintain their alignment without causing symptomatology to the patient. The author discusses a normal radiograph. The bones must have normal shape and normal alignment. The density of the soft tissues should be normal and there should be no fractures, tumors, or foreign bodies

  15. Purification and characterization of tenerplasminin-1, a serine peptidase inhibitor with antiplasmin activity from the coral snake (Micrurus tener tener) venom.

    Science.gov (United States)

    Vivas, Jeilyn; Ibarra, Carlos; Salazar, Ana M; Neves-Ferreira, Ana G C; Sánchez, Elda E; Perales, Jonás; Rodríguez-Acosta, Alexis; Guerrero, Belsy

    2016-01-01

    A plasmin inhibitor, named tenerplasminin-1 (TP1), was isolated from Micrurus tener tener (Mtt) venom. It showed a molecular mass of 6542Da, similarly to Kunitz-type serine peptidase inhibitors. The amidolytic activity of plasmin (0.5nM) on synthetic substrate S-2251 was inhibited by 91% following the incubation with TP1 (1nM). Aprotinin (2nM) used as the positive control of inhibition, reduced the plasmin amidolytic activity by 71%. Plasmin fibrinolytic activity (0.05nM) was inhibited by 67% following incubation with TP1 (0.1nM). The degradation of fibrinogen chains induced by plasmin, trypsin or elastase was inhibited by TP1 at a 1:2, 1:4 and 1:20 enzyme:inhibitor ratio, respectively. On the other hand, the proteolytic activity of crude Mtt venom on fibrinogen chains, previously attributed to metallopeptidases, was not abolished by TP1. The tPA-clot lysis assay showed that TP1 (0.2nM) acts like aprotinin (0.4nM) inducing a delay in lysis time and lysis rate which may be associated with the inhibition of plasmin generated from the endogenous plasminogen activation. TP1 is the first serine protease plasmin-like inhibitor isolated from Mtt snake venom which has been characterized in relation to its mechanism of action, formation of a plasmin:TP1 complex and therapeutic potential as anti-fibrinolytic agent, a biological characteristic of great interest in the field of biomedical research. They could be used to regulate the fibrinolytic system in pathologies such as metastatic cancer, parasitic infections, hemophilia and other hemorrhagic syndromes, in which an intense fibrinolytic activity is observed. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

    International Nuclear Information System (INIS)

    Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A.

    1990-01-01

    To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01)

  17. Does plasmin have anticoagulant activity?

    Directory of Open Access Journals (Sweden)

    Jane Hoover-Plow

    2010-03-01

    Full Text Available Jane Hoover-PlowJoseph J Jacobs Center for Thrombosis and Vascular Biology, Departments of Cardiovascular Medicine and Molecular Cardiology, Lerner Research Institute Cleveland Clinic, Ohio, USAAbstract: The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy.Keywords: thrombosis, anticoagulant, cardiovascular disease, plasminogen’s protease, blood

  18. Caracterização isozimática e atividade de peroxidase em folhas de plantas hiperídrica, intermediária e normal de Bidens pilosa L. mantidas in vitro Isoezymatic characterization and peroxidase activity in leaves of hyperhydric, intermediary and normal plants of Bidens pilosa L. grown in vitro

    Directory of Open Access Journals (Sweden)

    José Emílio Zanzirolani de Oliveira

    2008-02-01

    Full Text Available Foram caracterizadas as plantas: hiperídrica, intermediária e normal de um clone de Bidens pilosa mantido em cultivo in vitro por meio de isozimas e da atividade de peroxidase. Empregando-se a eletroforese em géis de amido a 12%, testou-se seis isozimas, sendo detectado polimorfismo em peroxidase e fosfatase ácida, permitindo caracterizar cada tipo de planta. Não houve polimorfismo em fosfogluco isomerase, fosfoglucomutase, glutamato oxaloacetato transaminase e malato desidrogenase. A atividade da peroxidase foi maior nas plantas hiperídricas e intermediárias. Conclui-se que a variabilidade enzimática tem potencial como marcador de hiperidricidade em plantas mantidas in vitro.Activity of peroxidase (EC 1.11.1.7 and isozymes analysis of a Bidens pilosa clone maintained in vitro culture were characterized in hyperhydric, intermediary and normal plants. Electrophorese in starch gels (12% of six isozymes systems was tested, polymorphisms in peroxidase and acid phosphatase (EC 3.1.3.2 were detected. There was absence of polymorphism in phosphoglucoisomerase (EC 5.3.1.9, phosphoglucomutase (EC 5.4.2.2, glutamate oxaloacetate transaminase (EC 2.6.1.1 and malate dehydrogenase (EC 1.1.1.37. Comparing the activity of peroxidase enzyme, it was higher in hyperhydric and intermediary plants in relation to normal ones. Enzymatic variability is a potential tool as hyperhydricity marker in plants grown in vitro.

  19. Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up.

    Science.gov (United States)

    Berg, Jan; Kottwitz, Jan; Baltensperger, Nora; Kissel, Christine K; Lovrinovic, Marina; Mehra, Tarun; Scherff, Frank; Schmied, Christian; Templin, Christian; Lüscher, Thomas F; Heidecker, Bettina; Manka, Robert

    2017-11-01

    There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months. LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes. This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis. © 2017 American Heart Association, Inc.

  20. Hair-Normalized Cortisol Waking Response as a Novel Biomarker of Hypothalamic-Pituitary-Adrenal Axis Activity following Acute Trauma: A Proof-of-Concept Study with Pilot Results

    Directory of Open Access Journals (Sweden)

    David M. Walton

    2013-01-01

    Full Text Available The mechanisms underlying the development of persistent posttraumatic pain and disability remain elusive. Recent evidence suggests that disordered stress-system pathway (hypothalamic-pituitary-adrenal axis activity may be responsible for the genesis and maintenance of long-term sensory and emotional problems. However, confidence in current evidence is limited by the necessarily retrospective collection of data. Hair cortisol can serve as a calendar of HPA axis activity going back several months prior to injury. The purposes of this pilot study were to determine the feasibility of using hair cortisol and hair-normalized salivary cortisol as biomarkers of distress following traumatic injuries of whiplash or distal radius fracture. Ten subjects provided complete data within 3 weeks of injury. Hair cortisol, cortisol waking response (CWR, and mean daily cortisol (MDC were captured at inception, as were self-report indicators of pain, disability, and pain catastrophizing. Pain and disability were also captured 3 months after injury. Results indicate that cortisol waking response may be a useful biomarker of current distress as measured using the pain catastrophizing scale, especially when normalized to 3-month hair cortisol (r=0.77 raw, 0.93 normalized. Hair-normalized CWR may also have predictive capacity, correlating with 3-month self-reported disability at r=0.70. While promising, the results must be viewed in light of the small sample.

  1. Pharmacokinetic Comparison of Seven Major Bio-Active Components in Normal and Blood Stasis Rats after Oral Administration of Herb Pair Danggui-Honghua by UPLC-TQ/MS

    Directory of Open Access Journals (Sweden)

    Yi Jin

    2017-10-01

    Full Text Available The compatibility between Danggui (Angelicae Sinensis Radix and Honghua (Carthami Flos is a known herb pair, which could activate blood circulation and dissipate blood stasis effects. In this paper, we quantified seven main bio-active components (hydroxysafflor yellow A, caffeic acid, p-coumaric acid, kaempferol-3-O-rutinoside, ferulic acid, 3-n-butylphthalide, and ligustilide in plasma samples in vivo by UPLC-TQ/MS method and investigatedwhether the pharmacokinetic (PK behaviors of the seven components could be altered in blood stasis rats after oral administration of the Gui-Hong extracts. It was found that the Cmax and AUC0-t of these components in blood stasis rats had increasing tendency compared with normal rats. Most components in model and normal rats had significant difference in some pharmacokinetic parameters, which indicated that the metabolism enzymes and transporters involved in the metabolism and disposition of these bio-active componentsmay bealtered in blood stasis rats. This study was the first report about the pharmacokinetic investigation between normal and blood stasis rats after oral administrationof Gui-Hong extracts, and these results are important and valuable for better clinical applications of Gui-Hong herb pair and relatedTCM formulae.

  2. Platelets retain high levels of active plasminogen activator inhibitor 1.

    Directory of Open Access Journals (Sweden)

    Helén Brogren

    Full Text Available The vascular fibrinolytic system is crucial for spontaneous lysis of blood clots. Plasminogen activator inhibitor 1 (PAI-1, the principal inhibitor of the key fibrinolytic enzyme tissue-type plasminogen activator (tPA, is present in platelets at high concentrations. However, the majority of PAI-1 stored in platelets has been considered to be inactive. Our recent finding (Brogren H, et al. Blood 2004 that PAI-1 de novo synthesized in platelets remained active for over 24 h, suggested that PAI-1 stored in the α-granules might be active to a larger extent than previously reported. To re-evaluate this issue, we performed experiments where the fraction of active PAI-1 was estimated by analyzing the tPA-PAI-1 complex formation. In these experiments platelets were lysed with Triton X-100 in the presence of serial dilutions of tPA and subsequently the tPA-PAI-1 complex was evaluated by Western blot. Also, using a non-immunologic assay, tPA was labeled with (125I, and (125I-tPA and (125I-tPA-PAI-1 was quantified by scintigraphy. Interestingly, both methods demonstrated that the majority (>50% of platelet PAI-1 is active. Further analyses suggested that pre-analytical procedures used in previous studies (sonication or freezing/thawing may have substantially reduced the activity of platelet PAI-1, which has lead to an underestimation of the proportion of active PAI-1. Our in vitro results are more compatible with the role of PAI-1 in clot stabilization as demonstrated in physiological and pathophysiological studies.

  3. Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers.

    Science.gov (United States)

    Markowitz, John S; Donovan, Jennifer L; Devane, C Lindsay; Taylor, Robin M; Ruan, Ying; Wang, Jun-Sheng; Chavin, Kenneth D

    2003-12-01

    Saw palmetto (Serenoa repens) is the most commonly used herbal preparation in the treatment of benign prostatic hyperplasia. The objective of this study was to determine whether a characterized saw palmetto product affects the activity of cytochrome P450 (CYP) 2D6 or 3A4 in healthy volunteers (6 men and 6 women). The probe substrates dextromethorphan (CYP2D6 activity) and alprazolam (CYP3A4 activity) were administered orally at baseline and again after exposure to saw palmetto (320-mg capsule once daily) for 14 days. Dextromethorphan metabolic ratios and alprazolam pharmacokinetics were determined at baseline and after saw palmetto treatment. The mean ratio of dextromethorphan to its metabolite was 0.038 +/- 0.044 at baseline and 0.048 +/- 0.080 after 14 days of saw palmetto administration (P =.704, not significant [NS]), indicating a lack of effect on CYP2D6 activity. The area under the plasma alprazolam concentration versus time curve was 476 +/- 178 h. ng. mL(-1) at baseline and 479 +/- 125 h. ng. mL(-1) after saw palmetto treatment (P =.923, NS), indicating a lack of effect on CYP3A4 activity. The elimination half-life of alprazolam was 11.4 +/- 3.1 hours at baseline and 11.6 +/- 2.7 hours after saw palmetto treatment (P =.770, NS), also indicating a lack of effect on CYP3A4 activity. Our results indicate that extracts of saw palmetto at generally recommended doses are unlikely to alter the disposition of coadministered medications primarily dependent on the CYP2D6 or CYP3A4 pathways for elimination. These conclusions must be weighed in the context of the study's limited assessments and regarded as only the initial investigation into the drug interaction potential of saw palmetto.

  4. Baby Poop: What's Normal?

    Science.gov (United States)

    ... I'm breast-feeding my newborn and her bowel movements are yellow and mushy. Is this normal for baby poop? Answers from Jay L. Hoecker, M.D. Yellow, mushy bowel movements are perfectly normal for breast-fed babies. Still, ...

  5. The effects of rose hip (Rosa canina) on plasma antioxidative activity and C-reactive protein in patients with rheumatoid arthritis and normal controls: A prospective cohort study

    DEFF Research Database (Denmark)

    Kirkeskov, Bente; Christensen, Robin; Bügel, Susanne Gjedsted

    2011-01-01

    OBJECTIVES: Rose hip (Rosa canina) has been used as an herbal remedy against a wide range of ailments including inflammatory disorders. The anti-inflammatory and antioxidant properties of rose hips have been evaluated in vitro and active constituents have been isolated. Rose hip contains antioxid......OBJECTIVES: Rose hip (Rosa canina) has been used as an herbal remedy against a wide range of ailments including inflammatory disorders. The anti-inflammatory and antioxidant properties of rose hips have been evaluated in vitro and active constituents have been isolated. Rose hip contains...

  6. Visual Memories Bypass Normalization.

    Science.gov (United States)

    Bloem, Ilona M; Watanabe, Yurika L; Kibbe, Melissa M; Ling, Sam

    2018-05-01

    How distinct are visual memory representations from visual perception? Although evidence suggests that briefly remembered stimuli are represented within early visual cortices, the degree to which these memory traces resemble true visual representations remains something of a mystery. Here, we tested whether both visual memory and perception succumb to a seemingly ubiquitous neural computation: normalization. Observers were asked to remember the contrast of visual stimuli, which were pitted against each other to promote normalization either in perception or in visual memory. Our results revealed robust normalization between visual representations in perception, yet no signature of normalization occurring between working memory stores-neither between representations in memory nor between memory representations and visual inputs. These results provide unique insight into the nature of visual memory representations, illustrating that visual memory representations follow a different set of computational rules, bypassing normalization, a canonical visual computation.

  7. Validation of normalized pulse volume in the outer ear as a simple measure of sympathetic activity using warm and cold pressor tests: towards applications in ambulatory monitoring

    International Nuclear Information System (INIS)

    Lee, Jihyoung; Matsumura, Kenta; Yamakoshi, Takehiro; Tanaka, Naoto; Yamakoshi, Ken-ichi; Rolfe, Peter; Kim, Kyungho

    2013-01-01

    Normalized pulse volume (NPV) derived from the ear has the potential to be a practical index for monitoring daily life stress. However, ear NPV has not yet been validated. Therefore, we compared NPV derived from an index finger using transmission photoplethysmography as a reference, with NPV derived from a middle finger and four sites of the ear using reflection photoplethysmography during baseline and while performing cold and warm water immersion in ten young and six middle-aged subjects. The results showed that logarithmically-transformed NPV (lnNPV) during cold water immersion as compared with baseline values was significantly lower, only at the index finger, the middle finger and the bottom of the ear-canal. Furthermore, lnNPV reactivities (ΔlnNPV; the difference between baseline and test values) from an index finger were significantly related to ΔlnNPV from the middle finger and the bottom of the ear-canal (young: r = 0.90 and 0.62, middle-aged: r = 0.80 and 0.58, respectively). In conclusion, these findings show that reflection and transmission photoplethysmography are comparable methods to derive NPV in accordance with our theoretical prediction. NPV derived from the bottom of the ear-canal is a valid approach, which could be useful for evaluating daily life stress. (paper)

  8. TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways.

    Science.gov (United States)

    Tacheau, Charlotte; Fontaine, Juliette; Loy, Jennifer; Mauviel, Alain; Verrecchia, Franck

    2008-12-01

    One of the shared physiological roles between TGF-beta and connexin family members is to inhibit epithelial cell cycle progression and consequently, to provide protection against malignant transformation. Herein, we demonstrated that TGF-beta1 induces the expression of connexin43 (Cx43) in normal murine mammary gland (NMuMG) cell lines at the protein and mRNA levels, and transcriptionally. Using overexpression of a truncated dominant-negative form of Cx43, we determined that the modulation of gap junctional communication by TGF-beta1 plays a key role in the control of NMuMG cells proliferation by TGF-beta1. In addition, using overexpression of truncated dominant-negative forms of either Smad2 or Smad3, and MDA-MB-468 human breast carcinoma cells deficient for Smad4, we determined that the Smad cascade is not implicated in TGF-beta1 effect on Cx43 expression. Using specific pharmacologic inhibitors for JNK, ERK, p38, and PI3K/AKT signaling pathways, we demonstrated the cooperative role of p38 and PI3K/AKT signaling in TGF-beta1-induced Cx43 expression and gap junctional communication. Furthermore, transfection of a c-jun antisense expression vector significantly prevented TGF-beta1-induced Cx43 gene expression demonstrating the involvement of c-Jun/AP-1 pathway together with p38 and PI3K/AKT pathways in mediating TGF-beta1-induced Cx43 gene expression.

  9. The membrane attack complex of complement contributes to plasmin-induced synthesis of platelet-activating factor by endothelial cells and neutrophils.

    Science.gov (United States)

    Lupia, Enrico; Del Sorbo, Lorenzo; Bergerone, Serena; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

    2003-08-01

    Thrombolytic agents, used to restore blood flow to ischaemic tissues, activate several enzymatic systems with pro-inflammatory effects, thus potentially contributing to the pathogenesis of ischaemia-reperfusion injury. Platelet-activating factor (PAF), a phospholipid mediator of inflammation, has been implicated in the pathogenesis of this process. We previously showed that the infusion of streptokinase (SK) induces the intravascular release of PAF in patients with acute myocardial infarction (AMI), and that cultured human endothelial cells (EC) synthesized PAF in response to SK and plasmin (PLN). In the present study, we investigated the role of the membrane attack complex (MAC) of complement in the PLN-induced synthesis of PAF. In vivo, we showed a correlation between the levels of soluble terminal complement components (sC5b-9) and the concentrations of PAF detected in blood of patients with AMI infused with SK. In vitro both EC and polymorphonuclear neutrophils (PMN), incubated in the presence of PLN and normal human serum, showed an intense staining for the MAC neoepitope, while no staining was detected when they were incubated with PLN in the presence of heat-inactivated normal human serum. Moreover, the insertion of MAC on EC and PMN plasmamembrane elicited the synthesis of PAF. In conclusion, our results elucidate the mechanisms involved in PAF production during the activation of the fibrinolytic system, showing a role for complement products in this setting. The release of PAF may increase the inflammatory response, thus limiting the beneficial effects of thrombolytic therapy. Moreover, it may have a pathogenic role in other pathological conditions, such as transplant rejection, tumoral angiogenesis, and septic shock, where fibrinolysis is activated.

  10. Role of thyroid hormones in the normal and glucocorticosteroid hormone-induced evolution of carbamoyl-phosphate synthase (ammonia) activity in axolotl liver

    NARCIS (Netherlands)

    Lamers, W. H.; Vink, C.; Charles, R.

    1978-01-01

    1. In axolotl liver, the activity of carbamoyl-phosphate synthase (ammonia), expressed per mg liver protein, decreases to a minimum at 5 months of age, then increases to a maximum at 8 months of age which is followed by a decrease again. The initial decrease between 3 and 5 months of age appears to

  11. The effects of rose hip (Rosa canina) on plasma antioxidative activity and C-reactive protein in patients with rheumatoid arthritis and normal controls

    DEFF Research Database (Denmark)

    Nielsen, Bente Kirkeskov; Christensen, Robin; Bügel, Susanne Gjedsted

    2011-01-01

    OBJECTIVES: Rose hip (Rosa canina) has been used as an herbal remedy against a wide range of ailments including inflammatory disorders. The anti-inflammatory and antioxidant properties of rose hips have been evaluated in vitro and active constituents have been isolated. Rose hip contains antioxid...

  12. Esterase activity in the guinea pig thyroid under normal and pathological conditions (vitamin A deficiency) with special regard to cyst-like structures

    DEFF Research Database (Denmark)

    Kirkeby, S

    1977-01-01

    By use of different activators and inhibitors, TOCP(tri-o-cresyl phosphate), PCMB (parachloromercury benzoate), NiCl2, Pb(NO3)2, HgCl2, Hg(NO3)2, eserine and sodium taurocholate, it is shown that the esterase in the cyst cells and in group I cells of the guinea pig thyroid probably are A...

  13. Role of phospholipase C in Dictyostelium : Formation of inositol 1,4,5-trisphosphate and normal development in cells lacking phospholipase C activity

    NARCIS (Netherlands)

    Drayer, A. Lyndsay; Kaay, Jeroen van der; Mayr, Georg W.; Haastert, Peter J.M. van

    1994-01-01

    The micro-organism Dictyostelium uses extracellular cAMP to induce chemotaxis and cell differentiation. Signals are transduced via surface receptors, which activate G proteins, to effector enzymes. The deduced protein sequence of Dictyostelium discoideum phosphabidylinositol-specific phospholipase C

  14. THE EFFECT OF NIMODIPINE ON COCHLEAR POTENTIALS AND NA+/K+-ATPASE ACTIVITY IN NORMAL AND HYDROPIC COCHLEAS OF THE ALBINO GUINEA-PIG

    NARCIS (Netherlands)

    VANBENTHEM, PPG; KLIS, SFL; ALBERS, FWJ; DEWILDT, DJ; VELDMAN, JE; HUIZING, EH; SMOORENBURG, GF

    1994-01-01

    In experimental endolymphatic hydrops (EEH) a decrease in the endocochlear potential (EP) has been reported and is thought to be due to decreased activity of the enzyme Na+/K+-ATPase in the stria vascularis. By stimulating Na+/K+-ATPase, the EP, and thereby cochlear function as a whole, might be

  15. Metabolic in Vivo Labeling Highlights Differences of Metabolically Active Microbes from the Mucosal Gastrointestinal Microbiome between High-Fat and Normal Chow Diet

    NARCIS (Netherlands)

    Oberbach, Andreas; Haange, Sven Bastiaan; Schlichting, Nadine; Heinrich, Marco; Lehmann, Stefanie; Till, Holger; Hugenholtz, Floor; Kullnick, Yvonne; Smidt, Hauke; Frank, Karin; Seifert, Jana; Jehmlich, Nico; Bergen, Von Martin

    2017-01-01

    The gastrointestinal microbiota in the gut interacts metabolically and immunologically with the host tissue in the contact zone of the mucus layer. For understanding the details of these interactions and especially their dynamics it is crucial to identify the metabolically active subset of the

  16. Sensory-specific appetite is affected by actively smelled food odors and remains stable over time in normal-wight women

    NARCIS (Netherlands)

    Ramaekers, M.G.; Boesveldt, S.; Lakemond, C.M.M.; Boekel, van M.A.J.S.; Luning, P.A.

    2014-01-01

    Understanding overconsumption starts with knowledge of how separate factors influence our eating behavior. Food cues such as food odors are known for their effect on general appetite and sensory-specific appetite (SSA). Active sniffing rather than passive exposure may induce satiation over time. The

  17. Effect of a mixture of pyridostigmine and atropine on forced expiratory volume (FEV1), and serum cholinesterase activity in normal subjects

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B F; Gefke, Kaj; Mosbech, H

    1985-01-01

    injection with a decrease to 27 +/- 5% (mean +/- SEM) of the original activity. Forced expiratory volume in the first 1s (FEV1) was measured at fixed time intervals for 90 min. No decrease in FEV1 was observed; on the contrary, there was a small increase. We conclude that atropine effectively antagonizes...

  18. Effects of high doses of enalapril and benazepril on the pharmacologically activated renin-angiotensin-aldosterone system in clinically normal dogs.

    Science.gov (United States)

    Ames, Marisa K; Atkins, Clarke E; Lee, Seunggon; Lantis, Andrea C; zumBrunnen, James R

    2015-12-01

    To determine whether high doses of enalapril and benazepril would be more effective than standard doses of these drugs in suppressing the furosemide-activated renin-angiotensin-aldosterone system (RAAS). 6 healthy Beagles. 2 experiments were conducted; each lasted 10 days, separated by a 2-week washout period. In experiment 1, all dogs received furosemide (2 mg/kg, PO, q 12 h) and enalapril (1 mg/kg, PO, q 12 h) for 8 days (days 0 through 7). In experiment 2, dogs received furosemide (2 mg/kg, PO, q 12 h) and benazepril (1 mg/kg, PO, q 12 h) for 8 days. Effects on the RAAS were determined by assessing serum angiotensin-converting enzyme (ACE) activity on days -1, 3, and 7; serum aldosterone concentration on days -2, -1, 1, 3, and 7; and the urinary aldosterone-creatinine ratio (UAldo:C) in urine collected in the morning and evening of days -2, -1, 1, 3, and 7. High doses of enalapril and benazepril caused significant reductions in serum ACE activity on all days but were not more effective than standard doses used in other studies. Mean UAldo:C remained significantly higher on days 2 through 7, compared with baseline values. Serum aldosterone concentration also increased after drug administration, which mirrored changes in the UAldo:C. In this study, administration of high doses of enalapril and benazepril significantly inhibited ACE activity, yet did not prevent increases in mean urine and serum aldosterone concentrations resulting from furosemide activation of RAAS. This suggested that aldosterone breakthrough from ACE inhibition was a dose-independent effect of ACE inhibitors.

  19. Comparative tissue distribution profiles of five major bio-active components in normal and blood deficiency rats after oral administration of Danggui Buxue Decoction by UPLC-TQ/MS.

    Science.gov (United States)

    Shi, Xuqin; Tang, Yuping; Zhu, Huaxu; Li, Weixia; Li, Zhenhao; Li, Wei; Duan, Jin-ao

    2014-01-01

    Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) were frequently combined and used in China as herbal pair called as Danggui Buxue Decoction (DBD) for treatment of blood deficiency syndrome, such as women's ailments. This study is to investigate the tissue distribution profiles of five major bio-active constituents (ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV) in DBD after oral administration of DBD in blood deficiency rats, and to compare the difference between normal and blood deficiency rats. The blood deficiency rats were induced by bleeding from orbit at the dosages of 5.0mLkg(-1) every day, and the experimental period was 12 days. At the finally day of experimental period, both normal and blood deficiency rats were orally administrated with DBD, and then the tissues samples were collected at different time points. Ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV in different tissues were detected simultaneously by UPLC-TQ/MS, and the histograms were drawn. The results showed that the overall trend was CLiver>CKidney>CHeart>CSpleen>CLung, CC-30min>CM-30min>CM-60min>CC-5min>CM-5min>CC-60min>CM-240min>CC-240min. The contents of the detected compounds in liver were more than that in other tissues no matter in normal or blood deficiency rats. Compared to normal rats, partial contents of the compounds in blood deficiency rats' tissues at different time points had significant difference (Pdistribution investigation in blood deficiency animals which is conducted by bleeding. And the results demonstrated that the five DBD components in normal and blood deficiency rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in blood deficiency animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Screening for MPL mutations in essential thrombocythemia and primary myelofibrosis: normal Mpl expression and absence of constitutive STAT3 and STAT5 activation in MPLW515L-positive platelets.

    Science.gov (United States)

    Glembotsky, Ana C; Korin, Laura; Lev, Paola R; Chazarreta, Carlos D; Marta, Rosana F; Molinas, Felisa C; Heller, Paula G

    2010-05-01

    To evaluate the frequency of MPL W515L, W515K and S505N mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) and to determine whether MPLW515L leads to impaired Mpl expression, constitutive STAT3 and STAT5 activation and enhanced response to thrombopoietin (TPO). Mutation detection was performed by allele-specific PCR and sequencing. Platelet Mpl expression was evaluated by flow cytometry, immunoblotting and real-time RT-PCR. Activation of STAT3 and STAT5 before and after stimulation with increasing concentrations of TPO was studied by immunoblotting. Plasma TPO was measured by ELISA. MPLW515L was detected in 1 of 100 patients with ET and 1 of 11 with PMF. Platelets from the PMF patient showed 100% mutant allele, which was Mpl surface and total protein expression were normal, and TPO levels were mildly increased in the MPLW515L-positive ET patient, while MPL transcripts did not differ from controls in both MPLW515L-positive patients. Constitutive STAT3 and STAT5 phosphorylation was absent and dose response to TPO-induced phosphorylation was not enhanced. The low frequency of MPL mutations in this cohort is in agreement with previous studies. The finding of normal Mpl levels in MPLW515L-positive platelets indicates this mutation does not lead to dysregulated Mpl expression, as frequently shown for myeloproliferative neoplasms. The lack of spontaneous STAT3 and STAT5 activation and the normal response to TPO is unexpected as MPLW515L leads to constitutive receptor activation and hypersensitivity to TPO in experimental models.

  1. Plasminogen activator inhibitor-1 in the evolution of stroke

    Directory of Open Access Journals (Sweden)

    Jovanović Zagorka B.

    2004-01-01

    Full Text Available Fibrinolytic activity in the acute stroke was examined by monitoring the level of plasminogen activator inhibitor-1 (PAI-1, as one of the indicators of fibrinolytic activity. Given the role of PAI-1 in the processes of atherogenesis and thrombogenesis, plasma PAI-1 level was measured in 59 patients (up to 50 years of age with atherothrombotic stroke (verified by computed tomography scanning or magnetic resonance imaging of brain in the period from 12 to 24 hours (I analysis and 30 days after the onset of stroke (II analysis; then, it was correlated with plasma PAI-1 level in the control group (57 healthy subjects, which was 2.86±0.70 U/ml. It was found that PAI-1 level was significantly higher in the acute stroke (I analysis: PAI-1 =4.10±1.40 U/ml, p<0.001; II analysis: PAI-1 =3.64+0.90 U/ml, p<0.001, while fibrinolytic activity was lower, especially on the first day from the stroke that was not completely increased even after 30 days. There was no difference in PAI-1 levels between the subgroups of patients with infarction and lacunar cerebral ischemia (p>0.05, as well as between females and males (p>0.05. Along with significantly increased fibrinogen level (4.65±1 g/l, in the controls - 2.83±0.64 g/l, p<0.001, significantly higher triglycerides (2.04±0.76 mmol/l, in the controls - 1.38+0.54 mmol/l, p<0.001 and lipoproteins(a (0.405±0.29 g/l, in the controls -0.172±0.14 g/l, p<0.001 were found, correlating with higher plasma PAI-1 level in these patients. The increased plasma level of PAI-1 pointed to possibility of decreased fibrinolytic activity in pathogenesis of ischemie stroke, as well as, risk of reinsult, which had been the greatest after the onset of stroke and declined gradually within several weeks.

  2. The effects of rose hip (Rosa canina) on plasma antioxidative activity and C-reactive protein in patients with rheumatoid arthritis and normal controls: a prospective cohort study.

    Science.gov (United States)

    Kirkeskov, Bente; Christensen, Robin; Bügel, Susanne; Bliddal, Henning; Danneskiold-Samsøe, Bente; Christensen, Lars Porskjær; Andersen, Jens Rikardt

    2011-08-15

    Rose hip (Rosa canina) has been used as an herbal remedy against a wide range of ailments including inflammatory disorders. The anti-inflammatory and antioxidant properties of rose hips have been evaluated in vitro and active constituents have been isolated. Rose hip contains antioxidant nutrients and an anti-inflammatory galactolipid. Rheumatoid arthritis (RA) is an inflammatory disease where activated cells release reactive oxygen substances. Thus it could be relevant to investigate if rose hip had an anti-inflammatory and/or antioxidant effect in this situation. In this open case-control study 20 female patients with RA and 10 female controls were given 10.5 g rose hip powder daily (Litozin®) for 28 days. Blood samples were analysed at baseline and follow-up for the capacity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase and the inflammatory marker C-reactive protein (CRP). The participants kept a food diary for the first 3 days and the last 3 days of the intervention period. The RA-patients completed The Stanford Health Assessment Questionnaire at baseline and follow-up. CRP-concentrations of both patients and healthy controls did not change. Nor was any effect found on the activity of antioxidant enzymes. There was no difference in food intake at baseline, but in the last week the RA-group reduced their energy intake. 10.5 g Litozin® in 28 days had neither effect on clinical symptoms or laboratory measurements in patients with RA or healthy controls. This is in contrast to previous intervention studies with rose hip powder that found a reduction in the concentration of CRP. The results of the present study indicate that a daily amount of approximately 10 g rose hip powder for one month has no anti-inflammatory and/or antioxidant effect. Copyright © 2011 Elsevier GmbH. All rights reserved.

  3. High sensitivity but normal DNA-repair activity after UV irradiation in Epstein-Barr virus-transformed lymphoblastoid cell lines from Chediak-Higashi syndrome

    International Nuclear Information System (INIS)

    Tanaka, H.; Orii, T.

    1980-01-01

    We established lymphoblastoid cell lines from 2 children with Chediak-Higashi syndrome (CHS), 2 xeroderma pigmentosum (XP) patients and control donors after transformation of peripheral lymphocytes by Epstein-Barr virus (EBV). We used these lymphoblastoid cell lines to investigate repair activity after ultraviolet irradiation. Cell survival of both CHS lymphoblastoid cell lines after irradiation by UV and treatment by 4-nitroquinoline 1-oxide (4NQO) fell between those of the XP and control cells lines. Unscheduled DNA synthesis of CHS cells after UV irradiation occured at rates similar to those of control cells. (orig.)

  4. Activation of lateral geniculate nucleus and primary visual cortex as detected by functional magnetic resonance imaging in normal subjects and in patients with visual disturbance

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Atsushi [Niigata Univ. (Japan). Graduate School of Medical and Dental Sciences

    2002-12-01

    Functional magnetic resonance imaging (fMRI) during visual stimulation can detect regional cerebral blood flow changes that reflect neural activity in the lateral geniculate nucleus and primary visual cortex, which are major relay points in the human afferent visual system. FMRI has been used in the clinical evaluation of visual disorders such as homonymous hemianopia and unilateral eye diseases (optic neuritis, amblyopia, and so on). Future development in the data acquisition and data analysis may facilitate the use of fMRI for the management of patients with visual deficits and understanding of the visual disorders. (author)

  5. Activation of lateral geniculate nucleus and primary visual cortex as detected by functional magnetic resonance imaging in normal subjects and in patients with visual disturbance

    International Nuclear Information System (INIS)

    Miki, Atsushi

    2002-01-01

    Functional magnetic resonance imaging (fMRI) during visual stimulation can detect regional cerebral blood flow changes that reflect neural activity in the lateral geniculate nucleus and primary visual cortex, which are major relay points in the human afferent visual system. FMRI has been used in the clinical evaluation of visual disorders such as homonymous hemianopia and unilateral eye diseases (optic neuritis, amblyopia, and so on). Future development in the data acquisition and data analysis may facilitate the use of fMRI for the management of patients with visual deficits and understanding of the visual disorders. (author)

  6. Normal Pressure Hydrocephalus

    Science.gov (United States)

    ... improves the chance of a good recovery. Without treatment, symptoms may worsen and cause death. What research is being done? The NINDS conducts and supports research on neurological disorders, including normal pressure hydrocephalus. Research on disorders such ...

  7. Normality in Analytical Psychology

    Science.gov (United States)

    Myers, Steve

    2013-01-01

    Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity. PMID:25379262

  8. Normal pressure hydrocephalus

    Science.gov (United States)

    Hydrocephalus - occult; Hydrocephalus - idiopathic; Hydrocephalus - adult; Hydrocephalus - communicating; Dementia - hydrocephalus; NPH ... Ferri FF. Normal pressure hydrocephalus. In: Ferri FF, ed. ... Elsevier; 2016:chap 648. Rosenberg GA. Brain edema and disorders ...

  9. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  10. Normal growth and development

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002456.htm Normal growth and development To use the sharing features on this page, please enable JavaScript. A child's growth and development can be divided into four periods: ...

  11. Study on the metabolism of physiological amounts of Cr(III) intragastrical administration in normal rats using activable enriched stable isotope Cr-50 compound as a tracer

    International Nuclear Information System (INIS)

    Feng, W.Y.; Ding, W.J.; Qian, Q.F.; Chai, Z.F.

    1998-01-01

    In order to study the metabolism of physiological amounts of 51 Cr (10μg/100 g of body wt.) intragastrically administered in rats, the activable enriched stable isotope Cr-50 compound Cr 2 O 3 was used as a tracer. The absorption and distribution of 51 Cr(III) in rats with time were studied. Significant 51 Cr contents were found in all the organs and tissues of interest. The kidney, liver and bone contain higher amounts of 51 Cr than others. The fact that specific activities of 51 Cr are notably high in kidney, bone, spleen and pancreas and decrease gradually with time suggests that there are tighter binding of chromium in these organs. The excretion of 51 Cr at various time intervals was also studied. Almost totally intragastrically administered dose was excreted in the feces. The increased urinary excretion of 51 Cr with time indicates that the urine-chromium is the metabolic derivative of organism. In view of the tissues distribution and excretion, it can be concluded that no more than 1% of the dose was absorbed from the gastrointestinal tract. (author)

  12. Normalization of EEG activity among previously institutionalized children placed into foster care: A 12-year follow-up of the Bucharest Early Intervention Project.

    Science.gov (United States)

    Vanderwert, Ross E; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A

    2016-02-01

    Extreme social and cognitive deprivation as a result of institutional care has profound effects on developmental outcomes across multiple domains for many abandoned or orphaned children. The Bucharest Early Intervention Project (BEIP) examines the outcomes for children originally placed in institutions who were assessed comprehensively and then randomized to foster care (FCG) or care as usual (CAUG) and followed longitudinally. Here we report on the brain electrical activity (electroencephalogram: EEG) of 12-year-old children enrolled in the BEIP. Previous reports suggested improvement in resting EEG activity for the group of children placed in the foster care intervention, particularly those placed before 24 months of age compared to children who were randomized to CAUG or those placed into families after this age. At 12 years, differences between those in the FCG and those in the CAUG persist in the alpha band (8-13 Hz), but not in higher frequency bands (i.e. in the beta band; 15-30 Hz), except in those children placed into the FCG who remained in high quality care environments over the course of the study. These findings highlight the importance of maintaining a stable high quality caregiving environment, particularly for children exposed to early psychosocial deprivation, for promoting healthy brain development. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Activation status of Wnt/ß-catenin signaling in normal and neoplastic breast tissues: relationship to HER2/neu expression in human and mouse.

    Directory of Open Access Journals (Sweden)

    Sara Khalil

    Full Text Available Wnt/ß-catenin signaling is strongly implicated in neoplasia, but the role of this pathway in human breast cancer has been controversial. Here, we examined Wnt/ß-catenin pathway activation as a function of breast cancer progression, and tested for a relationship with HER2/neu expression, using a human tissue microarray comprising benign breast tissues, ductal carcinoma in situ (DCIS, and invasive carcinomas. Cores were scored for membranous ß-catenin, a key functional component of adherens junctions, and for nucleocytoplasmic ß-catenin, a hallmark of Wnt/ß-catenin pathway activation. Only 82% of benign samples exhibited membrane-associated ß-catenin, indicating a finite frequency of false-negative staining. The frequency of membrane positivity was similar in DCIS samples, but was significantly reduced in carcinomas (45%, P<0.001, consistent with loss of adherens junctions during acquisition of invasiveness. Negative membrane status in cancers correlated with higher grade (P = 0.04 and estrogen receptor-negative status (P = 0.03, both indices of poor prognosis. Unexpectedly, a substantial frequency of nucleocytoplasmic ß-catenin was observed in benign breast tissues (36%, similar to that in carcinomas (35%. Positive-staining basal nuclei observed in benign breast may identify putative stem cells. An increased frequency of nucleocytoplasmic ß-catenin was observed in DCIS tumors (56%, suggesting that pathway activation may be an early event in human breast neoplasia. A correlation was observed between HER2/neu expression and nucleocytoplasmic ß-catenin in node-positive carcinomas (P = 0.02. Furthermore, cytoplasmic ß-catenin was detected in HER2/neu-induced mouse mammary tumors. The Axin2(NLSlacZ mouse strain, a previously validated reporter of mammary Wnt/ß-catenin signaling, was utilized to define in vivo transcriptional consequences of HER2/neu-induced ß-catenin accumulation. Discrete hyperplastic foci observed in mammary

  14. Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: pharmacodynamic evaluation and comparison with isogenic normal-phenotype and revertant strains.

    Science.gov (United States)

    Nguyen, Hoang Anh; Denis, Olivier; Vergison, Anne; Theunis, Anne; Tulkens, Paul M; Struelens, Marc J; Van Bambeke, Françoise

    2009-04-01

    Small-colony variant (SCV) strains of Staphylococcus aureus show reduced antibiotic susceptibility and intracellular persistence, potentially explaining therapeutic failures. The activities of oxacillin, fusidic acid, clindamycin, gentamicin, rifampin, vancomycin, linezolid, quinupristin-dalfopristin, daptomycin, tigecycline, moxifloxacin, telavancin, and oritavancin have been examined in THP-1 macrophages infected by a stable thymidine-dependent SCV strain in comparison with normal-phenotype and revertant isogenic strains isolated from the same cystic fibrosis patient. The SCV strain grew slowly extracellularly and intracellularly (1- and 0.2-log CFU increase in 24 h, respectively). In confocal and electron microscopy, SCV and the normal-phenotype bacteria remain confined in acid vacuoles. All antibiotics tested, except tigecycline, caused a net reduction in bacterial counts that was both time and concentration dependent. At an extracellular concentration corresponding to the maximum concentration in human serum (total drug), oritavancin caused a 2-log CFU reduction at 24 h; rifampin, moxifloxacin, and quinupristin-dalfopristin caused a similar reduction at 72 h; and all other antibiotics had only a static effect at 24 h and a 1-log CFU reduction at 72 h. In concentration dependence experiments, response to oritavancin was bimodal (two successive plateaus of -0.4 and -3.1 log CFU); tigecycline, moxifloxacin, and rifampin showed maximal effects of -1.1 to -1.7 log CFU; and the other antibiotics produced results of -0.6 log CFU or less. Addition of thymidine restored intracellular growth of the SCV strain but did not modify the activity of antibiotics (except quinupristin-dalfopristin). All drugs (except tigecycline and oritavancin) showed higher intracellular activity against normal or revertant phenotypes than against SCV strains. The data may help rationalizing the design of further studies with intracellular SCV strains.

  15. The sodium channel activator Lu AE98134 normalizes the altered firing properties of fast spiking interneurons in Dlx5/6+/- mice

    DEFF Research Database (Denmark)

    von Schoubye, Nadia Lybøl; Frederiksen, Kristen; Kristiansen, Uffe

    2018-01-01

    Mental disorders such as schizophrenia are associated with impaired firing properties of fast spiking inhibitory interneurons (FSINs) causing reduced task-evoked gamma-oscillation in prefrontal cortex. The voltage-gated sodium channel NaV1.1 is highly expressed in PV-positive interneurons, but only...... at low levels in principal cells. Positive modulators of Nav1.1 channels are for this reason considered potential candidates for the treatment of cognitive disorders. Here we examined the effect of the novel positive modulator of voltage-gated sodium channels Lu AE98134. We found that Lu AE98134...... facilitated the sodium current mediated by NaV1.1 expressed in HEK cells by shifting its activation to more negative values, decreasing its inactivation kinetics and promoting a persistent inward current. In a slice preparation from the brain of adult mice, Lu AE98134 promoted the excitability of fast spiking...

  16. Succinate dehydrogenase assembly factor 2 is needed for assembly and activity of mitochondrial complex II and for normal root elongation in Arabidopsis.

    Science.gov (United States)

    Huang, Shaobai; Taylor, Nicolas L; Ströher, Elke; Fenske, Ricarda; Millar, A Harvey

    2013-02-01

    Mitochondria complex II (succinate dehydrogenase, SDH) plays a central role in respiratory metabolism as a component of both the electron transport chain and the tricarboxylic acid cycle. We report the identification of an SDH assembly factor by analysis of T-DNA insertions in At5g51040, a protein with unknown function that was identified by mass spectrometry analysis as a low abundance mitochondrial protein. This gene is co-expressed with a number of genes encoding mitochondrial proteins, including SDH1-1, and has low partial sequence similarity to human SDHAF2, a protein required for flavin-adenine dinucleotide (FAD) insertion into SDH. In contrast to observations of other SDH deficient lines in Arabidopsis, the sdhaf2 line did not affect photosynthetic rate or stomatal conductance, but instead showed inhibition of primary root elongation with early lateral root emergence, presumably due to the low SDH activity caused by the reduced abundance of SDHAF2. Both roots and leaves showed succinate accumulation but different responses in the abundance of other organic acids and amino acids assayed. Isolated mitochondria showed lowered SDH1 protein abundance, lowered maximal SDH activity and less protein-bound flavin-adenine dinucleotide (FAD) at the molecular mass of SDH1 in the gel separation. The short root phenotype and SDH function of sdhaf2 was fully complemented by transformation with SDHAF2. Application of the SDH inhibitor, malonate, phenocopied the sdhaf2 root architecture in WT. Whole root respiratory assays showed no difference between WT and sdhaf2, but micro-respirometry of the tips of roots clearly showed low oxygen consumption in sdhaf2 which could explain a metabolic deficit responsible for root tip growth. © 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.

  17. Modulation of the activity of vasopressinergic neurons by estrogen in rats refed with normal or sodium-free food after fasting.

    Science.gov (United States)

    Lucio-Oliveira, F; Traslaviña, G A A; Borges, B D B; Franci, C R

    2015-01-22

    Feeding increases plasma osmolality and ovarian steroids may influence the balance of fluids. Vasopressin (AVP) neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) express estrogen receptor type β (ERβ), but not estrogen receptor type α (ERα). The circumventricular organs express ERα and project efferent fibers to the PVN and SON. Our aim was to assess whether interactions exist between food state-related osmolality changes and the action of estrogen on AVP neuron activity and estrogen receptor expression. We assessed plasma osmolality and AVP levels; fos-coded protein (FOS)- and AVP-immunoreactivity (-IR) and FOS-IR and ERα-IR in the median preoptic nucleus (MnPO) and organ vasculosum lamina terminalis (OVLT) in estrogen-primed and unprimed ovariectomized rats under the provision of ad libitum food, 48h of fasting, and subsequent refeeding with standard chow or sodium-free food. Refeeding with standard chow increased plasma osmolality and AVP as well as the co-expression of FOS-IR/AVP-IR in the PVN and SON. These responses were not altered by estrogen, with the exception of the decreases in FOS-IR/AVP-IR in the lateral PVN. During refeeding, estrogen modulates only a subpopulation of AVP neurons in the lateral PVN. FOS-ERα co-expression in the ventral median preoptic nucleus (vMnPO) was reduced by estrogen and increased after refeeding with standard chow following fasting. It appears that estrogen may indirectly modulate the activity of AVP neurons, which are involved in the mechanism affected by hyperosmolality-induced refeeding after fasting. This indirect action of estrogen can be at least in part via ERα in the vMnPO. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Smooth quantile normalization.

    Science.gov (United States)

    Hicks, Stephanie C; Okrah, Kwame; Paulson, Joseph N; Quackenbush, John; Irizarry, Rafael A; Bravo, Héctor Corrada

    2018-04-01

    Between-sample normalization is a critical step in genomic data analysis to remove systematic bias and unwanted technical variation in high-throughput data. Global normalization methods are based on the assumption that observed variability in global properties is due to technical reasons and are unrelated to the biology of interest. For example, some methods correct for differences in sequencing read counts by scaling features to have similar median values across samples, but these fail to reduce other forms of unwanted technical variation. Methods such as quantile normalization transform the statistical distributions across samples to be the same and assume global differences in the distribution are induced by only technical variation. However, it remains unclear how to proceed with normalization if these assumptions are violated, for example, if there are global differences in the statistical distributions between biological conditions or groups, and external information, such as negative or control features, is not available. Here, we introduce a generalization of quantile normalization, referred to as smooth quantile normalization (qsmooth), which is based on the assumption that the statistical distribution of each sample should be the same (or have the same distributional shape) within biological groups or conditions, but allowing that they may differ between groups. We illustrate the advantages of our method on several high-throughput datasets with global differences in distributions corresponding to different biological conditions. We also perform a Monte Carlo simulation study to illustrate the bias-variance tradeoff and root mean squared error of qsmooth compared to other global normalization methods. A software implementation is available from https://github.com/stephaniehicks/qsmooth.

  19. Nattokinase-promoted tissue plasminogen activator release from human cells.

    Science.gov (United States)

    Yatagai, Chieko; Maruyama, Masugi; Kawahara, Tomoko; Sumi, Hiroyuki

    2008-01-01

    When heated to a temperature of 70 degrees C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121 degrees C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration. Copyright 2009 S. Karger AG, Basel.

  20. Monitoring the normal body

    DEFF Research Database (Denmark)

    Nissen, Nina Konstantin; Holm, Lotte; Baarts, Charlotte

    2015-01-01

    of practices for monitoring their bodies based on different kinds of calculations of weight and body size, observations of body shape, and measurements of bodily firmness. Biometric measurements are familiar to them as are health authorities' recommendations. Despite not belonging to an extreme BMI category...... provides us with knowledge about how to prevent future overweight or obesity. This paper investigates body size ideals and monitoring practices among normal-weight and moderately overweight people. Methods : The study is based on in-depth interviews combined with observations. 24 participants were...... recruited by strategic sampling based on self-reported BMI 18.5-29.9 kg/m2 and socio-demographic factors. Inductive analysis was conducted. Results : Normal-weight and moderately overweight people have clear ideals for their body size. Despite being normal weight or close to this, they construct a variety...

  1. Efficacy of a family practice-based lifestyle intervention program to increase physical activity and reduce clinical and physiological markers of vascular health in patients with high normal blood pressure and/or high normal blood glucose (SNAC: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Overend Tom

    2011-02-01

    Full Text Available Abstract Background Previous interventions to increase physical activity and reduce cardiovascular risk factors have been targeted at individuals with established disease; less attention has been given to intervention among individuals with high risk for disease nor has there been determination of the influence of setting in which the intervention is provided. In particular, family practice represents an ideal setting for the provision and long-term maintenance of lifestyle interventions for patients at risk (ie high-normal blood pressure or impaired glucose tolerance. Methods/design The Staged Nutrition and Activity Counseling (SNAC study is a randomized clustered design clinical trial that will investigate the effectiveness and efficacy of a multi-component lifestyle intervention on cardiovascular disease risk factors and vascular function in patients at risk in primary care. Patients will be randomized by practice to either a standard of care lifestyle intervention or a behaviourally-based, matched prescriptive physical activity and diet change program. The primary goal is to increase physical activity and improve dietary intake according to Canada's Guides to Physical Activity Healthy Eating over 24 months. The primary intention to treat analysis will compare behavioral, physiological and metabolic outcomes at 6, 12 and 24 months post-randomization including estimation of incident hypertension and/or diabetes. Discussion The design features of our trial, and the practical problems (and solutions associated with implementing these design features, particularly those that result in potential delay between recruitment, baseline data collection, randomization, intervention, and assessment will be discussed. Results of the SNAC trial will provide scientific rationale for the implementation of this lifestyle intervention in primary care. Trial registration ISRCTN: ISRCTN:42921300

  2. Endothelial Ca+-activated K+ channels in normal and impaired EDHF-dilator responses--relevance to cardiovascular pathologies and drug discovery.

    Science.gov (United States)

    Grgic, Ivica; Kaistha, Brajesh P; Hoyer, Joachim; Köhler, Ralf

    2009-06-01

    The arterial endothelium critically contributes to blood pressure control by releasing vasodilating autacoids such as nitric oxide, prostacyclin and a third factor or pathway termed 'endothelium-derived hyperpolarizing factor' (EDHF). The nature of EDHF and EDHF-signalling pathways is not fully understood yet. However, endothelial hyperpolarization mediated by the Ca(2+)-activated K(+) channels (K(Ca)) has been suggested to play a critical role in initializing EDHF-dilator responses in conduit and resistance-sized arteries of many species including humans. Endothelial K(Ca) currents are mediated by the two K(Ca) subtypes, intermediate-conductance K(Ca) (KCa3.1) (also known as, a.k.a. IK(Ca)) and small-conductance K(Ca) type 3 (KCa2.3) (a.k.a. SK(Ca)). In this review, we summarize current knowledge about endothelial KCa3.1 and KCa2.3 channels, their molecular and pharmacological properties and their specific roles in endothelial function and, particularly, in the EDHF-dilator response. In addition we focus on recent experimental evidences derived from KCa3.1- and/or KCa2.3-deficient mice that exhibit severe defects in EDHF signalling and elevated blood pressures, thus highlighting the importance of the KCa3.1/KCa2.3-EDHF-dilator system for blood pressure control. Moreover, we outline differential and overlapping roles of KCa3.1 and KCa2.3 for EDHF signalling as well as for nitric oxide synthesis and discuss recent evidence for a heterogeneous (sub) cellular distribution of KCa3.1 (at endothelial projections towards the smooth muscle) and KCa2.3 (at inter-endothelial borders and caveolae), which may explain their distinct roles for endothelial function. Finally, we summarize the interrelations of altered KCa3.1/KCa2.3 and EDHF system impairments with cardiovascular disease states such as hypertension, diabetes, dyslipidemia and atherosclerosis and discuss the therapeutic potential of KCa3.1/KCa2.3 openers as novel types of blood pressure-lowering drugs.

  3. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process......This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...

  4. Normalization of satellite imagery

    Science.gov (United States)

    Kim, Hongsuk H.; Elman, Gregory C.

    1990-01-01

    Sets of Thematic Mapper (TM) imagery taken over the Washington, DC metropolitan area during the months of November, March and May were converted into a form of ground reflectance imagery. This conversion was accomplished by adjusting the incident sunlight and view angles and by applying a pixel-by-pixel correction for atmospheric effects. Seasonal color changes of the area can be better observed when such normalization is applied to space imagery taken in time series. In normalized imagery, the grey scale depicts variations in surface reflectance and tonal signature of multi-band color imagery can be directly interpreted for quantitative information of the target.

  5. The normal holonomy group

    International Nuclear Information System (INIS)

    Olmos, C.

    1990-05-01

    The restricted holonomy group of a Riemannian manifold is a compact Lie group and its representation on the tangent space is a product of irreducible representations and a trivial one. Each one of the non-trivial factors is either an orthogonal representation of a connected compact Lie group which acts transitively on the unit sphere or it is the isotropy representation of a single Riemannian symmetric space of rank ≥ 2. We prove that, all these properties are also true for the representation on the normal space of the restricted normal holonomy group of any submanifold of a space of constant curvature. 4 refs

  6. Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

    Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II

  7. Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces cell proliferation in normal human bronchial epithelial cells through NFκB activation and cyclin D1 up-regulation

    International Nuclear Information System (INIS)

    Ho, Y.-S.; Chen, Chien-Ho; Wang, Y.-J.; Pestell, Richard G.; Albanese, Chris; Chen, R.-J.; Chang, M.-C.; Jeng, J.-H.; Lin, S.-Y.; Liang, Y.-C.; Tseng, H.; Lee, W.-S.; Lin, J.-K.; Chu, J.-S.; Chen, L.-C.; Lee, C.-H.; Tso, W.-L.; Lai, Y.-C.; Wu, C.-H.

    2005-01-01

    Cigarette smoke contains several carcinogens known to initiate and promote tumorigenesis as well as metastasis. Nicotine is one of the major components of the cigarette smoke and the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific carcinogen. Here, we demonstrated that NNK stimulated cell proliferation in normal human bronchial epithelial cells (NHBE) and small airway epithelial cells (SAEC). Cells exposed to NNK resulted in an increase in the level of cyclin D1 protein (as early as 3-6 h). Increased phosphorylation of the Rb Ser 795 was detected at 6-15 h after NNK treatment and thereby promoted cells entering into the S phase (at 15-21 h). The increased cyclin D1 protein level was induced through activation of the transcription factor, nuclear factor kB (NFκB), in the NHBE cells. Treatment of the NHBE cells with PD98059, an ERK1/2 (extracellular signal-regulated protein kinase)-specific inhibitor, specifically suppressed the NNK-induced IκBα phosphorylation at position 32 of the serine residue, suggesting that the ERK1/2 kinase was involved in the IκBα phosphorylation induced by NFκB activation. To determine whether the NNK-induced NFκB activation and cyclin D1 induction were also observed in vivo, A/J mice were treated with NNK (9.1 mg) for 20 weeks and the results showed a significant induction of cyclin D1 and NFκB translocation determined by immunoblotting analyses. We further demonstrated that the nicotine acetylcholine receptor (nAchR), which contains the α3-subunit, was the major target mediating NNK-induced cyclin D1 expression in the NHBE cells. In summary, our findings demonstrate for the first time that NNK could stimulate normal human bronchial cell proliferation through activation of the NFκB, which in turn up-regulated the cyclin D1 expression

  8. Normality in Analytical Psychology

    Directory of Open Access Journals (Sweden)

    Steve Myers

    2013-11-01

    Full Text Available Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity.

  9. Medically-enhanced normality

    DEFF Research Database (Denmark)

    Møldrup, Claus; Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

    2003-01-01

    Objective: To consider public perspectives on the use of medicines for non-medical purposes, a usage called medically-enhanced normality (MEN). Method: Examples from the literature were combined with empirical data derived from two Danish research projects: a Delphi internet study and a Telebus...

  10. The Normal Fetal Pancreas.

    Science.gov (United States)

    Kivilevitch, Zvi; Achiron, Reuven; Perlman, Sharon; Gilboa, Yinon

    2017-10-01

    The aim of the study was to assess the sonographic feasibility of measuring the fetal pancreas and its normal development throughout pregnancy. We conducted a cross-sectional prospective study between 19 and 36 weeks' gestation. The study included singleton pregnancies with normal pregnancy follow-up. The pancreas circumference was measured. The first 90 cases were tested to assess feasibility. Two hundred ninety-seven fetuses of nondiabetic mothers were recruited during a 3-year period. The overall satisfactory visualization rate was 61.6%. The intraobserver and interobserver variability had high interclass correlation coefficients of of 0.964 and 0.967, respectively. A cubic polynomial regression described best the correlation of pancreas circumference with gestational age (r = 0.744; P pancreas circumference percentiles for each week of gestation were calculated. During the study period, we detected 2 cases with overgrowth syndrome and 1 case with an annular pancreas. In this study, we assessed the feasibility of sonography for measuring the fetal pancreas and established a normal reference range for the fetal pancreas circumference throughout pregnancy. This database can be helpful when investigating fetomaternal disorders that can involve its normal development. © 2017 by the American Institute of Ultrasound in Medicine.

  11. C-Reactive Protein Concentrations and Level of Physical Activity in Men and Women With Normal and Impaired Glucose Tolerance. A Cross-Sectional Population-Based Study in Sweden.

    Science.gov (United States)

    Hellgren, Margareta I; Larsson, Charlotte A; Daka, Bledar; Petzold, Max; Jansson, Per-Anders; Lindblad, Ulf

    2016-06-01

    We aimed to explore the association between self-reported leisure time physical activity (LTPA) and C-reactive protein (CRP) concentrations in men and women with and without impaired glucose tolerance (IGT). In a cross-sectional study, a random sample (n = 2,816) was examined with an oral glucose tolerance test, CRP and information about LTPA. Those with IGT or normal glucose tolerance (NGT) and CRP value ≤10 mg/L were selected (n = 2,367) for the study. An inverse association between LTPA and CRP concentrations was observed in the population (P men with IGT (P = .023) and in women with NGT. Men with IGT, reporting slight physical activity up to 4 hours a week presented significantly higher CRP concentrations than normoglycemic men (Δ0.6 mg/L, P = .004). However, this difference could not be found in men with IGT reporting more intense physical activity (Δ0.01 mg/L, P = .944). Physical inactivity seems to have greater inflammatory consequences for men (vs. women) with IGT. More importantly, although 4 hours of physical activity per week is more than the usual minimum recommendation, an even greater intensity of LTPA appears to be required to limit subclinical inflammation in men with IGT.

  12. The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-I levels

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Williams, Scott M.; Hebert, Patricia R.; Coffey, Christopher S.; Hillege, Hans L.; Navis, Gerjan; Vaughan, Douglas E.; van Gilst, Wiek H.; Moore, Jason H.

    2006-01-01

    Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor I (PAI-I) directly influence thrombus formation and degradation and thus risk for arterial thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI-I levels in a large population-based sample from the

  13. Idiopathic Normal Pressure Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Basant R. Nassar BS

    2016-04-01

    Full Text Available Idiopathic normal pressure hydrocephalus (iNPH is a potentially reversible neurodegenerative disease commonly characterized by a triad of dementia, gait, and urinary disturbance. Advancements in diagnosis and treatment have aided in properly identifying and improving symptoms in patients. However, a large proportion of iNPH patients remain either undiagnosed or misdiagnosed. Using PubMed search engine of keywords “normal pressure hydrocephalus,” “diagnosis,” “shunt treatment,” “biomarkers,” “gait disturbances,” “cognitive function,” “neuropsychology,” “imaging,” and “pathogenesis,” articles were obtained for this review. The majority of the articles were retrieved from the past 10 years. The purpose of this review article is to aid general practitioners in further understanding current findings on the pathogenesis, diagnosis, and treatment of iNPH.

  14. Normal Weight Dyslipidemia

    DEFF Research Database (Denmark)

    Ipsen, David Hojland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-01-01

    Objective: The liver coordinates lipid metabolism and may play a vital role in the development of dyslipidemia, even in the absence of obesity. Normal weight dyslipidemia (NWD) and patients with nonalcoholic fatty liver disease (NAFLD) who do not have obesity constitute a unique subset...... of individuals characterized by dyslipidemia and metabolic deterioration. This review examined the available literature on the role of the liver in dyslipidemia and the metabolic characteristics of patients with NAFLD who do not have obesity. Methods: PubMed was searched using the following keywords: nonobese......, dyslipidemia, NAFLD, NWD, liver, and metabolically obese/unhealthy normal weight. Additionally, article bibliographies were screened, and relevant citations were retrieved. Studies were excluded if they had not measured relevant biomarkers of dyslipidemia. Results: NWD and NAFLD without obesity share a similar...

  15. Ethics and "normal birth".

    Science.gov (United States)

    Lyerly, Anne Drapkin

    2012-12-01

    The concept of "normal birth" has been promoted as ideal by several international organizations, although debate about its meaning is ongoing. In this article, I examine the concept of normalcy to explore its ethical implications and raise a trio of concerns. First, in its emphasis on nonuse of technology as a goal, the concept of normalcy may marginalize women for whom medical intervention is necessary or beneficial. Second, in its emphasis on birth as a socially meaningful event, the mantra of normalcy may unintentionally avert attention to meaning in medically complicated births. Third, the emphasis on birth as a normal and healthy event may be a contributor to the long-standing tolerance for the dearth of evidence guiding the treatment of illness during pregnancy and the failure to responsibly and productively engage pregnant women in health research. Given these concerns, it is worth debating not just what "normal birth" means, but whether the term as an ideal earns its keep. © 2012, Copyright the Authors Journal compilation © 2012, Wiley Periodicals, Inc.

  16. Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue.

    Science.gov (United States)

    Chetrite, Gérard S; Cortes-Prieto, Joaquin; Pasqualini, Jorge R

    2011-12-01

    Tibolone (Org-OD14) is the active substance of Livial®, a synthetic steroid with the structure 7α,17α-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, possessing weak tissue-specific estrogenic, progestogenic, and androgenic properties, used to treat menopausal complaints. After oral administration, tibolone is extensively metabolized into the 3α-(Org-4904) and 3β-(Org-30126) hydroxy derivatives with estrogenic properties, its 4-ene (Org-OM38) isomer with progestogenic/androgenic activities, and the 3α-sulfate (Org-34322) derivative, a major biologically inactive circulating form. We compared the dose response of tibolone and its metabolites on estrone sulfatase activity [conversion of estrone sulfate (E1S) to estrone (E1)] in normal and cancerous human breast tissues. Tissue minces were incubated with physiological concentrations of [3H]-E1S (5×10-9M) alone or in the presence of tibolone and its metabolites (concentration range: 5×10-7to 5×10-5M) for 4 h. Tritiated E1, estradiol (E2), and E1S were separated and evaluated quantitatively by thin-layer chromatography. The sulfatase activity was significantly higher in cancerous breast but strongly inhibited by tibolone and the different metabolites, whereas 3α- and 3β-hydroxy derivatives were the most potent inhibitors. This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients.

  17. Strength of Gamma Rhythm Depends on Normalization

    Science.gov (United States)

    Ray, Supratim; Ni, Amy M.; Maunsell, John H. R.

    2013-01-01

    Neuronal assemblies often exhibit stimulus-induced rhythmic activity in the gamma range (30–80 Hz), whose magnitude depends on the attentional load. This has led to the suggestion that gamma rhythms form dynamic communication channels across cortical areas processing the features of behaviorally relevant stimuli. Recently, attention has been linked to a normalization mechanism, in which the response of a neuron is suppressed (normalized) by the overall activity of a large pool of neighboring neurons. In this model, attention increases the excitatory drive received by the neuron, which in turn also increases the strength of normalization, thereby changing the balance of excitation and inhibition. Recent studies have shown that gamma power also depends on such excitatory–inhibitory interactions. Could modulation in gamma power during an attention task be a reflection of the changes in the underlying excitation–inhibition interactions? By manipulating the normalization strength independent of attentional load in macaque monkeys, we show that gamma power increases with increasing normalization, even when the attentional load is fixed. Further, manipulations of attention that increase normalization increase gamma power, even when they decrease the firing rate. Thus, gamma rhythms could be a reflection of changes in the relative strengths of excitation and normalization rather than playing a functional role in communication or control. PMID:23393427

  18. Theory of normal metals

    International Nuclear Information System (INIS)

    Mahan, G.D.

    1992-01-01

    The organizers requested that I give eight lectures on the theory of normal metals, ''with an eye on superconductivity.'' My job was to cover the general properties of metals. The topics were selected according to what the students would need to known for the following lectures on superconductivity. My role was to prepare the ground work for the later lectures. The problem is that there is not yet a widely accepted theory for the mechanism which pairs the electrons. Many mechanisms have been proposed, with those of phonons and spin fluctuations having the most followers. So I tried to discuss both topics. I also introduced the tight-binding model for metals, which forms the basis for most of the work on the cuprate superconductors

  19. Geomorphic and Structural Evidence for Rolling Hinge Style Deformation in the Footwall of an Active Low Angle Normal Fault, Mai'iu Fault, Woodlark Rift, SE Papua New Guinea

    Science.gov (United States)

    Mizera, M.; Little, T.; Norton, K. P.; Webber, S.; Ellis, S. M.; Oesterle, J.

    2016-12-01

    While shown to operate in oceanic crust, rolling hinge style deformation remains a debated process in metamorpic core complexes (MCCs) in the continents. The model predicts that unloading and isostatic uplift during slip causes a progressive back-tilting in the upper crust of a normal fault that is more steeply dipping at depth. The Mai'iu Fault in the Woodlark Rift, SE Papua New Guinea, is one of the best-exposed and fastest slipping (probably >7 mm/yr) active low-angle normal faults (LANFs) on Earth. We analysed structural field data from this fault's exhumed slip surface and footwall, together with geomorphic data interpreted from aerial photographs and GeoSAR-derived digital elevation models (gridded at 5-30 m spacing), to evaluate deformational processes affecting the rapidly exhuming, domal-shaped detachment fault. The exhumed fault surface emerges from the ground at the rangefront near sea level with a northward dip of 21°. Up-dip, it is well-preserved, smooth and corrugated, with some fault remnants extending at least 29 km in the slip direction. The surface flattens over the crest of the dome, beyond where it dips S at up to 15°. Windgaps perched on the crestal main divide of the dome, indicate both up-dip tectonic advection and progressive back-tilting of the exhuming fault surface. We infer that slip on a serial array of m-to-km scale up-to-the-north, steeply S-dipping ( 75°) antithetic-sense normal faults accommodated some of the exhumation-related, inelastic bending of the footwall. These geomorphically well expressed faults strike parallel to the main Mai'iu fault at 110.9±5°, have a mean cross-strike spacing of 1520 m, and slip with a consistent up-to-the-north sense of throw ranging from <5 m to 120 m. Apparently the Mai'iu Fault was able to continue slipping despite having to negotiate this added fault-roughness. We interpret the antithetic faulting to result from bending stresses, and to provide the first clear examples of rolling hinge

  20. Asn12 and Asn278: Critical Residues for In Vitro Biological Activity of Reteplase

    Directory of Open Access Journals (Sweden)

    Naganath Mandi

    2010-01-01

    Full Text Available Reteplase (rPA is a thrombolytic agent used for the treatment of acute myocardial infarction. We studied the expression of rPA and its selected asparagine mutants after integration into the Pichia genome. Though methanol induction of the native and the rPA mutants showed similar expression levels (~200–250 mg/L, the mutants displayed significant loss of protease activity. Strikingly, the clot lysis activities of these mutants were considerably different. While mutation of Asn12 (N12P of the Kringle 2 domain showed delayed clot lysis activity (1/2=38 min compared to the native rPA (1/2=33 min, a faster rate of clot lysis (1/2=27 min was observed when the Asn278 (N278S of the serine protease domain was mutated. Interestingly, the slowest clot lysis activity (1/2=49 min demonstrated by the double mutant (N12P, N278S suggests the dominant role of Asn12 in regulating the fibrinolytic activity of rPA. The results presented in this paper indicate that the fibrinolytic and the proteolytic activities of rPA are independent of each other.

  1. Improving the activity of the subtilisin nattokinase by site-directed mutagenesis and molecular dynamics simulation.

    Science.gov (United States)

    Weng, Meizhi; Deng, Xiongwei; Bao, Wei; Zhu, Li; Wu, Jieyuan; Cai, Yongjun; Jia, Yan; Zheng, Zhongliang; Zou, Guolin

    2015-09-25

    Nattokinase (NK), a bacterial serine protease from Bacillus subtilis var. natto, is a potential cardiovascular drug exhibiting strong fibrinolytic activity. To broaden its commercial and medical applications, we constructed a single-mutant (I31L) and two double-mutants (M222A/I31L and T220S/I31L) by site-directed mutagenesis. Active enzymes were expressed in Escherichia coli with periplasmic secretion and were purified to homogeneity. The kinetic parameters of enzymes were examined by spectroscopy assay and isothermal titration calorimetry (ITC), and their fibrinolytic activities were determined by fibrin plate method. The substitution of Leu(31) for Ile(31) resulted in about 2-fold enhancement of catalytic efficiency (Kcat/KM) compared with wild-type NK. The specific activities of both double-mutants (M222A/I31L and T220S/I31L) were significantly increased when compared with the single-mutants (M222A and T220S) and the oxidative stability of M222A/I31L mutant was enhanced with respect to wild-type NK. This study demonstrates the feasibility of improving activity of NK by site-directed mutagenesis and shows successful protein engineering cases to improve the activity of NK as a potent therapeutic agent. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Association of plasminogen activator inhibitor-1 and angiotensin converting enzyme polymorphisms with recurrent pregnancy loss in Iranian women

    Directory of Open Access Journals (Sweden)

    Fatemeh Shakarami

    2015-10-01

    Full Text Available Background: Recurrent pregnancy loss (RPL defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1 and angiotensin converting enzyme (ACE genes are closely related to fibrinolytic process, embryonic development and pregnancy success. Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes. Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I polymorphism was determined by PCR-RFLP. Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%, and 5 controls (5% (p=0.006 so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84. In addition, 7 patients (7 %, and no one from the control group, were homozygote (I/I for ACE polymorphism (p=0.034, suggesting no significant associations between ACE D allele or DD genotype and RPL. Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL.

  3. Adenosine deaminase organic effect in normal and abnormal cerebrospinal fluid

    International Nuclear Information System (INIS)

    Hamad, A.M.; Samarai, M.A.

    2007-01-01

    To study the effect of the organic substances on adenosine deaminase (ADA) activity in normal and abnormal cerebrospinal fluid (CSF). Various concentrations of 2-mercaptopurine, Ame-tycine, Adenosine analogues (Guanine, Thymine) and ATP were tested to see their effect on ADA activity in normal and abnormal CSF. ADA activity in normal and abnormal CSF was remarkably decreased with the increasing of concentrations of substances tested. These effects may have important therapeutic implications. (author)

  4. A new pro-migratory activity on human myogenic precursor cells for a synthetic peptide within the E domain of the mechano growth factor

    International Nuclear Information System (INIS)

    Mills, Philippe; Lafreniere, Jean-Francois; Benabdallah, Basma Fattouma; El Fahime, El Mostafa; Tremblay, Jacques-P.

    2007-01-01

    Duchenne muscular dystrophy (DMD) is an inherited disease that leads to progressive muscle wasting. Myogenic precursor cell transplantation is an approach that can introduce the normal dystrophin gene in the muscle fibers of the patients. Unfortunately, these myogenic precursor cells do not migrate well in the muscle and thus many injections have to be done to enable a good graft success. Recent reports have shown that there is extensive splicing of the IGF-1 gene in muscles. The MGF isoform contains a C-terminal 24 amino acids peptide in the E domain (MGF-Ct24E) that has intrinsic properties. It can promote the proliferation while delaying the differentiation of C 2 C 12 cells. Here, we demonstrated that this synthetic peptide is a motogenic factor for human precursor myogenic cells in vitro and in vivo. Indeed, MGF-Ct24E peptide can modulate members of the fibrinolytic and metalloproteinase systems, which are implicated in the migration of myogenic cells. MGF-Ct24E peptide enhances the expression of u-PA, u-PAR and MMP-7 while reducing PAI-1 activity. Moreover, it has no effect on the gelatinases MMP-2 and -9. Those combined effects can favour cell migration. Finally, we present some results suggesting that the MGF-Ct24E peptide induces these cell responses through a mechanism that does not involve the IGF-1 receptor. Thus, this MGF-Ct24E peptide has a new pro-migratory activity on human myogenic precursor cells that may be helpful in the treatment of DMD. Those results reinforce the possibility that the IGF-1Ec isoform may produce an E domain peptide that can act as a cytokine

  5. 正常人音乐欣赏的脑功能磁共振激活模式研究%The study of fMRI activation pattern of normal brain music appreciation

    Institute of Scientific and Technical Information of China (English)

    刘明; 赵晶; 和清源; 庞冉; 陈云翔; 王志群

    2016-01-01

    目的:采用血氧水平依赖的脑功能磁共振成像技术( BOLD-fMRI)技术,研究正常人欣赏欢快音乐时的脑功能区定位,探讨可能的神经网络调节机制。方法选择15例正常健康受试者,年龄25~50岁,在欣赏欢快音乐同时,用BOLD-fMRI技术进行脑功能磁共振成像检查,采用SPM软件对原始数据进行统计学处理,获得平均激活图,分析激活增高的脑区。结果15例受试者在欣赏欢快音乐时大脑显著激活了视觉注意网络、默认网络、运动感觉网络、认知记忆网络的相关脑区,这些脑区可能参与了音乐的感知、注意、记忆、情绪反应等过程。结论功能磁共振成像技术在音乐欣赏的功能定位方面具有独特的价值,欢快音乐欣赏可激活大脑多种功能神经网络参与处理。%Objective By using the blood oxygen level dependent functional magnetic resonance imaging ( BOLD-fMRI ) technique, to study the normal brain function localization when listening cheerful music , and then to explore the possible neural network adjustment mechanism .Methods We selected 15 volunteers with normal mental health , age between 25~50 .While listening the cheerful music , BOLD-fMRI examinations were performed and the original image data were obtained for statistical processing by using SPM software .And then, the average activation graph was analyzed to acquire the activated brain regions . Results While the subjects listening the cheerful music , several brain networks were activated including visual attention net-work, default mode network , sensorimoter network and cognitive network .These brain regions probably involved in the Music per-ception, attention, memory, and emotional reaction process .Conclusion The application of fMRI technique in music apprecia-tion has unique value in the respect of functional localization , cheerful music can activate the brain functions involved in several neural networks .

  6. Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients.

    Science.gov (United States)

    Pino-Otín, M R; Viñas, O; de la Fuente, M A; Juan, M; Font, J; Torradeflot, M; Pallarés, L; Lozano, F; Alberola-Ila, J; Martorell, J

    1995-03-15

    CD50 (ICAM-3) is a leukocyte differentiation Ag expressed almost exclusively on hemopoietic cells, with a key role in the first steps of immune response. To develop a specific sandwich ELISA to detect a soluble CD50 form (sCD50), two different mAbs (140-11 and 101-1D2) recognizing non-overlapping epitopes were used. sCD50 was detected in the supernatant of stimulated PBMCs, with the highest levels after CD3 triggering. Simultaneously, the CD50 surface expression diminished during the first 24 h. sCD50 isolated from culture supernatant and analyzed by immunoblotting showed an apparent m.w. of 95 kDa, slightly smaller than the membrane form. These data, together with Northern blot kinetics analysis, suggest that sCD50 is cleaved from cell membrane. Furthermore, we detect sCD50 in normal human sera and higher levels in sera of systemic lupus erythematosus (SLE) patients, especially in those in active phase. The sCD50 levels showed a positive correlation with sCD27 levels (r = 0.4213; p = 0.0026). Detection of sCD50, both after in vitro CD3 triggering of PBMCs and increased in SLE sera, suggests that sCD50 could be used as a marker of lymphocyte stimulation.

  7. Forced Normalization: Antagonism Between Epilepsy and Psychosis.

    Science.gov (United States)

    Kawakami, Yasuhiko; Itoh, Yasuhiko

    2017-05-01

    The antagonism between epilepsy and psychosis has been discussed for a long time. Landolt coined the term "forced normalization" in the 1950s to describe psychotic episodes associated with the remission of seizures and disappearance of epileptiform activity on electroencephalograms in individuals with epilepsy. Since then, neurologists and psychiatrists have been intrigued by this phenomenon. However, although collaborative clinical studies and basic experimental researches have been performed, the mechanism of forced normalization remains unknown. In this review article, we present a historical overview of the concept of forced normalization, and discuss potential pathogenic mechanisms and clinical diagnosis. We also discuss the role of dopamine, which appears to be a key factor in the mechanism of forced normalization. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Short proofs of strong normalization

    OpenAIRE

    Wojdyga, Aleksander

    2008-01-01

    This paper presents simple, syntactic strong normalization proofs for the simply-typed lambda-calculus and the polymorphic lambda-calculus (system F) with the full set of logical connectives, and all the permutative reductions. The normalization proofs use translations of terms and types to systems, for which strong normalization property is known.

  9. Dynamic changes in plasma tissue plasminogen activator, plasminogen activator inhibitor-1 and beta-thromboglobulin content in ischemic stroke.

    Science.gov (United States)

    Zhuang, Ping; Wo, Da; Xu, Zeng-Guang; Wei, Wei; Mao, Hui-ming

    2015-07-01

    The aim of this paper is to investigate the corresponding variations of plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities, and beta-thromboglobulin (β-TG) content in patients during different stages of ischemic stroke. Ischemic stroke is a common disease among aging people and its occurrence is associated with abnormalities in the fibrinolytic system and platelet function. However, few reports focus on the dynamic changes in the plasma fibrinolytic system and β-TG content in patients with ischemic stroke. Patients were divided into three groups: acute, convalescent and chronic. Plasma t-PA and PAI-1 activities were determined by chromogenic substrate analysis and plasma β-TG content was detected by radioimmunoassay. Patients in the acute stage of ischemic stroke had significantly increased levels of t-PA activity and β-TG content, but PAI-1 activity was significantly decreased. Negative correlations were found between plasma t-PA and PAI-1 activities and between plasma t-PA activity and β-TG content in patients with acute ischemic stroke. There were significant differences in plasma t-PA and PAI-1 activities in the aged control group, as well as in the acute, convalescent and chronic groups. It can be speculated that the increased activity of t-PA in patients during the acute stage was the result of compensatory function, and that the increase in plasma β-TG level not only implies the presence of ischemic stroke but is likely a cause of ischemic stroke. During the later stages of ischemic stroke, greater attention is required in monitoring levels of PAI-1. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Comparable attenuation of sympathetic nervous system activity in obese subjects with normal glucose tolerance, impaired glucose tolerance and treatment naïve type 2 diabetes following equivalent weight loss

    Directory of Open Access Journals (Sweden)

    Nora E. Straznicky

    2016-11-01

    Full Text Available Background and Purpose: Elevated sympathetic nervous system (SNS activity is a characteristic of obesity and type 2 diabetes (T2D that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n=15, impaired glucose tolerant (IGT, n=24 and newly-diagnosed T2D (n=15 consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate for 4-months. The three groups were matched for baseline age (56 + 1 years, body mass index (BMI, 32.9 + 0.7 kg/m2 and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography, spontaneous cardiac baroreflex sensitivity (BRS and oral glucose tolerance test. Results: Weight loss averaged -7.5 + 0.8, -8.1 + 0.5 and -8.0 + 0.9 % of body weight in NGT, IGT and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0-120 compared to NGT and IGT (group effect, P<0.001. Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group x time, P=0.04. The magnitude of reduction in MSNA (-7 + 3, -8 + 4, -15 + 4 burst/100hb, respectively and whole-body norepinephrine spillover rate (-28 + 8, -18 + 6 and -25 + 7 %, respectively, time effect both P<0.001, did not differ between groups. After adjustment for age and change in body weight, ∆ insulin AUC0-120 was independently associated with reduction in arterial norepinephrine concentration, whilst ∆ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA. Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects with different baseline glucose tolerance

  11. Efeito do extrato da casca de Syzygium cumini sobre a atividade da acetilcolinesterase em ratos normais e diabéticos Syzygium cumini bark extract effect on acetylcholinesterase activity in normal and diabetic rats

    Directory of Open Access Journals (Sweden)

    Cinthia Melazzo Mazzanti

    2004-06-01

    Full Text Available Este estudo verificou a eficiência do extrato etanólico da casca de Syzygium cumini sobre o sistema colinérgico de ratos normais e diabéticos induzidos com aloxano. Os animais foram divididos em grupo controle (C, tratado com Syzygium cumini (TS, diabético (D e diabético tratado com Syzygium cumini (DS. A atividade da acetilcolinesterase (AChE foi analisada nas seguintes estruturas cerebrais: cerebelo, córtex, estriado e hipocampo. O extrato etanólico da casca de Syzygium cumini na dose de 1g.kg-1 foi administrado diariamente por um período de trinta dias. Foi verificado após este período que o extrato inibiu a atividade da AChE no cerebelo e córtex cerebral dos ratos do grupo DS (PThe present study verified the efficiency of the bark ethanol extract of Syzygium cumini on the cholinergic system of normal and alloxan induced diabetic rats. Thirty-nine female rats were divided in control (C, treated with Syzygium cumini (TS, diabetic (D and diabetic treated with Syzygium cumini (DS. The activity of acetylcholinesterase (AChE was analyzed in the following cerebral structures: cerebellum, cortex, striatum and hippocampus. The extract of the bark of Syzygium cumini in the dose of 1g.kg-1 was administered orally daily for a period of thirty days. After this period the extract inhibited the activity of the AChE in the cerebellum and cerebral cortex of the rats in the DS group (P<0.05 as, compared to TS. In the striatum there was a significant increase in the activity of the AChE in rats of the TS group (P<0.01 when compared to the C group, and in the hippocampus there was no significant variation. These results indicate that the bark extract of "Jambolão"has an inhibitory effect on AChE in the cerebellum and cerebral cortex and an stimulatory effect on striatum, indicating a possible alteration in the functionality of the cholinergic system in such cerebral structures.

  12. Glucose-6-phosphate dehydrogenase and glutathione reductase activity in methemoglobin reduction by methylene blue and cyst amine: study on glucose-6-phosphate dehydrogenase-deficient individuals, on normal subjects and on riboflavin-treated subjects

    Directory of Open Access Journals (Sweden)

    Benedito Barraviera

    1988-10-01

    Full Text Available The authors have standardized methods for evaluation of the activity of the glucose-6-phosphate dehydrogenase and of glutathione reductase. The general principle of the first method was based on methemoglobin formation by sodium nitrite followed by stimulation of the glucose-6-phosphate dehydrogenase with methylene blue. Forty six adults (23 males and 23 females were studied. Subjects were not G6PD deficient and were aged 20 to 30 years. The results showed that methemoglobin reduction by methylene blue was 154.40 and 139.90 mg/min (p<0.05 for males and females, respectively, in whole blood, and 221.10 and 207.85 mg/min (n.s., respectively, in washed red cells. These data showed that using washed red cells and 0.7g% sodium nitrite concentration produced no differences between sexes and also shortened reading time for the residual amount of methemoglobin to 90 minutes. Glutathione reductase activity was evaluated on the basis of the fact that cystamine (a thiol agent binds to the SH groups of hemoglobin, forming complexes. These complexes are reversed by the action of glutathione reductase, with methemoglobin reduction occurring simultaneously with this reaction. Thirty two adults (16 males and 16 females were studied. Subjects were not G6PD deficient and were aged 20 to 30 years. Methemoglobin reduction by cystamine was 81.27 and 91.13 mg/min (p<0.01 for males and females, respectively. These data showed that using washed red cells and 0.1 M cystamine concentration permits a reading of the residual amount of methemoglobin at 180 minutes of incubation. Glutathione reductase activity was evaluated by methemoglobin reduction by cystamine in 14 females before and after treatment with 10 mg riboflavin per day for 8 days. The results were 73.69 and 94.26 jug/min (p<0.01 before and after treatment, showing that riboflavin treatment increase glutathione reductase activity even in normal individuals. Three Black G6PD-deficient individuals (2 males and 1

  13. Challenging the Ideology of Normal in Schools

    Science.gov (United States)

    Annamma, Subini A.; Boelé, Amy L.; Moore, Brooke A.; Klingner, Janette

    2013-01-01

    In this article, we build on Brantlinger's work to critique the binary of normal and abnormal applied in US schools that create inequities in education. Operating from a critical perspective, we draw from Critical Race Theory, Disability Studies in Education, and Cultural/Historical Activity Theory to build a conceptual framework for…

  14. Thrombin activatable fibrinolysis inhibitor (TAFI) - A possible link between coagulation and complement activation in the antiphospholipid syndrome (APS).

    Science.gov (United States)

    Grosso, Giorgia; Vikerfors, Anna; Woodhams, Barry; Adam, Mariette; Bremme, Katarina; Holmström, Margareta; Ågren, Anna; Eelde, Anna; Bruzelius, Maria; Svenungsson, Elisabet; Antovic, Aleksandra

    2017-10-01

    Thrombosis and complement activation are pathogenic features of antiphospholipid syndrome (APS). Their molecular link is Plasma carboxypeptidase-B, also known as thrombin activatable fibrinolysis inhibitor (TAFIa), which plays a dual role: anti-fibrinolytic, by cleaving carboxyl-terminal lysine residues from partially degraded fibrin, and anti-inflammatory, by downregulating complement anaphylatoxins C3a and C5a. To investigate the levels of TAFI (proenzyme) and TAFIa (active enzyme) in relation to complement activation, fibrin clot permeability and fibrinolytic function in clinical and immunological subsets of 52 APS patients and 15 controls. TAFI (pAPS patients compared to controls. Furthermore, TAFIa was increased (pAPS patients affected by arterial thrombosis compared to other APS-phenotypes. Positive associations were found between TAFI and age, fibrinogen and C5a, and between TAFIa and age, fibrinogen and thrombomodulin. TAFI and TAFIa levels were increased in patients with APS as a potential response to complement activation. Interestingly, TAFI activation was associated with arterial thrombotic APS manifestations. Thus, TAFIa may be considered a novel biomarker for arterial thrombosis in APS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Bicervical normal uterus with normal vagina | Okeke | Annals of ...

    African Journals Online (AJOL)

    To the best of our knowledge, only few cases of bicervical normal uterus with normal vagina exist in the literature; one of the cases had an anterior‑posterior disposition. This form of uterine abnormality is not explicable by the existing classical theory of mullerian anomalies and suggests that a complex interplay of events ...

  16. Group normalization for genomic data.

    Science.gov (United States)

    Ghandi, Mahmoud; Beer, Michael A

    2012-01-01

    Data normalization is a crucial preliminary step in analyzing genomic datasets. The goal of normalization is to remove global variation to make readings across different experiments comparable. In addition, most genomic loci have non-uniform sensitivity to any given assay because of variation in local sequence properties. In microarray experiments, this non-uniform sensitivity is due to different DNA hybridization and cross-hybridization efficiencies, known as the probe effect. In this paper we introduce a new scheme, called Group Normalization (GN), to remove both global and local biases in one integrated step, whereby we determine the normalized probe signal by finding a set of reference probes with similar responses. Compared to conventional normalization methods such as Quantile normalization and physically motivated probe effect models, our proposed method is general in the sense that it does not require the assumption that the underlying signal distribution be identical for the treatment and control, and is flexible enough to correct for nonlinear and higher order probe effects. The Group Normalization algorithm is computationally efficient and easy to implement. We also describe a variant of the Group Normalization algorithm, called Cross Normalization, which efficiently amplifies biologically relevant differences between any two genomic datasets.

  17. Group normalization for genomic data.

    Directory of Open Access Journals (Sweden)

    Mahmoud Ghandi

    Full Text Available Data normalization is a crucial preliminary step in analyzing genomic datasets. The goal of normalization is to remove global variation to make readings across different experiments comparable. In addition, most genomic loci have non-uniform sensitivity to any given assay because of variation in local sequence properties. In microarray experiments, this non-uniform sensitivity is due to different DNA hybridization and cross-hybridization efficiencies, known as the probe effect. In this paper we introduce a new scheme, called Group Normalization (GN, to remove both global and local biases in one integrated step, whereby we determine the normalized probe signal by finding a set of reference probes with similar responses. Compared to conventional normalization methods such as Quantile normalization and physically motivated probe effect models, our proposed method is general in the sense that it does not require the assumption that the underlying signal distribution be identical for the treatment and control, and is flexible enough to correct for nonlinear and higher order probe effects. The Group Normalization algorithm is computationally efficient and easy to implement. We also describe a variant of the Group Normalization algorithm, called Cross Normalization, which efficiently amplifies biologically relevant differences between any two genomic datasets.

  18. Comparison of spectrum normalization techniques for univariate ...

    Indian Academy of Sciences (India)

    Laser-induced breakdown spectroscopy; univariate study; normalization models; stainless steel; standard error of prediction. Abstract. Analytical performance of six different spectrum normalization techniques, namelyinternal normalization, normalization with total light, normalization with background along with their ...

  19. Normal people working in normal organizations with normal equipment: system safety and cognition in a mid-air collision.

    Science.gov (United States)

    de Carvalho, Paulo Victor Rodrigues; Gomes, José Orlando; Huber, Gilbert Jacob; Vidal, Mario Cesar

    2009-05-01

    A fundamental challenge in improving the safety of complex systems is to understand how accidents emerge in normal working situations, with equipment functioning normally in normally structured organizations. We present a field study of the en route mid-air collision between a commercial carrier and an executive jet, in the clear afternoon Amazon sky in which 154 people lost their lives, that illustrates one response to this challenge. Our focus was on how and why the several safety barriers of a well structured air traffic system melted down enabling the occurrence of this tragedy, without any catastrophic component failure, and in a situation where everything was functioning normally. We identify strong consistencies and feedbacks regarding factors of system day-to-day functioning that made monitoring and awareness difficult, and the cognitive strategies that operators have developed to deal with overall system behavior. These findings emphasize the active problem-solving behavior needed in air traffic control work, and highlight how the day-to-day functioning of the system can jeopardize such behavior. An immediate consequence is that safety managers and engineers should review their traditional safety approach and accident models based on equipment failure probability, linear combinations of failures, rules and procedures, and human errors, to deal with complex patterns of coincidence possibilities, unexpected links, resonance among system functions and activities, and system cognition.

  20. Normalization as a canonical neural computation

    Science.gov (United States)

    Carandini, Matteo; Heeger, David J.

    2012-01-01

    There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

  1. Normal matter storage of antiprotons

    International Nuclear Information System (INIS)

    Campbell, L.J.

    1987-01-01

    Various simple issues connected with the possible storage of anti p in relative proximity to normal matter are discussed. Although equilibrium storage looks to be impossible, condensed matter systems are sufficiently rich and controllable that nonequilibrium storage is well worth pursuing. Experiments to elucidate the anti p interactions with normal matter are suggested. 32 refs

  2. The N'ormal Distribution

    Indian Academy of Sciences (India)

    An optimal way of choosing sample size in an opinion poll is indicated using the normal distribution. Introduction. In this article, the ubiquitous normal distribution is intro- duced as a convenient approximation for computing bino- mial probabilities for large values of n. Stirling's formula. • and DeMoivre-Laplace theorem ...

  3. Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis

    NARCIS (Netherlands)

    von Lindern, M.; Deiner, E. M.; Dolznig, H.; Parren-van Amelsvoort, M.; Hayman, M. J.; Mullner, E. W.; Beug, H.

    2001-01-01

    Primary erythroid progenitors can be expanded by the synergistic action of erythropoietin (Epo), stem cell factor (SCF) and glucocorticoids. While Epo is required for erythropoiesis in general, glucocorticoids and SCF mainly contribute to stress erythropoiesis in hypoxic mice. This ability of normal

  4. Complete Normal Ordering 1: Foundations

    CERN Document Server

    Ellis, John; Skliros, Dimitri P.

    2016-01-01

    We introduce a new prescription for quantising scalar field theories perturbatively around a true minimum of the full quantum effective action, which is to `complete normal order' the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all `cephalopod' Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of `complete normal ordering' (which is an extension of the standard field theory definition of normal ordering) reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative i...

  5. The normal and pathological language

    OpenAIRE

    Espejo, Luis D.

    2014-01-01

    The extraordinary development of normal and pathological psychology has achieved in recent decades, thanks to the dual method of objective observation and oral survey enabled the researcher spirit of neuro-psychiatrist penetrate the intimate mechanism of the nervous system whose supreme manifestation is thought. It is normal psychology explaining the complicated game of perceptions: their methods of transmission, their centers of projection, its transformations and its synthesis to construct ...

  6. Is normal science good science?

    Directory of Open Access Journals (Sweden)

    Adrianna Kępińska

    2015-09-01

    Full Text Available “Normal science” is a concept introduced by Thomas Kuhn in The Structure of Scientific Revolutions (1962. In Kuhn’s view, normal science means “puzzle solving”, solving problems within the paradigm—framework most successful in solving current major scientific problems—rather than producing major novelties. This paper examines Kuhnian and Popperian accounts of normal science and their criticisms to assess if normal science is good. The advantage of normal science according to Kuhn was “psychological”: subjective satisfaction from successful “puzzle solving”. Popper argues for an “intellectual” science, one that consistently refutes conjectures (hypotheses and offers new ideas rather than focus on personal advantages. His account is criticized as too impersonal and idealistic. Feyerabend’s perspective seems more balanced; he argues for a community that would introduce new ideas, defend old ones, and enable scientists to develop in line with their subjective preferences. The paper concludes that normal science has no one clear-cut set of criteria encompassing its meaning and enabling clear assessment.

  7. nth roots of normal contractions

    International Nuclear Information System (INIS)

    Duggal, B.P.

    1992-07-01

    Given a complex separable Hilbert space H and a contraction A on H such that A n , n≥2 some integer, is normal it is shown that if the defect operator D A = (1 - A * A) 1/2 is of the Hilbert-Schmidt class, then A is similar to a normal contraction, either A or A 2 is normal, and if A 2 is normal (but A is not) then there is a normal contraction N and a positive definite contraction P of trace class such that parallel to A - N parallel to 1 = 1/2 parallel to P + P parallel to 1 (where parallel to · parallel to 1 denotes the trace norm). If T is a compact contraction such that its characteristics function admits a scalar factor, if T = A n for some integer n≥2 and contraction A with simple eigen-values, and if both T and A satisfy a ''reductive property'', then A is a compact normal contraction. (author). 16 refs

  8. Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator

    Energy Technology Data Exchange (ETDEWEB)

    Tromholt, N.; Hesse, B. (Hilleroed County Hospital (Denmark). Dept. of Clinical Physiology); Folkenborg, O. (Isotope-Pharmcy, Broenshoej (Denmark)); Selmer, J. (Novo Industri A/S, Bagsvaerd (Denmark)); Nielsen, N.T. (Hilleroed County Hospital (Denmark). Dept. of Radiology)

    1991-05-01

    The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i.e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75-85 MBq {sup 111}In-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies. (orig.).

  9. Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator

    International Nuclear Information System (INIS)

    Tromholt, N.; Hesse, B.; Selmer, J.; Nielsen, N.T.

    1991-01-01

    The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i.e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75-85 MBq 111 In-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies. (orig.)

  10. Influence of gamma-radiation on the biological activity of snake venoms in Peru

    International Nuclear Information System (INIS)

    Yarleque Ch, A.

    1986-03-01

    Effects of Co-60 gamma radiation on enzymatic, haemorragic an